AUTHOR OF THIS BLOG

DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER

Sun Pharma and Merck & Co. Inc. Enter into Licensing Agreement for Tildrakizumab

 Uncategorized  Comments Off on Sun Pharma and Merck & Co. Inc. Enter into Licensing Agreement for Tildrakizumab
May 052016
 

Tildrakizumab (MK-3222)

Company Merck & Co. Inc.
Description Anti-IL-23 antibody
Molecular Target Interleukin-23 (IL-23)
Mechanism of Action Antibody
Therapeutic Modality Biologic: Antibody
Latest Stage of Development Phase III
Standard Indication Psoriasis
Indication Details Treat moderate to severe chronic plaque psoriasis
Regulatory Designation
Partner Sun Pharmaceutical Industries Ltd.

 

 

 

Tildrakizumab is a monoclonal antibody designed for the treatment of immunologically mediated inflammatory disorders.[1]

Tildrakizumab was designed to block interleukin-23, a cytokine that plays an important role in managing the immune system and autoimmune disease. Originally developed by Schering-Plough, this drug is now part of Merck‘s clinical program, following that company’s acquisition of Schering-Plough.

Sun Pharmaceutical acquired worldwide rights to tildrakizumab for use in all human indications from Merck in exchange for an upfront payment of U.S. $80 million. Upon product approval, Sun Pharmaceutical will be responsible for regulatory activities, including subsequent submissions, pharmacovigilance, post approval studies, manufacturing and commercialization of the approved product. [2]

As of March 2014, the drug was in phase III clinical trials for plaque psoriasis. The two trials will enroll a total of nearly 2000 patients, and preliminary results are expected in June, 2015. [3][4]

References

 

http://clinicaltrials.gov/ct2/show/NCT01722331?term=SCH-900222&phase=2&fund=2&rank=2

 

Sun Pharma and Merck & Co. Inc. Enter into Licensing Agreement for Tildrakizumab, MK 3222

WHITEHOUSE STATION, N.J., and MUMBAI, India, Wednesday, September 17, 2014 (BUSINESS WIRE) – Merck & Co., Inc., (NYSE:MRK), known as MSD outside the United States and Canada, and Sun Pharmaceutical Industries Ltd. (Reuters: SUN.BO, Bloomberg: SUNP IN, NSE: SUNPHARMA, BSE: 524715) through their respective subsidiaries, today announced an exclusive worldwide licensing agreement for Merck’s investigational therapeutic antibody candidate, tildrakizumab, (MK-3222), which is currently being evaluated in Phase 3 registration trials for the treatment of chronic plaque psoriasis, a skin ailment.

Under terms of the agreement, Sun Pharma will acquire worldwide rights to tildrakizumab for use in all human indications from Merck in exchange for an upfront payment of U.S. $80 million. Merck will continue all clinical development and regulatory activities, which will be funded by Sun Pharma. Upon product approval, Sun Pharma will be responsible for regulatory activities, including subsequent submissions, pharmacovigilance, post approval studies, manufacturing and commercialization of the approved product. Merck is eligible to receive undisclosed payments associated with regulatory (including product approval) and sales milestones, as well as tiered royalties ranging from mid-single digit through teen percentage rates on sales.

“Consistent with our previously announced global initiative to sharpen our commercial and R&D focus, including prioritizing our late stage pipeline candidates, we are pleased to enter into this agreement with Sun Pharma to help realize the potential of tildrakizumab for patients with chronic plaque psoriasis,” said Iain D. Dukes, Ph.D., senior vice president, Business Development and Licensing, Merck Research Laboratories.

“Sun Pharma is very pleased to enter into this collaboration with Merck, a recognized leader in the field of inflammatory/immunology therapies, for this late-stage candidate for chronic plaque psoriasis,” said Kirti Ganorkar, senior vice president, Business Development, Sun Pharma. “This collaboration is a part of our strategy towards building our pipeline of innovative dermatology products in a market with strong growth potential.”

The transaction is subject to customary closing conditions, including the requirements under the Hart Scott-Rodino Antitrust Improvements Act.

About Tildrakizumab

Tildrakizumab is an investigational humanized, anti-IL-23p19 monoclonal antibody that binds specifically to IL-23p19 and is therefore designed to selectively block the cytokine IL-23. Human genetics suggest that inhibiting IL-23 is effective for treating inflammatory conditions. In clinical studies for the treatment of chronic plaque psoriasis, tildrakizumab demonstrates efficacy in blocking inflammation by blocking IL-23. Other potential indications, which may be evaluated in future, include psoriatic arthritis and Crohn’s Disease.

Further details of the Phase 3 clinical trials can be found at: http://clinicaltrials.gov

About Merck

Today’s Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

About Sun Pharma

Established in 1983, listed since 1994 and headquartered in India, Sun Pharmaceutical Industries Ltd. (Reuters: SUN.BO, Bloomberg: SUNP IN, NSE: SUNPHARMA, BSE: 524715) is an international specialty pharmaceutical company with over 75% sales from global markets. It manufactures and markets a large basket of pharmaceutical formulations as branded generics as well as generics in US, India and several other markets across the world. For the year ending March 2014, overall revenues were at US$2.7 billion, of which US contributed US$1.6 billion. In India, the company is a leader in niche therapy areas of psychiatry, neurology, cardiology, nephrology, gastroenterology, orthopedics and ophthalmology. The company has strong skills in product development, process chemistry, and manufacturing of complex dosage forms. More information about the company can be found at www.sunpharma.com.

Tildrakizumab
Monoclonal antibody
Type ?
Source Humanized (from mouse)
Target IL23
Identifiers
CAS Number 1326244-10-3
ATC code none
ChemSpider none
Chemical data
Formula C6426H9918N1698O2000S46
Molar mass 144.4 kg/mol

///////Sun Pharma, Merck & Co. Inc, Licensing Agreement, Tildrakizumab, mk 3222

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GDC-0919; NLG-919; RG-6078

 Uncategorized  Comments Off on GDC-0919; NLG-919; RG-6078
Apr 052016
 

img
MF C18H22N2O
MW: 282.17321

GDC-0919; NLG-919; RG-6078, GDC0919; GDC-0919; GDC 0919; NLG919; NLG 919; NLG-919; RG6078; RG-6078; RG 6078.

