Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTVIMDE)

DTT Name Glucagon-like peptide 1 receptor (GLP1R)
Synonyms GLP-1R; GLP-1-R; GLP-1 receptor
Gene Name GLP1R
DTT Type
Successful target
 [1]
BioChemical Class
GPCR secretin
UniProt ID
GLP1R_HUMAN
TTD ID
T36075
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAGAPGPLRLALLLLGMVGRAGPRPQGATVSLWETVQKWREYRRQCQRSLTEDPPPATDL
FCNRTFDEYACWPDGEPGSFVNVSCPWYLPWASSVPQGHVYRFCTAEGLWLQKDNSSLPW
RDLSECEESKRGERSSPEEQLLFLYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIH
LNLFASFILRALSVFIKDAALKWMYSTAAQQHQWDGLLSYQDSLSCRLVFLLMQYCVAAN
YYWLLVEGVYLYTLLAFSVLSEQWIFRLYVSIGWGVPLLFVVPWGIVKYLYEDEGCWTRN
SNMNYWLIIRLPILFAIGVNFLIFVRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLL
GTHEVIFAFVMDEHARGTLRFIKLFTELSFTSFQGLMVAILYCFVNNEVQLEFRKSWERW
RLEHLHIQRDSSMKPLKCPTSSLSSGATAGSSMYTATCQASCS
Function
Ligand binding triggers activation of a signaling cascade that leads to the activation of adenylyl cyclase and increased intracellular cAMP levels. Plays a role in regulating insulin secretion in response to GLP-1. G-protein coupled receptor for glucagon-like peptide 1 (GLP-1).
KEGG Pathway
cAMP signaling pathway (hsa04024 )
Neuroactive ligand-receptor interaction (hsa04080 )
Insulin secretion (hsa04911 )
Reactome Pathway
G alpha (s) signalling events (R-HSA-418555 )
Glucagon-type ligand receptors (R-HSA-420092 )
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion (R-HSA-381676 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
8 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Albiglutide DM1JEGF Type-2 diabetes 5A11 Approved [2]
Dulaglutide DMYXBV3 Type-2 diabetes 5A11 Approved [3]
Exenatide DMYHBKN Inflammation 1A00-CA43.1 Approved [4]
Liraglutide DM3FXPS Non-insulin dependent diabetes 5A11 Approved [1]
Lixisenatide DM0QJDC Type-2 diabetes 5A11 Approved [2]
Pramlintide DM0EZ9Q Type-1/2 diabetes 5A10-5A11 Approved [1]
Semaglutide DMAGFOD Type-2 diabetes 5A11 Approved [5]
Tirzepatide DMQNMAT Type 2 diabetes 5A11 Approved [6]
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⏷ Show the Full List of 8 Approved Drug(s)
46 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Efpeglenatide DMKA2PI Type-2 diabetes 5A11 Phase 3 [7]
GLP-1 DMR6YH3 Diabetic complication 5A2Y Phase 3 [5]
GMA102 DMQIE7U Obesity 5B81 Phase 3 [8]
GMA105 DM2XSG0 Obesity 5B81 Phase 3 [9]
LATIN T1D DMAJM12 Type-1 diabetes 5A10 Phase 3 [5]
Orforglipron DMC50VB Obesity 5B81 Phase 3 [10]
PB-119 DM98PS6 Type 2 diabetes 5A11 Phase 3 [11]
Retatrutide DM8WU0Q Obesity 5B81 Phase 3 [12]
Taspoglutide DMPYET9 Type-1 diabetes 5A10 Phase 3 [13]
Avexitide DMQCXSG Congenital hyperinsulinism 5A4Y Phase 2 [14]
BI 456906 DM1NMGJ Type 2 diabetes 5A11 Phase 2 [15]
Efinopegdutide DMAN2V2 Non-alcoholic steatohepatitis DB92.1 Phase 2 [16]
GTP-010 DMN6IDO Dyspepsia MD92 Phase 2 [17]
LY-2428757 DMKYMS2 Type-2 diabetes 5A11 Phase 2 [18]
LY2944876 DML6XWR Diabetic complication 5A2Y Phase 2 [19]
LY3437943 DMN37M6 Obesity 5B81 Phase 2 [20]
NLY01 DMI9OMV Alzheimer disease 8A20 Phase 2 [21]
OI338GT DMNEHY1 Type-1 diabetes 5A10 Phase 2 [22]
ORMD-0901 DMRIO6D Type-2 diabetes 5A11 Phase 2 [23]
PB-1023 DMZCI04 Type-2 diabetes 5A11 Phase 2 [24]
PF-06882961 DM7EJ8S Type 2 diabetes 5A11 Phase 2 [25]
PF-07081532 DM9WHMF Obesity 5B81 Phase 2 [26]
RGT-075 DM1OBHA Type 2 diabetes 5A11 Phase 2 [27]
Semorinemab DMA17VD Alzheimer disease 8A20 Phase 2 [28]
TT-401 DMRQ0SA Type-2 diabetes 5A11 Phase 2 [29]
TTP-054 DMBNU1W Type-2 diabetes 5A11 Phase 2 [30]
TTP273 DMZ6RG2 Type-2 diabetes 5A11 Phase 2 [7]
UNI-rE-4 DMOMI97 Type-2 diabetes 5A11 Phase 2 [31]
AZD0186 DM57J20 Type 2 diabetes 5A11 Phase 1 [32]
CM3.1-AC100 DMSJVX3 Diabetic complication 5A2Y Phase 1 [5]
CNTO-3649 DM8L36X Type-2 diabetes 5A11 Phase 1 [33]
CT 868 DMI7XMU Type 2 diabetes 5A11 Phase 1 [34]
