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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 ![]() |
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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 ![]() |
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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 ![]() |
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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 ![]() |
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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]. |
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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 04/03/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2190.