Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T36075
(Former ID: TTDS00440)
|
|||||
| Target Name |
Glucagon-like peptide 1 receptor (GLP1R)
|
|||||
| Synonyms |
GLP-1R; GLP-1-R; GLP-1 receptor
Click to Show/Hide
|
|||||
| Gene Name |
GLP1R
|
|||||
| Target Type |
Successful target
|
[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Type 2 diabetes mellitus [ICD-11: 5A11] | |||||
| 2 | Type-1/2 diabete [ICD-11: 5A10-5A11] | |||||
| 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).
Click to Show/Hide
|
|||||
| BioChemical Class |
GPCR secretin
|
|||||
| UniProt ID | ||||||
| Sequence |
MAGAPGPLRLALLLLGMVGRAGPRPQGATVSLWETVQKWREYRRQCQRSLTEDPPPATDL
FCNRTFDEYACWPDGEPGSFVNVSCPWYLPWASSVPQGHVYRFCTAEGLWLQKDNSSLPW RDLSECEESKRGERSSPEEQLLFLYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIH LNLFASFILRALSVFIKDAALKWMYSTAAQQHQWDGLLSYQDSLSCRLVFLLMQYCVAAN YYWLLVEGVYLYTLLAFSVLSEQWIFRLYVSIGWGVPLLFVVPWGIVKYLYEDEGCWTRN SNMNYWLIIRLPILFAIGVNFLIFVRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLL GTHEVIFAFVMDEHARGTLRFIKLFTELSFTSFQGLMVAILYCFVNNEVQLEFRKSWERW RLEHLHIQRDSSMKPLKCPTSSLSSGATAGSSMYTATCQASCS Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T75EH8 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 8 Approved Drugs | + | ||||
| 1 | Albiglutide | Drug Info | Approved | Type-2 diabetes | [2], [3] | |
| 2 | Dulaglutide | Drug Info | Approved | Type-2 diabetes | [3], [4] | |
| 3 | Exenatide | Drug Info | Approved | Type-2 diabetes | [1], [5], [6], [7], [8] | |
| 4 | Liraglutide | Drug Info | Approved | Type-2 diabetes | [9], [10], [8] | |
| 5 | Lixisenatide | Drug Info | Approved | Type-2 diabetes | [11], [12], [13], [8] | |
| 6 | Pramlintide | Drug Info | Approved | Type-1/2 diabetes | [14], [5] | |
| 7 | Semaglutide | Drug Info | Approved | Type-2 diabetes | [15] | |
| 8 | Tirzepatide | Drug Info | Approved | Type 2 diabetes | [16] | |
| Clinical Trial Drug(s) | [+] 46 Clinical Trial Drugs | + | ||||
| 1 | Efpeglenatide | Drug Info | Phase 3 | Type-2 diabetes | [17] | |
| 2 | GLP-1 | Drug Info | Phase 3 | Diabetic complication | [18] | |
| 3 | GMA102 | Drug Info | Phase 3 | Type-2 diabetes | [19] | |
| 4 | GMA105 | Drug Info | Phase 3 | Type-2 diabetes | [20] | |
| 5 | LATIN T1D | Drug Info | Phase 3 | Type-1 diabetes | [21] | |
| 6 | Orforglipron | Drug Info | Phase 3 | Obesity | [22] | |
| 7 | PB-119 | Drug Info | Phase 3 | Type 2 diabetes | [23] | |
| 8 | Retatrutide | Drug Info | Phase 3 | Obesity | [24] | |
| 9 | Taspoglutide | Drug Info | Phase 3 | Type-1 diabetes | [25] | |
| 10 | Avexitide | Drug Info | Phase 2 | Hypoglycemia | [26] | |
| 11 | BI 456906 | Drug Info | Phase 2 | Type 2 diabetes | [27] | |
| 12 | Efinopegdutide | Drug Info | Phase 2 | Non-alcoholic steatohepatitis | [28] | |
| 13 | GTP-010 | Drug Info | Phase 2 | Dyspepsia | [29] | |
| 14 | LY-2428757 | Drug Info | Phase 2 | Type-2 diabetes | [30] | |
| 15 | LY2944876 | Drug Info | Phase 2 | Diabetic complication | [31] | |
| 16 | LY3437943 | Drug Info | Phase 2 | Obesity | [32] | |
| 17 | NLY01 | Drug Info | Phase 2 | Parkinson disease | [33] | |
| 18 | OI338GT | Drug Info | Phase 2 | Type-1/2 diabetes | [34] | |
| 19 | ORMD-0901 | Drug Info | Phase 2 | Type-2 diabetes | [35] | |
| 20 | PB-1023 | Drug Info | Phase 2 | Type-2 diabetes | [36], [8] | |
| 21 | PF-06882961 | Drug Info | Phase 2 | Type 2 diabetes | [37] | |
| 22 | PF-07081532 | Drug Info | Phase 2 | Obesity | [38] | |
| 23 | RGT-075 | Drug Info | Phase 2 | Type 2 diabetes | [39] | |
| 24 | Semorinemab | Drug Info | Phase 2 | Alzheimer disease | [40] | |
| 25 | TT-401 | Drug Info | Phase 2 | Type-2 diabetes | [41], [8] | |
| 26 | TTP-054 | Drug Info | Phase 2 | Type-2 diabetes | [42] | |