 1-cyclohexyl-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethanol
CAS No.1402836-58-1

GDC-0919, also known as NLG919 and RG6078, is an orally available inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), with potential immunomodulating and antineoplastic activities. Upon administration, NLG919 targets and binds to IDO1, a cytosolic enzyme responsible for the oxidation of the essential amino acid tryptophan into kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, this agent increases tryptophan levels, restores the proliferation and activation of various immune cells, including dendritic cells (DCs), natural killer (NK) cells, T-lymphocytes, and causes a reduction in tumor-associated regulatory T-cells (Tregs). Activation of the immune system, which is suppressed in many cancers, may induce a cytotoxic T-lymphocyte (CTL) response against the IDO1-expressing tumor cells

  • Originator Lankenau Institute for Medical Research
  • Developer Genentech; NewLink Genetics Corporation
  • Class Antineoplastics; Small molecules
  • Mechanism of Action Immunomodulators; Indoleamine-pyrrole 2,3-dioxygenase inhibitors

Phase I Solid tumours

Patent ID Date Patent Title
US2015210769 2015-07-30 ANTIBODY MOLECULES TO PD-1 AND USES THEREOF
US2014066625 2014-03-06 Fused Imidazole Derivatives Useful as IDO Inhibitors
  • 27 Sep 2015 Pharmacokinetics results from a phase-I clinical trial in Solid tumours presented at the European Cancer Congress 2015 (ECC-2015)
  • 27 Sep 2015 Positive efficacy and safety results from a phase-I clinical trial in Solid tumours presented at the European Cancer Congress 2015 (ECC-2015)
  • 31 Jul 2015 Phase-I clinical trials in Solid tumours (Combination therapy, Late-stage disease, Second-line therapy or greater) in USA (PO) (NCT02471846)

 

PATENT

http://www.google.com/patents/WO2012142237A1?cl=en

str1

PATENT

US-20160002249-A1 / 2016-01-07

Fused Imidazole Derivatives Useful as IDO Inhibitors

1304Image loading...1-cyclohexyl-2-(5H-imidazo[5,1- a]isoindol-5-yl)ethanol79 1H NMR (a mixture of diastereomers) 1.10-1.37 (m, 6H), 1.66-1.80 (m, 5H), 2.05 (m, 2H), 2.15 (m, 1H), 3.72 (m, 1H), 5.36 and 5.46 (two m, 1H), 7.16 (s, 1H), 7.25 (m, 1H), 7.34 (m, 1H), 7.43 (d, 1H, J = 7.6 Hz), 7.54 (d, 1H, J = 7.6 Hz), 7.80 (s, 1H)

 

 

 

WO2011056652A1 * Oct 27, 2010 May 12, 2011 Newlink Genetics Imidazole derivatives as ido inhibitors
WO2012142237A1 * Apr 12, 2012 Oct 18, 2012 Newlink Geneticks Corporation Fused imidazole derivatives useful as ido inhibitors
WO2014159248A1 Mar 10, 2014 Oct 2, 2014 Newlink Genetics Corporation Tricyclic compounds as inhibitors of immunosuppression mediated by tryptophan metabolization
US8722720 Oct 27, 2010 May 13, 2014 Newlink Genetics Corporation Imidazole derivatives as IDO inhibitors
US9260434 Oct 14, 2013 Feb 16, 2016 Newlink Genetics Corporation Fused imidazole derivatives useful as IDO inhibitors
US20140066625 * Oct 14, 2013 Mar 6, 2014 Newlink Genetics Corporation Fused Imidazole Derivatives Useful as IDO Inhibitors
US20160002249 * Jul 8, 2015 Jan 7, 2016 Newlink Genetics Corporation Fused Imidazole Derivatives Useful as IDO Inhibitors

REFERENCES

Nature Reviews Drug Discovery14,373(2015)doi:10.1038/nrd4658

http://www.ncbi.nlm.nih.gov/pubmed/21517759

http://www.roche.com/irp150128-annex.pdf

/////CRD1152, CRD 1152, CRD-1152, Curadev,  Research Collaboration, Licensing Agreement, Develop,  Cancer Immunotherapeutic, IDO1 and TDO inhibitors

img

OC(C1CCCCC1)CC(C2=C3C=CC=C2)N4C3=CN=C4

 

 

 

 

 

/////GDC-0919; NLG-919; RG-6078

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AUNP-12 from Aurigene Discovery Technologies Limited

 Uncategorized  Comments Off on AUNP-12 from Aurigene Discovery Technologies Limited
Apr 042016
 

 

 

AUNP-12

AUR-012; Aurigene-012; NP-12, Aurigene; PD-1 inhibitor peptide (cancer), Aurigene; PD-1 inhibitor peptide (cancer), Aurigene/ Pierre Fabre; W-014A

 

Company Aurigene Discovery Technologies Ltd.
Description A programmed cell death 1 (PDCD1; PD-1; CD279) peptide antagonist
Molecular Target Programmed cell death 1 (PD-1) (PDCD1) (CD279)
Mechanism of Action Programmed cell death 1 (PD-1) antagonist
Therapeutic Modality Peptide
Latest Stage of Development Preclinical
Standard Indication Cancer (unspecified)
Indication Details Treat cancer
Regulatory Designation
Partner Laboratoires Pierre Fabre S.A.

