Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T30834
(Former ID: TTDI01947)
|
|||||
| Target Name |
Amylin receptor (IAPPR)
|
|||||
| Synonyms |
Complex of Calcitonin receptor and Receptor activity-modifying protein
Click to Show/Hide
|
|||||
| Gene Name |
CALCR-RAMP1/RAMP2/RAMP3
|
|||||
| Target Type |
Clinical trial target
|
[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Type 2 diabetes mellitus [ICD-11: 5A11] | |||||
| Function |
Transports the calcitonin gene-related peptide type 1 receptor (CALCRL) to the plasma membrane. Acts as a receptor for calcitonin-gene-related peptide (CGRP) together with CALCRL.
Click to Show/Hide
|
|||||
| UniProt ID | ||||||
| Sequence |
MRFTFTSRCLALFLLLNHPTPILPAFSNQTYPTIEPKPFLYVVGRKKMMDAQYKCYDRMQ
QLPAYQGEGPYCNRTWDGWLCWDDTPAGVLSYQFCPDYFPDFDPSEKVTKYCDEKGVWFK HPENNRTWSNYTMCNAFTPEKLKNAYVLYYLAIVGHSLSIFTLVISLGIFVFFRSLGCQR VTLHKNMFLTYILNSMIIIIHLVEVVPNGELVRRDPVSCKILHFFHQYMMACNYFWMLCE GIYLHTLIVVAVFTEKQRLRWYYLLGWGFPLVPTTIHAITRAVYFNDNCWLSVETHLLYI IHGPVMAALVVNFFFLLNIVRVLVTKMRETHEAESHMYLKAVKATMILVPLLGIQFVVFP WRPSNKMLGKIYDYVMHSLIHFQGFFVATIYCFCNNEVQTTVKRQWAQFKIQWNQRWGRR PSNRSARAAAAAAEAGDIPIYICHQEPRNEPANNQGEESAEIIPLNIIEQESSAMARALC RLPRRGLWLLLAHHLFMTTACQEANYGALLRELCLTQFQVDMEAVGETLWCDWGRTIRSY RELADCTWHMAEKLGCFWPNAEVDRFFLAVHGRYFRSCPISGRAVRDPPGSILYPFIVVP ITVTLLVTALVVWQSKRTEGIV Click to Show/Hide
|
|||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | DACRA 089 | Drug Info | Phase 1 | Type 2 diabetes | [2] | |
| Discontinued Drug(s) | [+] 4 Discontinued Drugs | + | ||||
| 1 | Davalintide | Drug Info | Discontinued in Phase 2 | Obesity | [3] | |
| 2 | AC-253 | Drug Info | Discontinued in Phase 1 | Hypertension | [4] | |
| 3 | AC-625 | Drug Info | Discontinued in Phase 1 | Hypertension | [5] | |
| 4 | AC-187 | Drug Info | Terminated | Type-2 diabetes | [6], [7] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Agonist | [+] 2 Agonist drugs | + | ||||
| 1 | DACRA 089 | Drug Info | [8] | |||
| 2 | Davalintide | Drug Info | [1] | |||
| Antagonist | [+] 1 Antagonist drugs | + | ||||
| 1 | AC-253 | Drug Info | [9] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | AC-625 | Drug Info | [9] | |||
| 2 | AC-187 | Drug Info | [7] | |||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Olcegepant | Ligand Info | |||||
| Structure Description | Crystal structure of a CGRP receptor ectodomain heterodimer with bound high affinity inhibitor | PDB:6ZIS | ||||
| Method | X-ray diffraction | Resolution | 1.73 Å | Mutation | No | [10] |
| PDB Sequence |
SAKIEEGKLV
10 IWINGDKGYN20 GLAEVGKKFE30 KDTGIKVTVE40 HPDKLEEKFP50 QVAATGDGPD 60 IIFWAHDRFG70 GYAQSGLLAE80 ITPDKAFQDK90 LYPFTWDAVR100 YNGKLIAYPI 110 AVEALSLIYN120 KDLLPNPPKT130 WEEIPALDKE140 LKAKGKSALM150 FNLQEPYFTW 160 PLIAADGGYA170 FKYENGKYDI180 KDVGVDNAGA190 KAGLTFLVDL200 IKNKHMNADT 210 DYSIAEAAFN220 KGETAMTING230 PWAWSNIDTS240 KVNYGVTVLP250 TFKGQPSKPF 260 VGVLSAGINA270 ASPNKELAKE280 FLENYLLTDE290 GLEAVNKDKP300 LGAVALKSYE 310 EELAKDPRIA320 ATMENAQKGE330 IMPNIPQMSA340 FWYAVRTAVI350 NAASGRQTVD 360 EALKDAQTNA370 AAEFTTACQE1029 ANYGALLREL1039 CLTQFQVDME1049 AVGETLWCDW 1059 GRTIRSYREL1069 ADCTWHMAEK1079 LGCFWPNAEV1089 DRFFLAVHGR1099 YFRSCPISIQ 2033 LGVTRNKIMT2043 AQYECYQKIM2053 QDPIQQGVYC2065 QRTWDGWLCW2075 NDVAAGTESM 2085 QLCPDYFQDF2095 DPSEKVTKIC2105 DQDGNWFRHP2115 ASQRTWTDYT2125 QCNVNTHEKV 2135 KTALNLFYL
|
|||||
|
|
ALA1070
3.531
ASP1071
2.758
TRP1074
3.319
HIS1075
3.681
TRP1084
3.411
PRO1085
3.952
THR2037
4.999
ARG2038
3.872
ILE2041
3.723
MET2042
3.836
ASP2070
3.398
GLY2071
3.211
|
|||||
| 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 | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Vascular smooth muscle contraction | |||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Davalintide (AC2307), a novel amylin-mimetic peptide: enhanced pharmacological properties over native amylin to reduce food intake and body weight. Int J Obes (Lond). 2010 Feb;34(2):385-95. | |||||
| REF 2 | ClinicalTrials.gov (NCT03907202) A Clinical Study to Evaluate the Safety, Tolerability, PK, PD, and Efficacy of KBP-089 in Patients With T2DM. U.S. National Institutes of Health. | |||||
| REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025197) | |||||
| REF 4 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001605) | |||||
| REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002980) | |||||
| REF 6 | 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: 689). | |||||
| REF 7 | Antagonist of the amylin receptor blocks beta-amyloid toxicity in rat cholinergic basal forebrain neurons. J Neurosci. 2004 Jun 16;24(24):5579-84. | |||||
| REF 8 | A novel dual amylin and calcitonin receptor agonist, KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference. Br J Pharmacol. 2017 Apr;174(7):591-602. | |||||
| REF 9 | Biotechnology and Its Application in Pharmacy. Kulkarn. 2002. Page157. | |||||
| REF 10 | Structure-Based Drug Discovery of N-((R)-3-(7-Methyl-1H-indazol-5-yl)-1-oxo-1-(((S)-1-oxo-3-(piperidin-4-yl)-1-(4-(pyridin-4-yl)piperazin-1-yl)propan-2-yl)amino)propan-2-yl)-2'-oxo-1',2'-dihydrospiro[piperidine-4,4'-pyrido[2,3-d][1,3]oxazine]-1-carboxamide (HTL22562): A Calcitonin Gene-Related Peptide Receptor Antagonist for Acute Treatment of Migraine. J Med Chem. 2020 Jul 23;63(14):7906-7920. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.