| 27 | TTP273 | Drug Info | Phase 2 | Type-2 diabetes | [8] | |
| 28 | UNI-rE-4 | Drug Info | Phase 2 | Type-2 diabetes | [5], [6], [7] | |
| 29 | AZD0186 | Drug Info | Phase 1 | Type 2 diabetes | [43] | |
| 30 | CM3.1-AC100 | Drug Info | Phase 1 | Diabetic complication | [44] | |
| 31 | CNTO-3649 | Drug Info | Phase 1 | Type-2 diabetes | [45] | |
| 32 | CT 868 | Drug Info | Phase 1 | Type 2 diabetes | [46] | |
| 33 | CT-388 | Drug Info | Phase 1 | Obesity | [47] | |
| 34 | CVX 096 | Drug Info | Phase 1 | Type-2 diabetes | [48] | |
| 35 | DD01 | Drug Info | Phase 1 | Obesity | [49] | |
| 36 | GZR18 | Drug Info | Phase 1 | Type 2 diabetes | [50] | |
| 37 | JNJ-54728518 | Drug Info | Phase 1 | Type-2 diabetes | [8] | |
| 38 | LY3305677 | Drug Info | Phase 1 | Type 2 diabetes | [51] | |
| 39 | NN-9926 | Drug Info | Phase 1 | Type-2 diabetes | [52] | |
| 40 | OG987SC | Drug Info | Phase 1 | Type-2 diabetes | [53] | |
| 41 | Pemvidutide | Drug Info | Phase 1 | Obesity | [54] | |
| 42 | PF-4603629 | Drug Info | Phase 1 | Type-2 diabetes | [5], [6], [7] | |
| 43 | SAR425899 | Drug Info | Phase 1 | Diabetic complication | [55] | |
| 44 | SAR438335 | Drug Info | Phase 1 | Type-2 diabetes | [8] | |
| 45 | ZP2929 | Drug Info | Phase 1 | Type-1 diabetes | [8] | |
| 46 | ZYOG1 | Drug Info | Phase 1 | Diabetic complication | [56] | |
| Discontinued Drug(s) | [+] 7 Discontinued Drugs | + | ||||
| 1 | CJC-1131 | Drug Info | Discontinued in Phase 2 | Type-1 diabetes | [57] | |
| 2 | LY-307161 | Drug Info | Discontinued in Phase 2 | Type-2 diabetes | [58] | |
| 3 | RG7685 | Drug Info | Discontinued in Phase 2 | Type-2 diabetes | [59] | |
| 4 | CM-GLP-1 | Drug Info | Discontinued in Phase 1/2 | Brain injury | [60] | |
| 5 | LY-315902 | Drug Info | Discontinued in Phase 1 | Type-2 diabetes | [61] | |
| 6 | AZM-134 | Drug Info | Terminated | Type-2 diabetes | [63] | |
| 7 | TH-0318 | Drug Info | Terminated | Diabetic complication | [64] | |
| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | CIN-209 | Drug Info | Preclinical | Obesity | [62] | |
| Mode of Action | [+] 8 Modes of Action | + | ||||
| Modulator | [+] 30 Modulator drugs | + | ||||
| 1 | Albiglutide | Drug Info | [3], [65], [66] | |||
| 2 | Lixisenatide | Drug Info | [65] | |||
| 3 | GLP-1 | Drug Info | [68], [70] | |||
| 4 | LY2944876 | Drug Info | [80] | |||
| 5 | OI338GT | Drug Info | [84] | |||
| 6 | PB-1023 | Drug Info | [86] | |||
| 7 | TT-401 | Drug Info | [89] | |||
| 8 | TTP-054 | Drug Info | [90] | |||
| 9 | UNI-rE-4 | Drug Info | [6], [7] | |||
| 10 | CT 868 | Drug Info | [93] | |||
| 11 | CT-388 | Drug Info | [78] | |||
| 12 | CVX 096 | Drug Info | [94] | |||
| 13 | OG987SC | Drug Info | [99] | |||
| 14 | PF-4603629 | Drug Info | [6], [7] | |||
| 15 | SAR425899 | Drug Info | [101] | |||
| 16 | ZP2929 | Drug Info | [102] | |||
| 17 | CJC-1131 | Drug Info | [103] | |||
| 18 | LY-307161 | Drug Info | [104] | |||
| 19 | RG7685 | Drug Info | [105] | |||
| 20 | CM-GLP-1 | Drug Info | [106] | |||
| 21 | LY-315902 | Drug Info | [107] | |||
| 22 | AZM-134 | Drug Info | [108] | |||
| 23 | TH-0318 | Drug Info | [68] | |||
| 24 | AMPE4L | Drug Info | [5], [6], [7] | |||
| 25 | CNTO-736 | Drug Info | [68] | |||
| 26 | F-18 exendin-4 derivative PET tracers | Drug Info | [5], [6], [7] | |||
| 27 | Glucagon-like peptide-1 analog | Drug Info | [68] | |||
| 28 | PGC GLP-1 | Drug Info | [68] | |||
| 29 | SKL-18287 | Drug Info | [68] | |||
| 30 | [123I] iodobenzoyl 12-Ex4 | Drug Info | [5], [6], [7] | |||
| Agonist | [+] 39 Agonist drugs | + | ||||
| 1 | Dulaglutide | Drug Info | [3] | |||
| 2 | Liraglutide | Drug Info | [1] | |||
| 3 | Pramlintide | Drug Info | [1] | |||