Aurigene Discovery Technologies Limited

INNOVATOR

 

 

  • Programmed Cell Death 1 or PD-1 (also referred to as PDCD1) is a 50 to 55 kD type I membrane glycoprotein (Shinohara T et al, Genomics, 1994, Vol. 23, No. 3, pp. 704-706). PD-1 is a receptor of the CD28 superfamily that negatively regulates T cell antigen receptor signalling by interacting with the specific ligands and is suggested to play a role in the maintenance of self tolerance.
  • PD-1 peptide relates to almost every aspect of immune responses including autoimmunity, tumour immunity, infectious immunity, transplantation immunity, allergy and immunological privilege.
  • The PD-1 protein’s structure comprise of—

      • an extracellular IgV domain followed by
      • a transmembrane region and
      • an intracellular tail
  • The intracellular tail contains two phosphorylation sites located in an immunoreceptor tyrosine-based inhibitory motif and an immunoreceptor tyrosine-based switch motif, which suggests that PD-1 negatively regulates TCR signals. Also, PD-1 is expressed on the surface of activated T cells, B cells, and macrophages, (Y. Agata et al., Int Immunol 8, 765, May 1996) suggesting that compared to CTLA-4 ((Cytotoxic T-Lymphocyte Antigen 4, also known as CD152 (Cluster of differentiation 152) is a protein that also plays an important regulatory role in the immune system), PD-1 more broadly negatively regulates immune responses.
  • PD-1 has two ligands, PD-L1 (Programmed Death Ligand for PDCD1L1 or B7-H1) (Freeman G J et al, Journal of Experimental Medicine, 2000, Vol. 19, No. 7, pp. 1027-1034) and PD-L2 (Programmed Death Ligand 2 or PDCD1L2 or B7-DC) (Latchman Y et al, Nature Immunology, 2001, Vol. 2, No. 3, pp. 261-267), which are members of the B7 family. PD-L1 is known to be expressed not only in immune cells, but also in certain kinds of tumour cell lines (such as monocytic leukaemia-derived cell lines, mast cell tumour-derived cell lines, hematoma-derived cell lines, neuroblastoma-derived cell lines, and various mammary tumour-derived cell lines) and in cancer cells derived from diverse human cancer tissues (Latchman Y et al, Nature Immunology, 2001, Vol. 2, No. 3, pp. 261-267) and on almost all murine tumour cell lines, including PA1 myeloma, P815 mastocytoma, and B16 melanoma upon treatment with IFN-γ (Y. Iwai et al., Proc Natl Acad Sci USA 99, 12293, Sep. 17, 2002 and C. Blank et al., Cancer Res 64, 1140, February, 2004). Similarly PD-L2 expression is more restricted and is expressed mainly by dendritic cells and a few tumour cell lines. PD-L2 expression has been verified in Hodgkin’s lymphoma cell lines and others. There is a hypothesis that some of the cancer or tumour cells take advantage from interaction between PD-1 and PD-L1 or PD-L2, for suppressing or intercepting T-cell immune responses to their own (Iwai Y et al, Proceedings of the National Academy of Science of the United States of America, 2002, Vol. 99, No. 19, pp. 12293-12297).
  • Tumour cells and virus (including HCV and HIV) infected cells are known to express the ligand for PD-1 (to create Immunosuppression) in order to escape immune surveillance by host T cells. It has been reported that the PD-1 gene is one of genes responsible for autoimmune diseases like systemic lupus erythematosis (Prokunina et al, Nature Genetics, 2002, Vol. 32, No. 4, 666-669). It has also been indicated that PD-1 serves as a regulatory factor for the onset of autoimmune diseases, particularly for peripheral self-tolerance, on the ground that PD-1-deficient mice develop lupus autoimmune diseases, such as glomerulonephritis and arthritis (Nishimura H et al, International Immunology, 1998, Vol. 10, No. 10, pp. 1563-1572; Nishimura H et al, Immunity, 1999, Vol. 11, No. 2, pp. 141-151), and dilated cardiomyopathy-like disease (Nishimura H et al, Science, 2001, Vol. 291, No. 5502, pp. 319-332).
  • Hence, in one approach, blocking the interaction of PD-1 with its ligand (PD-L1, PD-L2 or both) may provide an effective way for specific tumour and viral immunotherapy.
  • Wood et al in U.S. Pat. No. 6,808,710 discloses method for down modulating an immune response comprising contacting an immune cell expressing PD-1 with an antibody that binds to PD-1, in multivalent form, such that a negative signal is transduced via PD-1 to thereby down modulate the immune response. Such an antibody may be a cross-linked antibody to PD-1 or an immobilized antibody to PD-1.
  • Freeman et al in U.S. Pat. No. 6,936,704 and its divisional patent U.S. Pat. No. 7,038,013 discloses isolated nucleic acids molecules, designated B7-4 nucleic acid molecules, which encode novel B7-4 polypeptides, isolated B7-4 proteins, fusion proteins, antigenic peptides and anti-B7-4 antibodies, which co-stimulates T cell proliferation in vitro when the polypeptide is present on a first surface and an antigen or a polyclonal activator that transmits an activating signal via the T-cell receptor is present on a second, different surface.
  • There are some reports regarding substances inhibiting immunosuppressive activity of PD-1, or interaction between PD-1 and PD-L1 or PD-L2, as well as the uses thereof. A PD-1 inhibitory antibody or the concept of a PD-1 inhibitory peptide is reported in WO 01/14557, WO 2004/004771, and WO 2004/056875. On the other hand, a PD-L1 inhibitory antibody or a PD-L1 inhibitory peptide is reported in WO 02/079499, WO 03/042402, WO 2002/086083, and WO 2001/039722. A PD-L2 inhibitory antibody or a PD-L2 inhibitory peptide is reported in WO 03/042402 and WO 02/00730.
  • WO2007005874 describes isolated human monoclonal antibodies that specifically bind to PD-L1 with high affinity. The disclosure provides methods for treating various diseases including cancer using anti-PD-L1 antibodies.
  • US2009/0305950 describes multimers, particularly tetramers of an extracellular domain of PD-1 or PD-L1. The application describes therapeutic peptides.
  • Further, the specification mentions that peptides can be used therapeutically to treat disease, e.g., by altering co-stimulation in a patient. An isolated B7-4 or PD-1 protein, or a portion or fragment thereof (or a nucleic acid molecule encoding such a polypeptide), can be used as an immunogen to generate antibodies that bind B7-4 or PD-1 using standard techniques for polyclonal and monoclonal antibody preparation. A full-length B7-4 or PD-1 protein can be used, or alternatively, the invention provides antigenic peptide fragments of B7-4 or PD-1 for use as immunogens. The antigenic peptide of B7-4 or PD-1 comprises at least 8 amino acid residues and encompasses an epitope of B7-4 or PD-1 such that an antibody raised against the peptide forms a specific immune complex with B7-4 or PD-1. Preferably, the antigenic peptide comprises at least 10 amino acid residues, more preferably at least 15 amino acid residues, even more preferably at least amino acid residues, and most preferably at least 30 amino acid residues.
  • Freeman et al in U.S. Pat. No. 7,432,059 appears to disclose and claim methods of identifying compounds that up modulate T cell activation in the presence of a PD-1-mediated signal. Diagnostic and treatment methods utilizing compositions of the invention are also provided in the patent.
  • Further, Freeman et al in U.S. Pat. No. 7,709,214 appears to cover methods for up regulating an immune response with agents that inhibit the interactions between PD-L2 and PD-1.
  • Despite existence of many disclosures as discussed above, however, a significant unmet medical need still exists due to the lack of effective peptides or modified peptides as therapeutic agents as alternatives in the therapeutic area. It is known that synthetic peptides offer certain advantages over antibodies such as ease of production with newer technologies, better purity and lack of contamination by cellular materials, low immunogenicity, improved potency and specificity. Peptides may be more stable and offer better storage properties than antibodies. Moreover, often peptides possess better tissue penetration in comparison with antibodies, which could result in better efficacy. Peptides can also offer definite advantages over small molecule therapeutics counterparts such as lesser degree of toxicity and lower probability of drug-drug interaction.
  • The present invention therefore may provide the solution for this unmet medical need by offering novel synthetic peptide and its derivatives which are based on the PD1 ectodomain.

