Glucagon like peptide-1 (GLP-1) analogue

ID: ALA4524066

Chembl Id: CHEMBL4524066

PubChem CID: 155543961

Max Phase: Preclinical

Molecular Formula: C172H267N43O51

Molecular Weight: 3753.28

Molecule Type: Protein

Names and Identifiers

Canonical SMILES:  CCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(O)NCCCC[C@H](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)Cc1c[nH]cn1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](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](CCCN=C(N)N)C(=O)NCC(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(=O)O)C(C)C)[C@@H](C)CC)C(=O)O

Standard InChI:  InChI=1S/C172H267N43O51/c1-18-20-21-22-23-24-25-26-27-28-29-30-37-53-129(224)195-116(170(265)266)59-64-128(223)180-68-41-40-50-111(153(248)199-115(62-67-135(232)233)154(249)204-120(73-100-44-33-31-34-45-100)159(254)214-140(93(11)19-2)167(262)192-97(15)146(241)201-122(76-103-79-183-108-49-39-38-48-106(103)108)157(252)203-118(72-90(5)6)158(253)212-138(91(7)8)165(260)200-110(52-43-70-182-172(177)178)149(244)184-81-130(225)193-109(51-42-69-181-171(175)176)148(243)187-84-137(236)237)196-144(239)95(13)189-143(238)94(12)191-152(247)114(58-63-127(174)222)194-131(226)82-185-151(246)113(61-66-134(230)231)198-155(250)117(71-89(3)4)202-156(251)119(75-102-54-56-105(221)57-55-102)205-162(257)124(85-216)208-164(259)126(87-218)209-166(261)139(92(9)10)213-161(256)123(78-136(234)235)206-163(258)125(86-217)210-169(264)142(99(17)220)215-160(255)121(74-101-46-35-32-36-47-101)207-168(263)141(98(16)219)211-132(227)83-186-150(245)112(60-65-133(228)229)197-145(240)96(14)190-147(242)107(173)77-104-80-179-88-188-104/h31-36,38-39,44-49,54-57,79-80,88-99,107,109-126,128,138-142,180,183,216-221,223H,18-30,37,40-43,50-53,58-78,81-87,173H2,1-17H3,(H2,174,222)(H,179,188)(H,184,244)(H,185,246)(H,186,245)(H,187,243)(H,189,238)(H,190,242)(H,191,247)(H,192,262)(H,193,225)(H,194,226)(H,195,224)(H,196,239)(H,197,240)(H,198,250)(H,199,248)(H,200,260)(H,201,241)(H,202,251)(H,203,252)(H,204,249)(H,205,257)(H,206,258)(H,207,263)(H,208,259)(H,209,261)(H,210,264)(H,211,227)(H,212,253)(H,213,256)(H,214,254)(H,215,255)(H,228,229)(H,230,231)(H,232,233)(H,234,235)(H,236,237)(H,265,266)(H4,175,176,181)(H4,177,178,182)/t93-,94-,95-,96-,97-,98+,99+,107-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,128?,138-,139-,140-,141-,142-/m0/s1

Standard InChI Key:  VXEVKSKAINMPFG-QWUNSSNDSA-N

Alternative Forms

1. Parent:

   

   ALA4524066

   LIRAGLUTIDE

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: 3753.28

Molecular Weight (Monoisotopic): 3750.9621

AlogP: ┄

#Rotatable Bonds: ┄

Polar Surface Area: ┄

Molecular Species: ┄

HBA: ┄

HBD: ┄

#RO5 Violations: ┄

HBA (Lipinski): ┄

HBD (Lipinski): ┄

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: ┄

CX LogP: ┄

CX LogD: ┄

Aromatic Rings: ┄

Heavy Atoms: ┄

QED Weighted: ┄

Np Likeness Score: ┄

References

1. Knudsen LB, Nielsen PF, Huusfeldt PO, Johansen NL, Madsen K, Pedersen FZ, Thøgersen H, Wilken M, Agersø H..  (2000)  Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration.,  43  (9): [PMID:10794683] [10.1021/jm9909645]

2. 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]

3. 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]

4. Evers A, Bossart M, Pfeiffer-Marek S, Elvert R, Schreuder H, Kurz M, Stengelin S, Lorenz M, Herling A, Konkar A, Lukasczyk U, Pfenninger A, Lorenz K, Haack T, Kadereit D, Wagner M..  (2018)  Dual Glucagon-like Peptide 1 (GLP-1)/Glucagon Receptor Agonists Specifically Optimized for Multidose Formulations.,  61  (13): [PMID:29879354] [10.1021/acs.jmedchem.8b00292]

5. Li Z, Liu C, Xu X, Qiu Q, Su X, Dai Y, Yang J, Li H, Shi W, Liao C, Pan M, Huang W, Qian H..  (2017)  Discovery of phenylsulfonyl acetic acid derivatives with improved efficacy and safety as potent free fatty acid receptor 1 agonists for the treatment of type 2 diabetes.,  138  [PMID:28689096] [10.1016/j.ejmech.2017.07.001]

6. Cai X, Sun L, Dai Y, Avraham Y, Liu C, Han J, Liu Y, Feng D, Huang W, Qian H..  (2018)  Novel fatty acid chain modified GLP-1 derivatives with prolonged in vivo glucose-lowering ability and balanced glucoregulatory activity.,  26  (9): [PMID:29673717] [10.1016/j.bmc.2018.04.022]

7. Han J, Fu J, Sun L, Han Y, Mao Q, Liao F, Zheng X, Zhu K..  (2018)  Synthesis and pharmaceutical characterization of site specific mycophenolic acid-modified Xenopus glucagon-like peptide-1 analogs.,  9  (1): [PMID:30108901] [10.1039/C7MD00471K]

8. Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek.  (2020)  Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection,  [10.21203/rs.3.rs-23951/v1]

Source

Source(2):

• Scientific Literature
• SARS-CoV-2 Screening Data 2020-21