| 4 | Semaglutide | Drug Info | [68] | |||
| 5 | Tirzepatide | Drug Info | [69] | |||
| 6 | Efpeglenatide | Drug Info | [8] | |||
| 7 | LATIN T1D | Drug Info | [68] | |||
| 8 | Orforglipron | Drug Info | [71] | |||
| 9 | Orforglipron | Drug Info | [72] | |||
| 10 | Retatrutide | Drug Info | [74] | |||
| 11 | Taspoglutide | Drug Info | [75] | |||
| 12 | BI 456906 | Drug Info | [77] | |||
| 13 | Efinopegdutide | Drug Info | [78] | |||
| 14 | GTP-010 | Drug Info | [29] | |||
| 15 | LY3437943 | Drug Info | [81] | |||
| 16 | NLY01 | Drug Info | [82] | |||
| 17 | NLY01 | Drug Info | [83] | |||
| 18 | ORMD-0901 | Drug Info | [85] | |||
| 19 | PF-06882961 | Drug Info | [87] | |||
| 20 | PF-07081532 | Drug Info | [38] | |||
| 21 | RGT-075 | Drug Info | [39] | |||
| 22 | Semorinemab | Drug Info | [88] | |||
| 23 | TTP273 | Drug Info | [8] | |||
| 24 | AZD0186 | Drug Info | [91] | |||
| 25 | CM3.1-AC100 | Drug Info | [68] | |||
| 26 | CNTO-3649 | Drug Info | [92] | |||
| 27 | DD01 | Drug Info | [95] | |||
| 28 | GZR18 | Drug Info | [96] | |||
| 29 | JNJ-54728518 | Drug Info | [8] | |||
| 30 | LY3305677 | Drug Info | [97] | |||
| 31 | NN-9926 | Drug Info | [98] | |||
| 32 | Pemvidutide | Drug Info | [100] | |||
| 33 | SAR438335 | Drug Info | [8] | |||
| 34 | ZYOG1 | Drug Info | [56] | |||
| 35 | CIN-209 | Drug Info | [62] | |||
| 36 | AC-3174 | Drug Info | [5], [6], [7] | |||
| 37 | CAM-2036 | Drug Info | [68] | |||
| 38 | SX-GLP1 | Drug Info | [68] | |||
| 39 | ZP-3022 | Drug Info | [68] | |||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | Exenatide | Drug Info | [67] | |||
| Inhibitor | [+] 21 Inhibitor drugs | + | ||||
| 1 | GMA102 | Drug Info | [19] | |||
| 2 | GMA105 | Drug Info | [20] | |||
| 3 | C[Asp22-Lys26][Gly8]GLP-1(7-37)-NH2 | Drug Info | [110] | |||
| 4 | C[Cpa19-Lys26][Gly8]GLP-1(7-37)-NH2 | Drug Info | [110] | |||
| 5 | C[Glu18-Lys22][Gly8]GLP-1(7-37)-NH2 | Drug Info | [110] | |||
| 6 | C[Glu19-Lys23][Gly8]GLP-1(7-37)-NH2 | Drug Info | [110] | |||
| 7 | C[Glu21-Lys25][Gly8]GLP-1(7-37)-NH2 | Drug Info | [110] | |||
| 8 | C[Glu21-Lys26][Gly8]GLP-1(7-37)-NH2 | Drug Info | [110] | |||
| 9 | C[Glu22-Lys26][Gly8]GLP-1(7-37)-NH2 | Drug Info | [110] | |||
| 10 | C[Glu22-Orn26][Gly8]GLP-1(7-37)-NH2 | Drug Info | [110] | |||
| 11 | C[Glu23-Lys27][Gly8]GLP-1(7-37)-NH2 | Drug Info | [110] | |||
| 12 | C[Glu24-Lys28][Gly8]GLP-1(7-37)-NH2 | Drug Info | [110] | |||
| 13 | C[Glu26-Lys30][Gly8]GLP-1(7-37)-NH2 | Drug Info | [110] | |||
| 14 | C[hGlu22-Lys26][Gly8]GLP-1(7-37)-NH2 | Drug Info | [110] | |||
| 15 | GLP-17-(7-36) derivative | Drug Info | [111] | |||
| 16 | Glu20-Lys24][Gly8][GLP-1(7-37)-NH2 | Drug Info | [110] | |||
| 17 | HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG-NH2 | Drug Info | [110] | |||
| 18 | HAEGTFTSDVSSYLEGQAAKEIFAWLVKGR | Drug Info | [112] | |||
| 19 | [Gly8, aib22]GLP-1(7-37)-NH2 | Drug Info | [110] | |||
| 20 | [Gly8,Glu22]GLP-1(7,37)-NH2 | Drug Info | [110] | |||
| 21 | [Gly8]GLP-1(7-37)-NH2 | Drug Info | [110] | |||
| Agonist | [+] 1 Agonist drugs | + | ||||
| 1 | PB-119 | Drug Info | [73] | |||
| Antagonist | [+] 1 Antagonist drugs | + | ||||
| 1 | Avexitide | Drug Info | [76] | |||
| Stimulator | [+] 1 Stimulator drugs | + | ||||
| 1 | LY-2428757 | Drug Info | [79] | |||
| Modulator (allosteric modulator) | [+] 1 Modulator (allosteric modulator) drugs | + | ||||
| 1 | BETP | Drug Info | [109] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: PF-06882961 | Ligand Info | |||||
| Structure Description | Non peptide agonist PF-06882961, bound to Glucagon-Like peptide-1 (GLP-1) Receptor | PDB:6X1A | ||||
| Method | Electron microscopy | Resolution | 2.50 Å | Mutation | No | [87] |
| PDB Sequence |
ATVSLWETVQ