09338-scitech1-NovartisAcxd
Aurigene team: (from left) Brahma Reddy V, Thomas Antony, Murali Ramachandra, Venkateshwar Rao G, Wesley Roy Balasubramanian, Kishore Narayanan, Samiulla DS, Aravind AB, and Shekar Chelur

 

 

Patent

http://www.google.com/patents/US20110318373

8. SNTSESFK(SNTSESF)FRVTQLAPKAQIKE-NH2 (SEQ ID NO: 49)

 

Example 2 Synthesis of

Synthesis of Linear Fragment—Fmoc-FRVTQLAPKAQIKE

  • Desiccated CLEAR-Amide resin ((100-200 mesh) 0.4 mmol/g, 0.5 g) was distributed in 2 polyethylene vessels equipped with a polypropylene filter. The linear peptide synthesis on solid phase were carried out automatically, using Symphony parallel synthesizer (PTI) using the synthesis programs mentioned in the table below. Swelling, C-terminal amino acid [Fmoc-Glu(OtBu)-OH] attachment and capping of the peptidyl resin was carried out as per the protocol in Table I. Subsequent amino acid coupling was carried out as mentioned in Table II. The amino acids used in the synthesis were Fmoc Phe-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Val-OH, Fmoc-Thr(OtBu)-OH, Fmoc-Gln(Trt)-OH, Fmoc-Lys(Boc)-OH, Fmoc-Leu-OH, Fmoc-Ala-OH, Fmoc-Pro-OH, Fmoc-Ile-OH. After the completion of Fmoc-Phe-OH coupling the resin was taken out form peptide synthesiser and manual coupling was carried out as follows
  • Fmoc-Phe-OH peptidyl resin from automated synthesiser was pooled in to a glass vessel with frit. The Fmoc group of the peptidyl resin was deprotected by treating it twice with 20% (v/v) piperidine/DMF solution for 5 and 15 min (10 m L). The resin was washed with DMF (6×15 m L), DCM (6×15 m L) and DMF (6×15 m L). Kaiser test on peptide resin aliquot upon completion of Fmoc-deprotection was positive. Fmoc-Lys (Fmoc)-OH (0.48 g; 4 equiv. 0.8 m mol) in dry DMF was added to the deprotected resin and coupling was initiated with DIC (0.15 m L; 5 equiv, 1 m mol) and HOBT (0.08 g; 5 equiv, 0.6 m mol) in DMF. The concentration of each reactant in the reaction mixture was approximately 0.4 M. The mixture was rotated on a rotor at room temperature for 3 h. Resin was filtered and washed with DMF (6×15 mL), DCM (6×15 mL) and DMF (6×15 mL). Kaiser test on peptide resin aliquot upon completion of coupling was negative. The Fmoc group on the peptidyl resin is deprotected by treating it twice with 20% (v/v) piperidine/DMF solution for 5 and 15 min (15 mL). The resin was washed with DMF (6×15 mL), DCM (6×15 mL) and DMF (6×15 mL). Kaiser test on peptide resin aliquot upon completion of Fmoc-deprotection was positive. After the deprotection of Fmoc group on Fmoc-Lys(Fmoc)-attached peptidyl resin the peptide chain growth was carried out from both the free amino terminus suing 8 equivalent excess of amino acid (1.6 m mol, 8 equivalent excess of HOBt (0.22 g, 1.6 m mol) and 10 equivalent excess of DIC (0.32 m L, 2 m mol) relative to resin loading. The coupling was carried out at room temperature for 3 h. The amino acids coupled to the peptidyl resin were; Fmoc-Phe-OH (0.62 g; 8 equiv, 1.6 m mol), Fmoc-Ser (OtBu)-OH (0.62 g; 8 equiv, 1.6 m mol), Fmoc-Glu (OtBu)-OH (0.68 g; 8 equiv, 1.6 m mol), Fmoc-Ser (OtBu)-OH (0.62 g; 8 equiv, 1.6 m mol), Fmoc-Thr (OtBu)-OH (0.64 g; 8 equiv, 1.6 m mol), Fmoc-Asn (Trt)-OH (0.95 g; 8 equiv, 1.6 m mol) and N-terminus amino acids as Boc-Ser (OtBu)-OH (0.41 g; 8 equiv, 1.6 m mol) The peptidyl resin was cleaved as mentioned in procedure for cleavage using cleavage cocktail A to yield (565 mg), 70% yield. The crude material was purified by preparative HPLC on Zorbax Eclipse XDB-C18 column (9.4 mm×250 mm, 5 μm) with buffer A: 0.1% TFA/Water, buffer B: Acetonitrile. The peptide was eluted by gradient elution 0-5 min=5-10% buffer B, 10-20 min=29% buffer B with a flow rate of 7 mL/min. HPLC: (method 1): RT-12 min (96%); LCMS Calculated Mass: 3261.62, Observed Mass: 1631.6 [M/2+H]+; 1088 [M/3+H]+); 816.2[M/4+H]+;