CT-388 DMWHBE5 Obesity 5B81 Phase 1 [16]
CVX 096 DMO23R0 Type-2 diabetes 5A11 Phase 1 [35]
DD01 DM0JKZ6 Obesity 5B81 Phase 1 [36]
GZR18 DM4YR7H Type 2 diabetes 5A11 Phase 1 [37]
JNJ-54728518 DMBV3P8 Type-2 diabetes 5A11 Phase 1 [7]
LY3305677 DMJMLLW Type 2 diabetes 5A11 Phase 1 [38]
NN-9926 DM1RBT8 Type-2 diabetes 5A11 Phase 1 [39]
OG987SC DMZK1GW Type-2 diabetes 5A11 Phase 1 [40]
Pemvidutide DMVOG8A Obesity 5B81 Phase 1 [41]
PF-4603629 DMKOE84 Type-2 diabetes 5A11 Phase 1 [31]
SAR425899 DM53IPE Diabetic complication 5A2Y Phase 1 [42]
SAR438335 DM7QO05 Type-2 diabetes 5A11 Phase 1 [7]
ZP2929 DMRVDUM Type-1 diabetes 5A10 Phase 1 [43]
ZYOG1 DMZ6042 Diabetic complication 5A2Y Phase 1 [44]
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⏷ Show the Full List of 46 Clinical Trial Drug(s)
7 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
CJC-1131 DMQD2LS Type-1 diabetes 5A10 Discontinued in Phase 2 [45]
LY-307161 DMIS7DW Type-2 diabetes 5A11 Discontinued in Phase 2 [46]
RG7685 DMPQC18 Type-2 diabetes 5A11 Discontinued in Phase 2 [47]
CM-GLP-1 DMH40I3 Brain injury NA07.Z Discontinued in Phase 1/2 [48]
LY-315902 DMKMIQ6 Type-2 diabetes 5A11 Discontinued in Phase 1 [49]
AZM-134 DMIWC64 Type-2 diabetes 5A11 Terminated [51]
TH-0318 DMSRDGE Diabetic complication 5A2Y Terminated [5]
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⏷ Show the Full List of 7 Discontinued Drug(s)
1 Preclinical Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
CIN-209 DMBK5CQ Obesity 5B81 Preclinical [50]
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32 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
AC-3174 DMNUE4H Non-alcoholic steatohepatitis DB92.1 Investigative [52]
AMPE4L DM64X25 Diabetic complication 5A2Y Investigative [52]
BETP DM4MZQW Discovery agent N.A. Investigative [53]
CAM-2036 DM4FVDS Non-insulin dependent diabetes 5A11 Investigative [5]
CNTO-736 DMZ57O1 Non-insulin dependent diabetes 5A11 Investigative [5]
C[Asp22-Lys26][Gly8]GLP-1(7-37)-NH2 DMISP20 Discovery agent N.A. Investigative [54]
C[Cpa19-Lys26][Gly8]GLP-1(7-37)-NH2 DMYIJT1 Discovery agent N.A. Investigative [54]
C[Glu18-Lys22][Gly8]GLP-1(7-37)-NH2 DMJR5UD Discovery agent N.A. Investigative [54]
C[Glu19-Lys23][Gly8]GLP-1(7-37)-NH2 DM6O4EZ Discovery agent N.A. Investigative [54]
C[Glu21-Lys25][Gly8]GLP-1(7-37)-NH2 DMA3ZRJ Discovery agent N.A. Investigative [54]
C[Glu21-Lys26][Gly8]GLP-1(7-37)-NH2 DMPK74W Discovery agent N.A. Investigative [54]
C[Glu22-Lys26][Gly8]GLP-1(7-37)-NH2 DM8I0CZ Discovery agent N.A. Investigative [54]
C[Glu22-Orn26][Gly8]GLP-1(7-37)-NH2 DMMA9GE Discovery agent N.A. Investigative [54]
C[Glu23-Lys27][Gly8]GLP-1(7-37)-NH2 DMWYN87 Discovery agent N.A. Investigative [54]
C[Glu24-Lys28][Gly8]GLP-1(7-37)-NH2 DMKZXV3 Discovery agent N.A. Investigative [54]
C[Glu26-Lys30][Gly8]GLP-1(7-37)-NH2 DMX2WCZ Discovery agent N.A. Investigative [54]
C[hGlu22-Lys26][Gly8]GLP-1(7-37)-NH2 DMTP5YZ Discovery agent N.A. Investigative [54]
F-18 exendin-4 derivative PET tracers DMHETZN Diabetic complication 5A2Y Investigative [52]
GLP-17-(7-36) derivative DMBH18C Discovery agent N.A. Investigative [55]
Glu20-Lys24][Gly8][GLP-1(7-37)-NH2 DM0HWB1 Discovery agent N.A. Investigative [54]
Glucagon-like peptide-1 analog DMZLRY2 Non-insulin dependent diabetes 5A11 Investigative [5]
GX-G6 DM1RY6Q Diabetic complication 5A2Y Investigative [5]
HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG-NH2 DMQCGRI Discovery agent N.A. Investigative [54]
HAEGTFTSDVSSYLEGQAAKEIFAWLVKGR DMN54LS Discovery agent N.A. Investigative [56]
PGC GLP-1 DM0NBKR Diabetic complication 5A2Y Investigative [5]
SKL-18287 DMXS9V8 Non-insulin dependent diabetes 5A11 Investigative [5]
SX-GLP1 DMT53U6 Non-insulin dependent diabetes 5A11 Investigative [5]
