GLP-17-(7-36) derivative

ID: ALA410972

Chembl Id: CHEMBL410972

Max Phase: Preclinical

Molecular Formula: C149H226N40O45

Molecular Weight: 3297.68

Molecule Type: Protein

Names and Identifiers

Canonical SMILES:  CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(N)=O)C(C)C

Standard InChI:  InChI=1S/C149H226N40O45/c1-17-76(10)119(146(232)167-80(14)126(212)175-104(60-86-63-159-91-36-25-24-35-89(86)91)136(222)177-100(56-73(4)5)137(223)186-117(74(6)7)144(230)174-93(37-26-28-52-150)128(214)160-65-110(197)168-92(122(154)208)39-30-54-158-149(155)156)188-138(224)102(57-83-31-20-18-21-32-83)178-133(219)98(47-51-115(204)205)173-132(218)94(38-27-29-53-151)170-124(210)78(12)164-123(209)77(11)166-131(217)97(44-48-109(153)196)169-111(198)66-161-130(216)96(46-50-114(202)203)172-134(220)99(55-72(2)3)176-135(221)101(59-85-40-42-88(195)43-41-85)179-141(227)106(68-190)182-143(229)108(70-192)183-145(231)118(75(8)9)187-140(226)105(62-116(206)207)180-142(228)107(69-191)184-148(234)121(82(16)194)189-139(225)103(58-84-33-22-19-23-34-84)181-147(233)120(81(15)193)185-112(199)67-162-129(215)95(45-49-113(200)201)171-125(211)79(13)165-127(213)90(152)61-87-64-157-71-163-87/h18-25,31-36,40-43,63-64,71-82,90,92-108,117-121,159,190-195H,17,26-30,37-39,44-62,65-70,150-152H2,1-16H3,(H2,153,196)(H2,154,208)(H,157,163)(H,160,214)(H,161,216)(H,162,215)(H,164,209)(H,165,213)(H,166,217)(H,167,232)(H,168,197)(H,169,198)(H,170,210)(H,171,211)(H,172,220)(H,173,218)(H,174,230)(H,175,212)(H,176,221)(H,177,222)(H,178,219)(H,179,227)(H,180,228)(H,181,233)(H,182,229)(H,183,231)(H,184,234)(H,185,199)(H,186,223)(H,187,226)(H,188,224)(H,189,225)(H,200,201)(H,202,203)(H,204,205)(H,206,207)(H4,155,156,158)/t76-,77-,78-,79-,80-,81+,82+,90-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,117-,118-,119-,120-,121-/m0/s1

Standard InChI Key:  DTHNMHAUYICORS-KTKZVXAJSA-N

Alternative Forms

1. Parent:

   

   ALA410972

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Protein

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 3297.68

Molecular Weight (Monoisotopic): 3295.6626

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HBA: ┄

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CX Acidic pKa: ┄

CX Basic pKa: ┄

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References

1. Léger R, Thibaudeau K, Robitaille M, Quraishi O, van Wyk P, Bousquet-Gagnon N, Carette J, Castaigne JP, Bridon DP..  (2004)  Identification of CJC-1131-albumin bioconjugate as a stable and bioactive GLP-1(7-36) analog.,  14  (17): [PMID:15357960] [10.1016/j.bmcl.2004.06.066]

2. Chi Y, Zhang H, Huang W, Zhou J, Zhou Y, Qian H, Ni S..  (2008)  Microwave-assisted solid phase synthesis, PEGylation, and biological activity studies of glucagon-like peptide-1(7-36) amide.,  16  (16): [PMID:18656368] [10.1016/j.bmc.2008.07.019]

3. Meng H, Krishnaji ST, Beinborn M, Kumar K..  (2008)  Influence of selective fluorination on the biological activity and proteolytic stability of glucagon-like peptide-1.,  51  (22): [PMID:18950150] [10.1021/jm8008579]

4. Maezaki H, Banno Y, Miyamoto Y, Moritoh Y, Asakawa T, Kataoka O, Takeuchi K, Suzuki N, Ikedo K, Kosaka T, Sasaki M, Tsubotani S, Tani A, Funami M, Yamamoto Y, Tawada M, Aertgeerts K, Yano J, Oi S..  (2011)  Discovery of potent, selective, and orally bioavailable quinoline-based dipeptidyl peptidase IV inhibitors targeting Lys554.,  19  (15): [PMID:21741847] [10.1016/j.bmc.2011.06.032]