STRUCTURE , READER DISCRETION IS NEEDED

aunf12

N2,N6-Bis(L-seryl-L-asparaginyl-L-threonyl-L-seryl-L-alpha-glutamyl-L-seryl-L-phenylalanyl)-L-lysyl-L-phenylalanyl-L-arginyl-L-valyl-L-threonyl-L-glutaminyl-L-leucyl-L-alanyl-L-prolyl-L-lysyl-L-alanyl-L-glutaminyl-L-isoleucyl-L-lysyl-L-alpha-glutamine

C142 H226 N40 O48, 3261.553

 CAS 1353563-85-5,
L-​α-​Glutamine, N2,​N6– ​bis(L-​seryl-​L-​asparaginyl-​L-​threonyl-​L-​seryl-​L-​α-​glutamyl-​L- ​seryl-​L-​phenylalanyl)​-​L-​lysyl-​L-​phenylalanyl-​L-​arginyl-​L-​ valyl-​L-​threonyl-​L-​glutaminyl-​L-​leucyl-​L-​alanyl-​L-​prolyl-​L-​ lysyl-​L-​alanyl-​L-​glutaminyl-​L-​isoleucyl-​L-​lysyl-

aunf12

aunf12

SEE ALSO

CAS 1353564-61-0,
L-​α-​Glutamine, N2,​N6– ​bis(D-​seryl-​L-​asparaginyl-​L-​threonyl-​L-​seryl-​L-​α-​glutamyl-​L- ​seryl-​L-​phenylalanyl)​-​L-​lysyl-​L-​phenylalanyl-​L-​arginyl-​L-​ valyl-​L-​threonyl-​L-​glutaminyl-​L-​leucyl-​L-​alanyl-​L-​prolyl-​L-​ lysyl-​L-​alanyl-​L-​glutaminyl-​L-​isoleucyl-​L-​lysyl-
 CAS 1353563-91-3
D-​α-​Glutamine, N2,​N6– ​bis(D-​seryl-​D-​asparaginyl-​D-​threonyl-​D-​seryl-​D-​α-​glutamyl-​D- ​seryl-​D-​phenylalanyl)​-​D-​lysyl-​D-​phenylalanyl-​D-​arginyl-​D-​ valyl-​D-​threonyl-​D-​glutaminyl-​D-​leucyl-​D-​alanyl-​D-​prolyl-​D-​ lysyl-​D-​alanyl-​D-​glutaminyl-​D-​isoleucyl-​D-​lysyl-

US 2015087581

Compound 8 (SEQ ID NO: 49) SNTSESFK(SNTSESF)FRVTQLAPKAQIKE-NH2Image loading...

Example 2Synthesis of Sequence Shown in SEQ ID NO: 49

Image loading...

Synthesis of Linear Fragment—Fmoc-FRVTQLAPKAQIKE

Desiccated CLEAR-Amide resin ((100-200 mesh) 0.4 mmol/g, 0.5 g) was distributed in 2 polyethylene vessels equipped with a polypropylene filter. The linear peptide synthesis on solid phase were carried out automatically, using Symphony parallel synthesizer (PTI) using the synthesis programs mentioned in the table below. Swelling, C-terminal amino acid [Fmoc-Glu(OtBu)-OH] attachment and capping of the peptidyl resin was carried out as per the protocol in Table I. Subsequent amino acid coupling was carried out as mentioned in Table II. The amino acids used in the synthesis were Fmoc Phe-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Val-OH, Fmoc-Thr(OtBu)-OH, Fmoc-Gln(Trt)-OH, Fmoc-Lys(Boc)-OH, Fmoc-Leu-OH, Fmoc-Ala-OH, Fmoc-Pro-OH, Fmoc-Ile-OH. After the completion of Fmoc-Phe-OH coupling the resin was taken out form peptide synthesiser and manual coupling was carried out as follows.

Fmoc-Phe-OH peptidyl resin from automated synthesiser was pooled in to a glass vessel with frit. The Fmoc group of the peptidyl resin was deprotected by treating it twice with 20% (v/v) piperidine/DMF solution for 5 and 15 min (10 mL). The resin was washed with DMF (6×15 mL), DCM (6×15 mL) and DMF (6×15 mL). Kaiser test on peptide resin aliquot upon completion of Fmoc-deprotection was positive.

Fmoc-Lys (Fmoc)-OH (0.48 g; 4 equiv. 0.8 mmol) in dry DMF was added to the deprotected resin and coupling was initiated with DIC (0.15 mL; 5 equiv, 1 mmol) and HOBT (0.08 g; 5 equiv, 0.6 mmol) in DMF. The concentration of each reactant in the reaction mixture was approximately 0.4 M. The mixture was rotated on a rotor at room temperature for 3 h. Resin was filtered and washed with DMF (6×15 mL), DCM (6×15 mL) and DMF (6×15 mL). Kaiser test on peptide resin aliquot upon completion of coupling was negative. The Fmoc group on the peptidyl resin is deprotected by treating it twice with 20% (v/v) piperidine/DMF solution for 5 and 15 min (15 mL). The resin was washed with DMF (6×15 mL), DCM (6×15 mL) and DMF (6×15 mL). Kaiser test on peptide resin aliquot upon completion of Fmoc-deprotection was positive.