37 KWREYRRQCQ47 RSLTEDPPPA57 TDLFCNRTFD67 EYACWPDGEP77 GSFVNVSCPW 87 YLPWASSVPQ97 GHVYRFCTAE107 GLWLQKDNSS117 LPWRDLSECE127 ESSPEEQLLF 143 LYIIYTVGYA153 LSFSALVIAS163 AILLGFRHLH173 CTRNYIHLNL183 FASFILRALS 193 VFIKDAALKW203 MYSTAAQQHQ213 WDGLLSYQDS223 LSCRLVFLLM233 QYCVAANYYW 243 LLVEGVYLYT253 LLAFSVFSEQ263 WIFRLYVSIG273 WGVPLLFVVP283 WGIVKYLYED 293 EGCWTRNSNM303 NYWLIIRLPI313 LFAIGVNFLI323 FVRVICIVVS333 KLKANLMCKT 343 DIKCRLAKST353 LTLIPLLGTH363 EVIFAFVMDE373 HARGTLRFIK383 LFTELSFTSF 393 QGLMVAILYC403 FVNNEVQLEF413 RKSWERWRLE423
|
|||||
|
|
SER31
3.582
LEU32
3.570
TRP33
3.571
VAL36
3.614
GLN37
3.398
GLU138
4.582
LEU141
3.612
LYS197
3.076
LEU201
3.648
TRP203
3.307
SER206
3.569
THR207
3.696
LEU217
3.883
LEU218
4.002
|
|||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 3-Sulfinoalanine | Ligand Info | |||||
| Structure Description | Structure of the human GLP-1 receptor complex with PF-06372222 | PDB:5VEW | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | Yes | [113] |
| PDB Sequence |
SPEEQLLFLY
145 IIYTVGYALS155 FSALVIASAI165 LLGFRHLHCT175 RNYIHLNLFA185 SFILRALCVF 195 FKDAALKWLS219 YQDSLACRLV229 FLLQYCVAAN240 YYWLLVEGVY250 LYTLLAFNIF 1004 EMLRIDEGLR1014 LKIYKDTEGY1024 YTIGIGHLLT1034 KSPSLNAAKS1044 ELDKAIGRNT 1054 NGVITKDEAE1064 KLFNQDVDAA1074 VRGILRNAKL1084 KPVYDSLDAV1094 RRAALINMVF 1104 QMGETGVAGF1114 TNSLRMLQQK1124 RWDEAAVNLA1134 KSRWYNQTPN1144 RAKRVITTFR 1154 TGTWDAYSEQ263 WIFRLYVAIG273 WGVPLLFVVP283 WGIVKYLYED293 EGCWTRNSNM 303 NYWLIIRLPI313 LFACIVNFLI323 FVRVICIVVS333 KLKANLMCKT343 DIAFRLAKST 353 LTLIPLLCTH363 EVIFAFVMDR380 FIKLFTELSF390 TSFQGLMVAI400 LYCFVNNEVQ 410 LEFRKSWERW420 RL
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
|
|
|
There is no similarity protein (E value < 0.005) for this target
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| cAMP signaling pathway | hsa04024 | Affiliated Target |
|
| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
|
| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Insulin secretion | hsa04911 | Affiliated Target |
|
| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 8.15E-05 |
|---|---|---|---|---|---|
| Closeness centrality | 2.04E-01 | Radiality | 1.36E+01 | Clustering coefficient | 1.67E-01 |
| Neighborhood connectivity | 2.08E+01 | Topological coefficient | 2.77E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | cAMP signaling pathway | |||||
| 2 | Neuroactive ligand-receptor interaction | |||||
| 3 | Insulin secretion | |||||
| Reactome | [+] 3 Reactome Pathways | + | ||||
| 1 | Glucagon-like Peptide-1 (GLP1) regulates insulin secretion | |||||
| 2 | G alpha (s) signalling events | |||||
| 3 | Glucagon-type ligand receptors | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | GPCRs, Class B Secretin-like | |||||
| 2 | Integration of energy metabolism | |||||
| 3 | GPCR ligand binding | |||||
| 4 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7386). | |||||
| REF 3 | 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81. | |||||
| REF 4 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7638). | |||||
| REF 5 | 2005 approvals: Safety first. Nature Reviews Drug Discovery 5, 92-93 (February 2006). | |||||
| REF 6 | Exenatide and liraglutide: different approaches to develop GLP-1 receptor agonists (incretin mimetics)--preclinical and clinical results. Best Pract Res Clin Endocrinol Metab. 2009 Aug;23(4):463-77. | |||||
| REF 7 | Bydureon: first once weekly GLP-1 receptor agonist (exenatide LAR). Rev Med Liege. 2014 Apr;69(4):214-9. | |||||
| REF 8 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 9 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1133). | |||||
| REF 10 | Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5. | |||||
