Peptide Information

General Information of This Peptide
Peptide ID
PEP00176
Peptide Name
GLP-1 analogue
Structure
Sequence
H-Aib-EGTFTSDVSSYLEEQAAKEFIAWLVKGGPSSGAPPPSC
Peptide Type
Linear
Receptor Name
Glutamate receptor ionotropic, NMDA 1 (GRIN1)
  Receptor Info 
PDC Transmembrane Types Cell targeting peptides (CTPs)
Formula
C184H274N46O61S
Isosmiles
[H]NCCCC[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)N[H])NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O[H])cc1)NC(=O)[C@H](CO[H])NC(=O)[C@H](CO[H])NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO[H])NC(=O)[C@@]([H])(NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@]([H])(NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](Cc1cn([H])cn1)N[H])[C@@H](C)O[H])[C@@H](C)O[H])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](Cc1cn([H])c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCCN[H])C(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CO[H])C(=O)N[C@@H](CO[H])C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO[H])C(=O)N[C@@H](CS[H])C(=O)O)C(C)C)[C@@H](C)CC
InChI
InChI=1S/C184H274N46O61S/c1-17-93(10)147(178(284)200-96(13)152(258)208-121(71-103-74-190-108-39-25-24-38-106(103)108)164(270)210-117(67-90(4)5)165(271)223-145(91(6)7)176(282)207-109(40-26-28-60-185)154(260)193-76-135(241)191-80-139(245)227-62-30-42-130(227)174(280)217-125(83-233)171(277)215-123(81-231)156(262)195-77-136(242)197-97(14)181(287)229-64-32-44-132(229)183(289)230-65-33-45-133(230)182(288)228-63-31-43-131(228)175(281)218-126(84-234)173(279)221-129(87-292)184(290)291)225-166(272)119(68-100-34-20-18-21-35-100)211-161(267)115(54-59-143(252)253)204-158(264)110(41-27-29-61-186)202-151(257)95(12)198-150(256)94(11)199-157(263)112(50-55-134(188)240)203-159(265)113(52-57-141(248)249)205-160(266)114(53-58-142(250)251)206-162(268)116(66-89(2)3)209-163(269)118(70-102-46-48-105(239)49-47-102)212-169(275)124(82-232)216-172(278)128(86-236)219-177(283)146(92(8)9)224-168(274)122(73-144(254)255)213-170(276)127(85-235)220-180(286)149(99(16)238)226-167(273)120(69-101-36-22-19-23-37-101)214-179(285)148(98(15)237)222-138(244)79-194-155(261)111(51-56-140(246)247)201-137(243)78-192-153(259)107(187)72-104-75-189-88-196-104/h18-25,34-39,46-49,74-75,88-99,107,109-133,145-149,190,231-239,292H,17,26-33,40-45,50-73,76-87,185-187H2,1-16H3,(H2,188,240)(H,189,196)(H,191,241)(H,192,259)(H,193,260)(H,194,261)(H,195,262)(H,197,242)(H,198,256)(H,199,263)(H,200,284)(H,201,243)(H,202,257)(H,203,265)(H,204,264)(H,205,266)(H,206,268)(H,207,282)(H,208,258)(H,209,269)(H,210,270)(H,211,267)(H,212,275)(H,213,276)(H,214,285)(H,215,277)(H,216,278)(H,217,280)(H,218,281)(H,219,283)(H,220,286)(H,221,279)(H,222,244)(H,223,271)(H,224,274)(H,225,272)(H,226,273)(H,246,247)(H,248,249)(H,250,251)(H,252,253)(H,254,255)(H,290,291)/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-,127-,128-,129-,130-,131-,132-,133-,145-,146-,147-,148-,149-/m0/s1
InChIKey
OSHIGSJCNKZRNG-IQGNDCGWSA-N
Pharmaceutical Properties
Molecule Weight
4138.544
Polar area
1671.23
Complexity
4135.947326
xlogp Value
-19.7567
Heavy Count
292
Rot Bonds
140
Hbond acc
60
Hbond Donor
57
Each Peptide-drug Conjugate Related to This Peptide
Full Information of The Activity Data of The PDC(s) Related to This Peptide
GLP-1-MK-801 [Preclinical]
 PDC Info 
Obtained from the Model Organism Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Obesity
Efficacy Data Vehicle-corrected weight loss rate
9.50%
Administration Time 1 dose
Administration Dosage 0.22 nmol
Evaluation Method This study revealed a superior vehicle-corrected weight loss of 9.5% in response to the GLP-1-MK-801 infusion relative to a weight loss of 4.5% after semaglutide infusion (Fig. 4b).