After the deprotection of Fmoc group on Fmoc-Lys(Fmoc)-attached peptidyl resin the peptide chain growth was carried out from both the free amino terminus suing 8 equivalent excess of amino acid (1.6 mmol, 8 equivalent excess of HOBt (0.22 g, 1.6 mmol) and 10 equivalent excess of DIC (0.32 mL, 2 mmol) relative to resin loading. The coupling was carried out at room temperature for 3 h. The amino acids coupled to the peptidyl resin were; Fmoc-Phe-OH (0.62 g; 8 equiv, 1.6 mmol), Fmoc-Ser (OtBu)-OH (0.62 g; 8 equiv, 1.6 mmol), Fmoc-Glu (OtBu)-OH (0.68 g; 8 equiv, 1.6 mmol), Fmoc-Ser (OtBu)-OH (0.62 g; 8 equiv, 1.6 mmol), Fmoc-Thr (OtBu)-OH (0.64 g; 8 equiv, 1.6 mmol), Fmoc-Asn (Trt)-OH (0.95 g; 8 equiv, 1.6 m mol) and N-terminus amino acids as Boc-Ser (OtBu)-OH (0.41 g; 8 equiv, 1.6 mmol) The peptidyl resin was cleaved as mentioned in procedure for cleavage using cleavage cocktail A to yield (565 mg), 70% yield. The crude material was purified by preparative HPLC on Zorbax Eclipse XDB-C18 column (9.4 mm×250 mm, 5 μm) with buffer A: 0.1% TFA/Water, buffer B:Acetonitrile. The peptide was eluted by gradient elution 0-5 min=5-10% buffer B, 10-20 min=29% buffer B with a flow rate of 7 mL/min. HPLC: (method 1): RT—12 min (96%); LCMS Calculated Mass: 3261.62, Observed Mass: 1631.6 [M/2+H]+; 1088 [M/3+H]+;); 816.2[M/4+H]+.

SMILES

O=C(N[C@@H](CCCCNC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)N)[C@@H](C)O)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(N)=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)N)[C@@H](C)O

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CAS 1353564-65-4
C142 H226 N40 O48
L-​α-​Glutamine, L-​seryl-​L-​asparaginyl-​L-​threonyl-​L-​seryl-​L-​α-​glutamyl-​L-​seryl-​L-​phenylalanyl-​N6– ​(L-​seryl-​D-​asparaginyl-​L-​threonyl-​L-​seryl-​L-​α-​glutamyl-​L-​ seryl-​L-​phenylalanyl)​-​L-​lysyl-​L-​phenylalanyl-​L-​arginyl-​L-​ valyl-​L-​threonyl-​L-​glutaminyl-​L-​leucyl-​L-​alanyl-​L-​prolyl-​L-​ lysyl-​L-​alanyl-​L-​glutaminyl-​L-​isoleucyl-​L-​lysyl-
Molecular Weight, 3261.55

aunf12

NEXT……….

CAS 1353564-31-4, C142 H226 N40 O48
L-​α-​Glutamine, L-​seryl-​L-​asparaginyl-​L-​threonyl-​L-​seryl-​L-​α-​glutamyl-​L-​seryl-​L-​phenylalanyl-​N6– ​(D-​seryl-​D-​asparaginyl-​D-​threonyl-​D-​seryl-​D-​α-​glutamyl-​D-​ seryl-​D-​phenylalanyl)​-​L-​lysyl-​L-​phenylalanyl-​L-​arginyl-​L-​ valyl-​L-​threonyl-​L-​glutaminyl-​L-​leucyl-​L-​alanyl-​L-​prolyl-​L-​ lysyl-​L-​alanyl-​L-​glutaminyl-​L-​isoleucyl-​L-​lysyl-
USE ALL YOUR DISCRETION……………

Clips

Aurigene and Pierre Fabre Pharmaceuticals Announce a Licensing Agreement for a New Cancer Therapeutic in Immuno-oncology: AUNP12, an Immune Checkpoint Modulator Targeting the PD-1 Pathway

Pierre Fabre are thus reinforcing their oncology portfolio which already enjoys a combination of chemotherapies, monoclonal antibodies and immuno-conjugates assets at various development phases

Feb 13, 2014, 03:14 ET from Aurigene and Pierre Fabre Pharmaceuticals

CASTRES, France and BANGALORE, India, February 13, 2014 /PRNewswire/ —

Pierre Fabre, the third largest French pharmaceutical company, and Aurigene, a leading biotech company based in India, today announced that the two companies have entered into a collaborative license, development and commercialization agreement granting Pierre Fabre global Worldwide rights (excluding India) to a new immune checkpoint modulator, AUNP-12.

AUNP-12 offers a breakthrough mechanism of action in the PD-1 pathway compared to other molecules currently in development in the highly promising immune therapy cancer space. AUNP-12 is the only peptide therapeutic in this pathway and could offer more effective and safer combination opportunities with emerging and established treatment regimens.  AUNP-12 will be in development for numerous cancer indications.

Under the terms of this agreement, Aurigene will receive an upfront payment from Pierre Fabre. Aurigene will also receive additional milestone payments based upon the continued development, regulatory progresses and commercialization of AUNP-12.

“We are pleased that Pierre Fabre see the PD-1 program as a strategic asset in their portfolio. Overall, the deal structure, in line with the financial terms that have been seen in this space, demonstrate the importance that Pierre Fabre attach to the program,” said CSN Murthy, CEO, Aurigene.

“The plans that Pierre Fabre have detailed for the development of this differentiated asset highlight the long-term opportunities for this novel cancer therapeutic,” added Murali Ramachandra, Sr VP, Research, Aurigene.

“This agreement, in the field of oncology, is fully consistent with our vision to build Pierre Fabre’s future in prescription drugs, from a combination of cutting-edge internal R&D capabilities and license partnerships with innovative biotech companies like Aurigene,” stated Bertrand Parmentier, CEO, Pierre Fabre.

“With this deal, Pierre-Fabre Pharmaceuticals are reinforcing their portfolio of oncology assets and capitalizing on their proven capabilities in developing biological compounds such as monoclonal antibodies and immuno-conjugates. We have been impressed by the science at Aurigene and encouraged by the differentiated profile reported for AUNP-12,” added Frédéric Duchesne, President, Pierre Fabre Pharmaceuticals.

About immuno-oncology

Immuno-oncology is an emerging field in cancer therapy, where the body’s own immune system is harnessed to fight against cancer. This approach of targeting cancer through immune response has had a breakthrough when robust and sustained responses were obtained only upon blocking the immune checkpoint targets (such as PD-1 and CTLA4). Recent successes in clinical trials performed with such therapies suggest that immunotherapy should be considered alongside surgery, chemotherapy, radiotherapy and targeted therapy as the fifth cornerstone of cancer treatment.