5. Heard KR, Wu W, Li Y, Zhao P, Woznica I, Lai JH, Beinborn M, Sanford DG, Dimare MT, Chiluwal AK, Peters DE, Whicher D, Sudmeier JL, Bachovchin WW..  (2013)  A general method for making peptide therapeutics resistant to serine protease degradation: application to dipeptidyl peptidase IV substrates.,  56  (21): [PMID:24044354] [10.1021/jm400423p]

6. Han J, Sun L, Chu Y, Li Z, Huang D, Zhu X, Qian H, Huang W..  (2013)  Design, synthesis, and biological activity of novel dicoumarol glucagon-like peptide 1 conjugates.,  56  (24): [PMID:24308627] [10.1021/jm4017448]

7.  (2014)  Nitrogen bicyclic compounds as inhibitors for Scyl1 and Grk5, 

8. Manzo G, Scorciapino MA, Srinivasan D, Attoub S, Mangoni ML, Rinaldi AC, Casu M, Flatt PR, Conlon JM..  (2015)  Conformational Analysis of the Host-Defense Peptides Pseudhymenochirin-1Pb and -2Pa and Design of Analogues with Insulin-Releasing Activities and Reduced Toxicities.,  78  (12): [PMID:26606380] [10.1021/acs.jnatprod.5b00843]

9. McLaughlin CM, Lampis S, Mechkarska M, Coquet L, Jouenne T, King JD, Mangoni ML, Lukic ML, Scorciapino MA, Conlon JM..  (2016)  Purification, Conformational Analysis, and Properties of a Family of Tigerinin Peptides from Skin Secretions of the Crowned Bullfrog Hoplobatrachus occipitalis.,  79  (9): [PMID:27560386] [10.1021/acs.jnatprod.6b00494]

10. Bech EM, Martos-Maldonado MC, Wismann P, Sørensen KK, van Witteloostuijn SB, Thygesen MB, Vrang N, Jelsing J, Pedersen SL, Jensen KJ..  (2017)  Peptide Half-Life Extension: Divalent, Small-Molecule Albumin Interactions Direct the Systemic Properties of Glucagon-Like Peptide 1 (GLP-1) Analogues.,  60  (17): [PMID:28771355] [10.1021/acs.jmedchem.7b00787]

11. Evers A, Haack T, Lorenz M, Bossart M, Elvert R, Henkel B, Stengelin S, Kurz M, Glien M, Dudda A, Lorenz K, Kadereit D, Wagner M..  (2017)  Design of Novel Exendin-Based Dual Glucagon-like Peptide 1 (GLP-1)/Glucagon Receptor Agonists.,  60  (10): [PMID:28448133] [10.1021/acs.jmedchem.7b00174]

12. Pennington MW, Czerwinski A, Norton RS..  (2018)  Peptide therapeutics from venom: Current status and potential.,  26  (10): [PMID:28988749] [10.1016/j.bmc.2017.09.029]

13. Tan L, Yan W, McCorvy JD, Cheng J..  (2018)  Biased Ligands of G Protein-Coupled Receptors (GPCRs): Structure-Functional Selectivity Relationships (SFSRs) and Therapeutic Potential.,  61  (22): [PMID:29939744] [10.1021/acs.jmedchem.8b00435]

14. Palani A, Nawrocki AR, Orvieto F, Bianchi E, Mandić E, Pessi A, Huang C, Deng Q, Toussaint N, Walsh E, Reddy V, Ashley E, He H, Mumick S, Hawes B, Marsh D, Erion M, Nargund R, Carrington PE..  (2022)  Discovery of MK-1462: GLP-1 and Glucagon Receptor Dual Agonist for the Treatment of Obesity and Diabetes.,  13  (8.0): [PMID:35978682] [10.1021/acsmedchemlett.2c00217]

15. Wang P, Hill TA, Mitchell J, Fitzsimmons RL, Xu W, Loh Z, Suen JY, Lim J, Iyer A, Fairlie DP..  (2022)  Modifying a Hydroxyl Patch in Glucagon-like Peptide 1 Produces Biased Agonists with Unique Signaling Profiles.,  65  (17.0): [PMID:35984914] [10.1021/acs.jmedchem.2c00653]

16. Yang Q, Zhou F, Tang X, Wang J, Feng H, Jiang W, Jin L, Jiang N, Yuan Y, Han J, Yan Z..  (2022)  Peptide-based long-acting co-agonists of GLP-1 and cholecystokinin 1 receptors as novel anti-diabesity agents.,  233  [PMID:35231829] [10.1016/j.ejmech.2022.114214]

Source

Source(2):

• Scientific Literature
• Patent Bioactivity Data