| REF 11 | 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76. | |||||
| REF 12 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7387). | |||||
| REF 13 | ClinicalTrials.gov (NCT02049034) Lixisenatide-The Effects on Glucose and Lipid Metabolism in Type 2 Diabetes. U.S. National Institutes of Health. | |||||
| REF 14 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7482). | |||||
| REF 15 | 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85. | |||||
| REF 16 | FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 215866. | |||||
| REF 17 | ClinicalTrials.gov (NCT03496298) Effect of Efpeglenatide on Cardiovascular Outcomes (AMPLITUDE-O). U.S. National Institutes of Health. | |||||
| REF 18 | Clinical pipeline report, company report or official report of Emisphere Technologies Inc. | |||||
| REF 19 | Clinical pipeline report, company report or official report of Gmax Biopharm. | |||||
| REF 20 | Clinical pipeline report, company report or official report of Gmax Biopharm. | |||||
| REF 21 | Clinical pipeline report, company report or official report of Novo Nordisk A/S. | |||||
| REF 22 | ClinicalTrials.gov (NCT05869903) A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once-Daily Oral LY3502970 Compared With Placebo in Adult Participants With Obesity or Overweight With Weight-Related Comorbidities (ATTAIN-1). U.S.National Institutes of Health. | |||||
| REF 23 | ClinicalTrials.gov (NCT04504396) A Multicenter, Randomized, Double-blinded, Placebo-controlled Trial Comparing the Efficacy and Safety of PB-119 in Combination With Metformin in Subjects With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin Alone. U.S.National Institutes of Health. | |||||
| REF 24 | ClinicalTrials.gov (NCT05882045) A Randomized, Double-Blind, Phase 3 Study to Investigate the Efficacy and Safety of LY3437943 Once Weekly Compared to Placebo in Participants With Severe Obesity and Established Cardiovascular Disease. U.S.National Institutes of Health. | |||||
| REF 25 | ClinicalTrials.gov (NCT01018173) A Study of Taspoglutide in Patients With Inadequately Controlled Diabetes Mellitus Type 2 and Cardiovascular Disease. U.S. National Institutes of Health. | |||||
| REF 26 | ClinicalTrials.gov (NCT03373435) A Phase 2, Multicenter, Randomized, Single-Blind, Placebo-Controlled Cross-over Study to Assess the Efficacy and Safety of Exendin 9-39 in Patients With Postbariatric Hypoglycemia. U.S.National Institutes of Health. | |||||
| REF 27 | ClinicalTrials.gov (NCT04153929) A Study to Test Whether Different Doses of BI 456906 Are Effective in Treating Adults With Type 2 Diabetes.. U.S. National Institutes of Health. | |||||
| REF 28 | ClinicalTrials.gov (NCT04944992) A Phase 2a, Randomized, Active-Comparator-Controlled, Open-Label Study to Evaluate the Efficacy and Safety of Efinopegdutide (MK-6024) in Individuals With Nonalcoholic Fatty Liver Disease. U.S.National Institutes of Health. | |||||
| REF 29 | Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313. | |||||
| REF 30 | ClinicalTrials.gov (NCT00804986) A Study for Patients With Type 2 Diabetes Mellitus. U.S. National Institutes of Health. | |||||
| REF 31 | ClinicalTrials.gov (NCT02119819) A Study to Compare a New Drug for Type 2 Diabetes to Placebo and to a Treatment Already Available for Type 2 Diabetes. U.S. National Institutes of Health. | |||||
| REF 32 | ClinicalTrials.gov (NCT04881760) A Phase 2 Study of Once-Weekly LY3437943 Compared With Placebo in Participants Who Have Obesity or Are Overweight With Weight-Related Comorbidities. U.S.National Institutes of Health. | |||||