PD-1 (Programmed cell Death 1) is a receptor that negatively regulates T-cell activation by interacting with specific ligands PD-L1 and PD-L2. Tumor cells express these ligands and thereby escape from the action of T-cells.

About AUNP-12

AUNP-12  is a branched 29-amino acid peptide sequence engineered from the PD-L1/ L2 binding domain of PD-1 It blocks the PD-1/PD-L1, PD-1/PD-L2 and PD-L1/CD80 pathways. AUNP-12 is highly effective in antagonizing PD-1 signaling, with desirable in vivo exposure upon subcutaneous dosing. It inhibits tumor growth and metastasis in preclinical models of cancer and is well tolerated with no overt toxicity at any of the tested doses.

About Aurigene

Aurigene is a biotech focused on development of innovative small molecule and peptide therapeutics for Oncology and Inflammation; key focus areas for Aurigene are Immuno-oncology, Epigenetics and the Th17 pathway. Aurigene’s PD-1 program is the first of several peptide-based immune checkpoint programs that are at different stages of Discovery.

Aurigene has partnered with several big pharma and mid-pharma companies in the US and Europe, and has delivered multiple clinical compounds through these partnerships. With over 500 scientists, Aurigene has collaborated with 6 of the top 10 pharma companies.

Aurigene’s pre-clinical pipeline includes (1) Selective and pan-BET Bromodomain inhibitors (2) RoR gamma reverse agonists (3) EZH2 inhibitors (4) NAMPT inhibitors and (5) Several immune check point peptide inhibitor programs.

For more information:  http://aurigene.com/

About Pierre Fabre:

Pierre Fabre is a privately-owned health care company created in 1961 by Mr Pierre Fabre. It is the second largest French independent pharmaceutical group with 2013 sales amounting to about €2 billion (yet to be audited) across 140 countries. The company is structured around two divisions: Pharmaceuticals (Prescription drugs, OTC, Oral care) and Dermo-cosmetics. Prescription drugs are organized around four main franchises: oncology, dermatology, women’s health and neuropsychiatry. Pierre Fabre employs some 10 000 people worldwide, including 1 300 in R&D. The company allocates about 20% of its pharmaceuticals sales to R&D and relies on more than 25 years of experience in the discovery, development and global commercialization of innovative drugs in oncology. Pierre Fabre has a long commitment to oncology and immunology with major R&D centers in France: the Pierre Fabre immunology Centre (CIPF) in Saint Julien en Genevois and the Pierre Fabre Research Institute (IRPF) located on the Toulouse-Oncopole campus  which has been officially recognized as a National Center of Excellence for cancer research since 2012.

 

REFERENCES

http://www.differding.com/data/AUNP_12_A_novel_peptide_therapeutic_targeting_PD_1_immune_checkpoint_pathway_for_cancer_immunotherapy.pdf

http://slideplayer.com/slide/5760496/

P. Sasikumar, R. Shrimali, S. Adurthi, R. Ramachandra, L. Satyam, A. Dhudashiya, D. Samiulla, K. B. Sunilkumar and M. Ramachandra, “A novel peptide therapeutic targeting PD1 immune checkpoint with equipotent antagonism of both ligands and a potential for better management of immune-related adverse events,” Journal for ImmunoTherapy of Cancer, vol. 1, no. Suppl 1,  O24, 2013.

P. G. N. Sasikumar, M. Ramachandra, S. K. Vadlamani, K. R. Vemula, L. K. Satyam, K. Subbarao, K. R. Shrimali and S. Kandepudu (Aurigene Discovery Technologies Ltd, Bangalore, India), “Immunosuppression modulating compounds”, US Patent application US 2011/0318373, 29 Dec 2011.

P. G. Sasikumar, L. K. Satyam, R. K. Shrimali, K. Subbarao, R. Ramachandra, S. Vadlamani, A. Reddy, A. Kumar, A. Srinivas, S. Reddy, S. Gopinath, D. S. Samiulla and M. Ramachandra, “Demonstration of anti-tumor efficacy in multiple preclinical cancer models using a novel peptide inhibitor (Aurigene-012) of the PD1 signaling pathway,” Cancer Research, vol. 72, no. 8 Suppl. 1, Abstract 2850, 2012.

P. G. N. Sasikumar, M. Ramachandra, S. K. Vadlamani, K. R. Shrimali and K. Subbarao, “Therapeutic compounds for immunomodulation” (Aurigene Discovery Technologies Ltd, Bangalore, India), PCT Patent Application WO 2012/168944, 13 Dec 2012.

P. G. N. Sasikumar and M. Ramachandra, “Immunomodulating cyclic compounds from the BC loop of human PD1” (Aurigene Discovery Technologies Ltd, Bangalore, India), PCT Patent Application WO/2013/144704, 3 Oct 2013.

P. G. N. Sasikumar, M. Ramachandra and S. S. S. Naremaddepalli, “Peptidomimetic compounds as immunomodulators” (Aurigene Discovery Technologies Ltd, Bangalore, India), US Patent Application US 2013/0237580, 12 Sep 2013.

A. H. Sharpe, M. J. Butte and S. Oyama (Harvard College), “Modulators of immunoinhibitory receptor PD-1, and methods of use thereof”, PCT Patent Application WO/2011/082400, 7 Jul 2011.

M. Cordingley, “Battle of PD-1 blockade is on”, February 7, 2014 : http://discoveryview.ca/battle-of-pd-1-blockade-is-on/ [Accessed 25 February 2014].

Mr. CSN Murthy

Chief Executive Officer, Aurigene Discovery Technologies Ltd.

Mr. CSN Murthy began his career with ICICI Ventures, India’s first Venture Capital fund. He was subsequently a management consultant to the Pharma and Chemical sectors. Later, he worked in the Business Development and General Management functions in Pharmaceutical companies, including as the Chief Operating Officer of Gland Pharma Ltd. CSN holds a Bachelors degree in Chemical Engineering from the Indian Institute of Technology (IIT), Madras and an MBA from the Indian Institute of Management (IIM), Bangalore.


Dr.Thomas Antony

Associate Research Director, Aurigene Discovery Technologies Ltd.