MOA of PDC
Treatment with GLP-1-inactive MK-801 produced no additional weight loss efficacy relative to GLP-1 monotherapy (Fig. 2g-i), indicating that the pronounced weight loss induced by GLP-1-MK-801 is driven by concerted and site-directed pharmacological GLP-1 receptor agonism and NMDA receptor antagonism.
In Vivo Model High-fat high-sucrose-fed mice
Half life period 1.9 h
Experiment 2 Reporting the Activity Data of This PDC [1]
Indication Obesity
Efficacy Data Vehicle-corrected weight loss rate
15.20%
Administration Time Once a day for 9 days
Administration Dosage 100 nmol kg-1
Evaluation Method We observed a pronounced vehicle-corrected weight loss of 15.2% in the group treated with GLP-1-MK-801 compared with 3.5% in the group treated with the parent GLP-1 analogue after 9days of treatment, underscoring that the weight-lowering efficacy of the conjugate is intact in the absence of functional MC4R signalling (Fig. 3l,m).
MOA of PDC
Treatment with GLP-1-inactive MK-801 produced no additional weight loss efficacy relative to GLP-1 monotherapy (Fig. 2g-i), indicating that the pronounced weight loss induced by GLP-1-MK-801 is driven by concerted and site-directed pharmacological GLP-1 receptor agonism and NMDA receptor antagonism.
In Vivo Model Mc4r-KO mice
Half life period 1.9 h
Experiment 3 Reporting the Activity Data of This PDC [1]
Indication Obesity
Efficacy Data Vehicle-corrected weight loss rate
23.20%
Administration Time Once a day for 14 days
Administration Dosage 100 nmol kg-1
Evaluation Method Over a 14-day treatment period, GLP-1-MK-801 synergistically lowered body weight compared with the dose-matched monotherapies and produced a vehicle-corrected weight loss of 23.2%.
MOA of PDC
Treatment with GLP-1-inactive MK-801 produced no additional weight loss efficacy relative to GLP-1 monotherapy (Fig. 2g-i), indicating that the pronounced weight loss induced by GLP-1-MK-801 is driven by concerted and site-directed pharmacological GLP-1 receptor agonism and NMDA receptor antagonism.
In Vivo Model DIO mice
Half life period 1.9 h
Experiment 4 Reporting the Activity Data of This PDC [1]
Indication Obesity
Efficacy Data Lean mass rate
8%
Administration Time Once a day for 14 days
Administration Dosage 100 nmol kg-1
Evaluation Method GLP-1-MK-801 produced a vehicle-corrected reduction in body fat mass of 45%, accompanied by an 8% loss in lean mass.
MOA of PDC
Treatment with GLP-1-inactive MK-801 produced no additional weight loss efficacy relative to GLP-1 monotherapy (Fig. 2g-i), indicating that the pronounced weight loss induced by GLP-1-MK-801 is driven by concerted and site-directed pharmacological GLP-1 receptor agonism and NMDA receptor antagonism.
In Vivo Model DIO mice
Half life period 1.9 h
Experiment 5 Reporting the Activity Data of This PDC [1]
Indication Obesity
Efficacy Data Fat mass reduction rate
45%
Administration Time Once a day for 14 days
Administration Dosage 100 nmol kg-1
Evaluation Method GLP-1-MK-801 produced a vehicle-corrected reduction in body fat mass of 45%, accompanied by an 8% loss in lean mass.
MOA of PDC
Treatment with GLP-1-inactive MK-801 produced no additional weight loss efficacy relative to GLP-1 monotherapy (Fig. 2g-i), indicating that the pronounced weight loss induced by GLP-1-MK-801 is driven by concerted and site-directed pharmacological GLP-1 receptor agonism and NMDA receptor antagonism.
In Vivo Model DIO mice
Half life period 1.9 h
References
Ref 1 GLP-1-directed NMDA receptor antagonism for obesity treatment. Nature. 2024 May;629(8014):1133-1141. doi: 10.1038/s41586-024-07419-8. Epub 2024 May 15.