| REF 33 | ClinicalTrials.gov (NCT04154072) Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of 36 Weeks of Treatment With NLY01 in Early-stage Parkinson's Disease. U.S.National Institutes of Health. | |||||
| REF 34 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034087) | |||||
| REF 35 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028920) | |||||
| REF 36 | Clinical pipeline report, company report or official report of PhaseBio Pharmaceuticals. | |||||
| REF 37 | ClinicalTrials.gov (NCT03985293) A 16 Week Study to Evaluate the Efficacy and Safety of PF-06882961 in Adults With Type 2 Diabetes Mellitus. U.S. National Institutes of Health. | |||||
| REF 38 | 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. | |||||
| REF 39 | Clinical pipeline report, company report or official report of Regor Therapeutics | |||||
| REF 40 | ClinicalTrials.gov (NCT03828747) A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of MTAU9937A in Patients With Moderate Alzheimer's Disease. U.S.National Institutes of Health. | |||||
| REF 41 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035378) | |||||
| REF 42 | ClinicalTrials.gov (NCT01665352) A Study to Evaluate Safety and Efficacy of TTP054 for 12 Weeks in Subjects With Type 2 Diabetes. U.S. National Institutes of Health. | |||||
| REF 43 | ClinicalTrials.gov (NCT05694741) A Phase 1 Randomized, Single-blind, Placebo-controlled, First-in-Human and Sequential Group Study to Assess Safety, Tolerability, and Pharmacokinetics of AZD0186 Following Single Ascending Doses Via Oral Administration. U.S.National Institutes of Health. | |||||
| REF 44 | ClinicalTrials.gov (NCT01165502) Clinical Study to Investigate Safety and Tolerability and Pharmacokinetics of Multiple Ascending Doses of CM3.1-AC100 in Healthy Male Volunteers. U.S. National Institutes of Health. | |||||
| REF 45 | ClinicalTrials.gov (NCT00882726) A Study of the Safety, Pharmacokinetics, and Pharmacodynamics of CNTO 3649 in Healthy Adults and Patients With Type 2 Diabetes Mellitus. U.S. National Institutes of Health. | |||||
| REF 46 | Clinical pipeline report, company report or official report of Carmot Therapeutics. | |||||
| REF 47 | ClinicalTrials.gov (NCT04838405) A Phase 1 Randomized, Double Blind, Placebo Controlled, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CT-388 in Otherwise Healthy Overweight and Obese Adult Participants and in Obese Patients With Type 2 Diabetes Mellitus. U.S.National Institutes of Health. | |||||
| REF 48 | ClinicalTrials.gov (NCT01301456) Single-Dose And Multiple-Dose Safety And Tolerability Study Of PF-04856883 In Type 2 Diabetic Adult Females. U.S. National Institutes of Health. | |||||
| REF 49 | ClinicalTrials.gov (NCT04812262) A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Dose Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DD01 in Overweight/Obese Subjects With T2DM and NAFLD. U.S.National Institutes of Health. | |||||
| REF 50 | ClinicalTrials.gov (NCT05328726) A Double-blind, Randomized, Placebo-controlled, Sequential, Single, Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Parameters of Subcutaneous Injections of GZR18 in Healthy Subjects. U.S.National Institutes of Health. | |||||
| REF 51 | ClinicalTrials.gov (NCT03928379) A Multiple-Ascending Dose Study in Patients With Type 2 Diabetes Mellitus to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3305677. U.S.National Institutes of Health. | |||||
| REF 52 | ClinicalTrials.gov (NCT01405261) Trial Investigating the Safety of NNC 0113-0987 in Healthy Male Subjects. U.S. National Institutes of Health. | |||||
| REF 53 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800036982) | |||||