Dr.Thomas Antony did his Ph.D in Biophysical Chemistry from University of Delhi and had his postdoctoral training at Jawaharlal Nehru University- Delhi, The University of Medicine and Dentistry of New Jersey- USA, and Max Planck Institute for Biophysical Chemistry- Germany. He is the recipient of many research fellowships, including Max Planck Fellowship and Humboldt Research Fellowship.  He has more than 20 years of research experience. Dr.Thomas has published 24 research papers and he is the co-author of three international patents. His core area of expertise is in assay development and screening. At Aurigene, Dr.Thomas leads the Biochemistry and Structural Biology Divisions.  He was the coordinator of Aurigene-University of Malaya collaboration programs.


Dr. Kavitha Nellore

Associate Research Director, Aurigene Discovery Technologies Ltd.

Dr. Kavitha Nellore obtained her PhD in Bioengineering from Pennsylvania State University, USA.  During this time, she was a fellow of the Huck’s Institute of Life Sciences specializing in Biomolecular Transport Dynamics. She has been at Aurigene for more than a decade, and is currently leading a group of cell biologists at both Bangalore and Kuala Lumpur. At Aurigene, she leads multiple drug discovery programs in the therapeutic areas of inflammation, oncology and immuno-oncology. She plays a key role in target selection as well as validation efforts to add to Aurigene’s pipeline. Kavitha also played a key role in coordinating the Aurigene-University of Malaya collaboration.

 

/////////AUNP-12,  Aurigene,  Pierre Fabre Pharmaceuticals, Licensing Agreement,  New Cancer Therapeutic,  Immuno-oncology, AUNP 12, Immune Checkpoint Modulator Targeting the PD-1 Pathway, PEPTIDES

FEW MORE ACADEMIC COMPDS FROM PATENT, REDER DISCRETION NEEDED

C142 H225 N39 O49

L-​Glutamic acid, N2,​N6- ​bis(L-​seryl-​L-​asparaginyl-​L-​threonyl-​L-​seryl-​L-​α-​glutamyl-​L- ​seryl-​L-​phenylalanyl)​-​L-​lysyl-​L-​phenylalanyl-​L-​arginyl-​L-​ valyl-​L-​threonyl-​L-​glutaminyl-​L-​leucyl-​L-​alanyl-​L-​prolyl-​L-​ lysyl-​L-​alanyl-​L-​glutaminyl-​L-​isoleucyl-​L-​lysyl-

3262.54, Sequence Length: 29, 22, 7

multichain; modified (modifications unspecified)

SNTSESFK FRVTQ LAPKAQIKE,  1353564-66-5

SNTSESF

C142 H225 N39 O49

L-​Glutamic acid, N2,​N6– ​bis(L-​seryl-​L-​asparaginyl-​L-​threonyl-​L-​seryl-​L-​α-​glutamyl-​L- ​seryl-​L-​phenylalanyl)​-​L-​lysyl-​L-​phenylalanyl-​L-​arginyl-​L-​ valyl-​L-​threonyl-​L-​glutaminyl-​L-​leucyl-​L-​alanyl-​L-​prolyl-​L-​ lysyl-​L-​alanyl-​L-​glutaminyl-​L-​isoleucyl-​L-​lysyl-

3262.54

NEXT……………………

SNTSESFK FRVTQ LAPKAQI KE

SNTSESF

CAS  1353564-64-3

C142 H226 N40 O48

L-​α-​Glutamine, L-​seryl-​D-​asparaginyl-​L-​threonyl-​L-​seryl-​L-​α-​glutamyl-​L-​seryl-​L-​phenylalanyl-​N6- ​(L-​seryl-​L-​asparaginyl-​L-​threonyl-​L-​seryl-​L-​α-​glutamyl-​L-​ seryl-​L-​phenylalanyl)​-​L-​lysyl-​L-​phenylalanyl-​L-​arginyl-​L-​ valyl-​L-​threonyl-​L-​glutaminyl-​L-​leucyl-​L-​alanyl-​L-​prolyl-​L-​ lysyl-​L-​alanyl-​L-​glutaminyl-​L-​isoleucyl-​L-​lysyl-

MW 3261.55, Sequence Length: 29, 22, 7

multichain; modified

smiles

O=C(N[C@@H](CCCCNC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CO)[C@@H](C)O)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(N)=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](CC(N)=O)NC(=O)[C@@H](N)CO)[C@@H](C)O
NEXT……………..

CAS  1353564-60-9

C142 H226 N40 O48

L-​α-​Glutamine, D-​seryl-​L-​asparaginyl-​L-​threonyl-​L-​seryl-​L-​α-​glutamyl-​L-​seryl-​L-​phenylalanyl-​N6- ​(L-​seryl-​L-​asparaginyl-​L-​threonyl-​L-​seryl-​L-​α-​glutamyl-​L-​ seryl-​L-​phenylalanyl)​-​L-​lysyl-​L-​phenylalanyl-​L-​arginyl-​L-​ valyl-​L-​threonyl-​L-​glutaminyl-​L-​leucyl-​L-​alanyl-​L-​prolyl-​L-​ lysyl-​L-​alanyl-​L-​glutaminyl-​L-​isoleucyl-​L-​lysyl-

3261.55

Sequence Length: 29, 22, 7multichain; modified

SNTSESFKFR VTQLAPKAQI KE

NEXT…………………….

. CAS  1353564-61-0

C142 H226 N40 O48

L-​α-​Glutamine, N2,​N6- ​bis(D-​seryl-​L-​asparaginyl-​L-​threonyl-​L-​seryl-​L-​α-​glutamyl-​L- ​seryl-​L-​phenylalanyl)​-​L-​lysyl-​L-​phenylalanyl-​L-​arginyl-​L-​ valyl-​L-​threonyl-​L-​glutaminyl-​L-​leucyl-​L-​alanyl-​L-​prolyl-​L-​ lysyl-​L-​alanyl-​L-​glutaminyl-​L-​isoleucyl-​L-​lysyl-

3261.55

Sequence Length: 29, 22, 7multichain; modified

SNTSESFK FRVTQ LAPKAQI KE
SNTSESF

/////////////

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