ZP-3022 DMJ16AD Diabetic complication 5A2Y Investigative [5]
[123I] iodobenzoyl 12-Ex4 DMHWNOS Diabetic complication 5A2Y Investigative [52]
[Gly8, aib22]GLP-1(7-37)-NH2 DM9SP2U Discovery agent N.A. Investigative [54]
[Gly8,Glu22]GLP-1(7,37)-NH2 DMO8U3S Discovery agent N.A. Investigative [54]
[Gly8]GLP-1(7-37)-NH2 DM1SOT4 Discovery agent N.A. Investigative [54]
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⏷ Show the Full List of 32 Investigative Drug(s)

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Irritable bowel syndrome DD91.0 Rectal colon tissue 5.36E-01 -0.01 -0.06
Type 2 diabetes 5A11 Liver tissue 1.25E-01 0.17 1.26
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References

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6 Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. J Clin Endocrinol Metab. 2021 Jan 23;106(2):388-396.
7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
8 Clinical pipeline report, company report or official report of Gmax Biopharm.
9 Clinical pipeline report, company report or official report of Gmax Biopharm.
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11 Clinical pipeline report, company report or official report of PegBio
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13 Pharmacokinetic and pharmacodynamic properties of taspoglutide, a once-weekly, human GLP-1 analogue, after single-dose administration in patients with Type 2 diabetes. Diabet Med. 2009 Nov;26(11):1156-64.
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22 Clinical pipeline report, company report or official report of Novo Nordisk A/S.
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26 ClinicalTrials.gov (NCT05579977) A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED, DOSE RANGING, DOSE FINDING, PARALLEL GROUP STUDY TO ASSESS EFFICACY AND SAFETY OF PF-07081532, AND OPEN LABEL ORAL SEMAGLUTIDE, IN ADULTS WITH TYPE 2 DIABETES MELLITUS (T2DM) INADEQUATELY CONTROLLED ON METFORMIN, AND SEPARATELY PF-07081532 COMPARED TO MATCHING PLACEBO IN ADULTS WITH OBESITY BUT WITHOUT T2DM. U.S.National Institutes of Health.
27 Clinical pipeline report, company report or official report of Regor Therapeutics
28 Antibody semorinemab reduces tau pathology in a transgenic mouse model and engages tau in patients with Alzheimer's disease. Sci Transl Med. 2021 May 12;13(593):eabb2639.
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32 Clinical pipeline report, company report or official report of AstraZeneca
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34 Clinical pipeline report, company report or official report of Carmot Therapeutics.
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39 Clinical pipeline report, company report or official report of Addex Pharmaceuticals.
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42 Company report (Sanofi) (drug: LIXisenatide)
43 Company report (Zealandpharma)
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50 Clinical pipeline report, company report or official report of CinFina Pharma
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52 2005 approvals: Safety first. Nature Reviews Drug Discovery 5, 92-93 (February 2006).
53 A potentiator of orthosteric ligand activity at GLP-1R acts via covalent modification. Nat Chem Biol. 2014 Aug;10(8):629-31.
54 Design and synthesis of conformationally constrained glucagon-like peptide-1 derivatives with increased plasma stability and prolonged in vivo acti... J Med Chem. 2008 May 8;51(9):2758-65.
55 Identification of CJC-1131-albumin bioconjugate as a stable and bioactive GLP-1(7-36) analog. Bioorg Med Chem Lett. 2004 Sep 6;14(17):4395-8.
56 Search for alpha-helical propensity in the receptor-bound conformation of glucagon-like peptide-1. Bioorg Med Chem. 2008 Dec 1;16(23):10106-12.