| REF 54 | ClinicalTrials.gov (NCT05292911) A 12-Week Extension Study of ALT-801 in Diabetic and Non-Diabetic Overweight and Obese Subjects With Non-alcoholic Fatty Liver Disease (NAFLD). U.S.National Institutes of Health. | |||||
| REF 55 | ClinicalTrials.gov (NCT02411825) Multiple Ascending Dose Study in Healthy Male Subjects. U.S. National Institutes of Health. | |||||
| REF 56 | 2011 Pipeline of Zydus Cadila Group. | |||||
| REF 57 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015896) | |||||
| REF 58 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015327) | |||||
| REF 59 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031660) | |||||
| REF 60 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023519) | |||||
| REF 61 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008960) | |||||
| REF 62 | Clinical pipeline report, company report or official report of CinFina Pharma | |||||
| REF 63 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008696) | |||||
| REF 64 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017892) | |||||
| REF 65 | GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus.Nat Rev Endocrinol.2012 Dec;8(12):728-42. | |||||
| REF 66 | Glucagon-like peptide-1 analogues: An overview.Indian J Endocrinol Metab.2013 May;17(3):413-21. | |||||
| REF 67 | Improved glycemic control and reduction of cardiometabolic risk factors in subjects with type 2 diabetes and metabolic syndrome treated with exenatide in a clinical practice setting. Diabetes TechnolTher. 2009 Jun;11(6):353-9. | |||||
| REF 68 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 249). | |||||
| REF 69 | 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. | |||||
| REF 70 | Influence of selective fluorination on the biological activity and proteolytic stability of glucagon-like peptide-1. J Med Chem. 2008 Nov 27;51(22):7303-7. | |||||
| REF 71 | Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist. Proc Natl Acad Sci U S A. 2020 Nov 24;117(47):29959-29967. | |||||
| REF 72 | Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1b, multicentre, blinded, placebo-controlled, randomized, multiple-ascending-dose study in people with type 2 diabetes. Diabetes Obes Metab. 2023 Sep;25(9):2642-2649. | |||||
| REF 73 | Clinical pipeline report, company report or official report of PegBio | |||||
| REF 74 | Is retatrutide (LY3437943), a GLP-1, GIP, and glucagon receptor agonist a step forward in the treatment of diabetes and obesity? Expert Opin Investig Drugs. 2023 May;32(5):355-359. | |||||
| REF 75 | 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. | |||||
| REF 76 | PREVENT: A Randomized, Placebo-controlled Crossover Trial of Avexitide for Treatment of Postbariatric Hypoglycemia. J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3235-e3248. | |||||
| REF 77 | Clinical pipeline report, company report or official report of Boehringer Ingelheim. | |||||
| REF 78 | Emerging glucagon-like peptide 1 receptor agonists for the treatment of obesity. Expert Opin Emerg Drugs. 2021 Sep;26(3):231-243. | |||||
| REF 79 | Role and development of GLP-1 receptor agonists in the management of diabetes. Diabetes Metab Syndr Obes. 2009; 2: 37-49. | |||||
| REF 80 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 81 | LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metab. 2022 Sep 6;34(9):1234-1247.e9. | |||||
| REF 82 | GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension. Cell Rep. 2020 Nov 3;33(5):108271. | |||||
| REF 83 | Topical and systemic GLP-1R agonist administration both rescue retinal ganglion cells in hypertensive glaucoma. Front Cell Neurosci. 2023 Jun 9;17:1156829. | |||||
| REF 84 | Clinical pipeline report, company report or official report of Novo Nordisk A/S. | |||||
