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Target has curated data in GtoImmuPdb
Target id: 2190
Nomenclature: receptor interacting serine/threonine kinase 2
Abbreviated Name: RIPK2
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 540 | 8q21.3 | RIPK2 | receptor interacting serine/threonine kinase 2 | |
Mouse | - | 539 | 4 6.7 cM | Ripk2 | receptor (TNFRSF)-interacting serine-threonine kinase 2 | |
Rat | - | 539 | 5 q13 | Ripk2 | receptor-interacting serine-threonine kinase 2 |
Previous and Unofficial Names |
CARD3 | CARDIAK | CCK | RICK | RIP2 |
Database Links | |
Alphafold | O43353 (Hs), P58801 (Mm) |
BRENDA | 2.7.11.1 |
ChEMBL Target | CHEMBL5014 (Hs), CHEMBL4296021 (Mm) |
Ensembl Gene | ENSG00000104312 (Hs), ENSMUSG00000041135 (Mm), ENSRNOG00000009389 (Rn) |
Entrez Gene | 8767 (Hs), 192656 (Mm), 362491 (Rn) |
Human Protein Atlas | ENSG00000104312 (Hs) |
KEGG Enzyme | 2.7.11.1 |
KEGG Gene | hsa:8767 (Hs), mmu:192656 (Mm), rno:362491 (Rn) |
OMIM | 603455 (Hs) |
Pharos | O43353 (Hs) |
RefSeq Nucleotide | NM_003821 (Hs), NM_138952 (Mm), NM_001191865 (Rn) |
RefSeq Protein | NP_003812 (Hs), NP_620402 (Mm), NP_001178794 (Rn) |
SynPHARM | 83541 (in complex with GSK583) |
UniProtKB | O43353 (Hs), P58801 (Mm) |
Wikipedia | RIPK2 (Hs) |
Selected 3D Structures | |||||||||||||
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Enzyme Reaction | ||||
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Download all structure-activity data for this target as a CSV file
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific inhibitor tables |
DiscoveRx KINOMEscan® screen | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform. http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan Reference: 3,14 |
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Target used in screen: RIPK2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service. A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform. http://www.millipore.com/techpublications/tech1/pf3036 http://www.reactionbiology.com/webapps/main/pages/kinase.aspx Reference: 1,4 |
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Target used in screen: RIPK2/RIPK2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
Immunopharmacology Comments |
RIPK2 is involved in innate immune responses, mediating pro-inflammatory signaling from the bacterial peptidoglycan-sensing NOD1/NOD2 subfamily of innate immune pattern recognition receptors (PRRs) and signalling downstream from the Toll-like receptor (TLR) family of PRRs. Further evidence suggesting an inflammatory role is the targeting of RIPK2 (along with RIPK1/3) by the IAP family E3 ubiquitin ligases (enzymes playing a critical role in innate immunity) [10]. RIPK2 may play a role in driving a range of chronic inflammatory granulomatous diseases (e.g. either loss-of-function of NOD2 or hyperactivation of the NOD2 pathway may contribute to IBD) [8], and since it shares common functionality with RIPK1 and RIPK3, may be involved in necroptosis (a type of programmed cell death, mechanistically and morphologically distinct from apoptosis) [11]. |
Immuno Process Associations | ||
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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]
2. Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, Klevernic I, Arthur JS, Alessi DR, Cohen P. (2007) The selectivity of protein kinase inhibitors: a further update. Biochem J, 408 (3): 297-315. [PMID:17850214]
3. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
4. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]
5. Haile PA, Casillas LN, Votta BJ, Wang GZ, Charnley AK, Dong X, Bury MJ, Romano JJ, Mehlmann JF, King BW et al.. (2019) Discovery of a First-in-Class Receptor Interacting Protein 2 (RIP2) Kinase Specific Clinical Candidate, 2-((4-(Benzo[d]thiazol-5-ylamino)-6-(tert-butylsulfonyl)quinazolin-7-yl)oxy)ethyl Dihydrogen Phosphate, for the Treatment of Inflammatory Diseases. J Med Chem, 62 (14): 6482-6494. [PMID:31265286]
6. Haile PA, Votta BJ, Marquis RW, Bury MJ, Mehlmann JF, Singhaus Jr R, Charnley AK, Lakdawala AS, Convery MA, Lipshutz DB et al.. (2016) The Identification and Pharmacological Characterization of 6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a Highly Potent and Selective Inhibitor of RIP2 Kinase. J Med Chem, 59 (10): 4867-80. [PMID:27109867]
7. He X, Da Ros S, Nelson J, Zhu X, Jiang T, Okram B, Jiang S, Michellys PY, Iskandar M, Espinola S et al.. (2017) Identification of Potent and Selective RIPK2 Inhibitors for the Treatment of Inflammatory Diseases. ACS Med Chem Lett, 8 (10): 1048-1053. [PMID:29057049]
8. Jun JC, Cominelli F, Abbott DW. (2013) RIP2 activity in inflammatory disease and implications for novel therapeutics. J Leukoc Biol, 94 (5): 927-32. [PMID:23794710]
9. Najjar M, Suebsuwong C, Ray SS, Thapa RJ, Maki JL, Nogusa S, Shah S, Saleh D, Gough PJ, Bertin J et al.. (2015) Structure guided design of potent and selective ponatinib-based hybrid inhibitors for RIPK1. Cell Rep, 10 (11): 1850-60. [PMID:25801024]
10. Oberst A. (2016) Death in the fast lane: what's next for necroptosis?. FEBS J, 283 (14): 2616-25. [PMID:26395133]
11. Silke J, Rickard JA, Gerlic M. (2015) The diverse role of RIP kinases in necroptosis and inflammation. Nat Immunol, 16 (7): 689-97. [PMID:26086143]
12. Tigno-Aranjuez JT, Benderitter P, Rombouts F, Deroose F, Bai X, Mattioli B, Cominelli F, Pizarro TT, Hoflack J, Abbott DW. (2014) In vivo inhibition of RIPK2 kinase alleviates inflammatory disease. J Biol Chem, 289 (43): 29651-64. [PMID:25213858]
13. Wada Y, Kondo M, Sakairi K, Nagashima A, Tokita K, Tominaga H, Tomiyama H, Ishikawa T. (2020) Renoprotective Effects of a Novel Receptor-Interacting Protein Kinase 2 Inhibitor, AS3334034, in Uninephrectomized Adriamycin-Induced Chronic Kidney Disease Rats. J Pharmacol Exp Ther, 374 (3): 428-437. [PMID:32561685]
14. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]
15. Yang J, Shibu MA, Kong L, Luo J, BadrealamKhan F, Huang Y, Tu ZC, Yun CH, Huang CY, Ding K et al.. (2020) Design, Synthesis, and Structure-Activity Relationships of 1,2,3-Triazole Benzenesulfonamides as New Selective Leucine-Zipper and Sterile-α Motif Kinase (ZAK) Inhibitors. J Med Chem, 63 (5): 2114-2130. [PMID:31244114]
Receptor interacting protein kinase (RIPK) family: receptor interacting serine/threonine kinase 2. Last modified on 22/06/2020. Accessed on 14/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2190.