| REF 85 | Novel glucagon-like peptide-1 analog delivered orally reduces postprandial glucose excursions in porcine and canine models. J Diabetes Sci Technol. 2010 Nov 1;4(6):1516-23. | |||||
| REF 86 | On-target Effects of GLP-1 Receptor Agonists on Thyroid C-cells in Rats and Mice. Toxicol Pathol February 2013 vol. 41 no. 2 303-309. | |||||
| REF 87 | Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists. Mol Cell. 2020 Nov 5;80(3):485-500.e7. | |||||
| REF 88 | 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. | |||||
| REF 89 | Relationship between systemic cytokines and complement factor H Y402H polymorphism in patients with dry age-related macular degeneration. Am J Ophthalmol. 2013 Dec;156(6):1176-83. | |||||
| REF 90 | Small Molecule Drug Discovery at the Glucagon-Like Peptide-1 Receptor. Exp Diabetes Res. 2012; 2012: 709893. | |||||
| REF 91 | Clinical pipeline report, company report or official report of AstraZeneca | |||||
| REF 92 | GLP-1 receptor activation inhibits VLDL production and reverses hepatic steatosis by decreasing hepatic lipogenesis in high-fat-fed APOE*3-Leiden mice. PLoS One. 2012;7(11):e49152. | |||||
| REF 93 | Clinical pipeline report, company report or official report of Carmot Therapeutics. | |||||
| REF 94 | Chemically programmed antibodies. Trends Biotechnol. 2014 April; 32(4): 186-197. | |||||
| REF 95 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2023. Adis Insight | |||||
| REF 96 | GZR18, a novel long-acting GLP-1 analog, demonstrated positive in vitro and in vivo pharmacokinetic and pharmacodynamic characteristics in animal models. Eur J Pharmacol. 2022 Aug 5;928:175107. | |||||
| REF 97 | IBI362?(LY3305677), a weekly-dose GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple ascending dose phase 1b study. EClinicalMedicine. 2021 Aug 13;39:101088. | |||||
| REF 98 | Clinical pipeline report, company report or official report of Addex Pharmaceuticals. | |||||
| REF 99 | Clinical pipeline report, company report or official report of Novo Nordisk A/S. | |||||
| REF 100 | Effects of ALT-801, a GLP-1 and glucagon receptor dual agonist, in a translational mouse model of non-alcoholic steatohepatitis. Sci Rep. 2022 Apr 23;12(1):6666. | |||||
| REF 101 | Company report (Sanofi) (drug: LIXisenatide) | |||||
| REF 102 | Company report (Zealandpharma) | |||||
| REF 103 | Pharmacokinetics and tolerability of a novel long-acting glucagon-like peptide-1 analog, CJC-1131, in healthy and diabetic subjects. Int J Clin Pharmacol Ther. 2008 Sep;46(9):443-52. | |||||
| REF 104 | Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Sep;25(7):565-97. | |||||
| REF 105 | Company report (Roche pipeline: October 16, 2012) | |||||
| REF 106 | Reversal of diabetes in rats using GLP-1-expressing adult pancreatic duct-like precursor cells transformed from acinar to ductal cells. Stem Cells Dev. 2009 Sep;18(7):991-1002. | |||||
| REF 107 | Glucagon-like peptide-1 analogue LY315902: effect on intestinal motility and release of insulin and somatostatin. Regul Pept. 2002 Jun 15;106(1-3):89-95. | |||||
| REF 108 | US patent application no. 2011,0171,312, Modified therapeutic peptides, methods of their preparation and use. | |||||
| REF 109 | A potentiator of orthosteric ligand activity at GLP-1R acts via covalent modification. Nat Chem Biol. 2014 Aug;10(8):629-31. | |||||
| REF 110 | 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. | |||||
| REF 111 | 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. | |||||
| REF 112 | 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. | |||||
| REF 113 | Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators. Nature. 2017 Jun 8;546(7657):312-315. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.