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receptor interacting serine/threonine kinase 1

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2189

Nomenclature: receptor interacting serine/threonine kinase 1

Abbreviated Name: RIPK1

Family: Receptor interacting protein kinase (RIPK) family

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 671 6p25.2 RIPK1 receptor interacting serine/threonine kinase 1
Mouse - 656 13 14.01 cM Ripk1 receptor (TNFRSF)-interacting serine-threonine kinase 1
Rat - 658 17 p12 Ripk1 receptor interacting serine/threonine kinase 1
Previous and Unofficial Names Click here for help
RIP | Rip1 | receptor (TNFRSF)-interacting serine-threonine kinase 1
Database Links Click here for help
Alphafold
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of RIP1 kinase in complex with necrostatin-4
PDB Id:  4ITJ
Resolution:  1.8Å
Species:  Human
References:  32
Image of receptor 3D structure from RCSB PDB
Description:  X-ray structure of Receptor Interacting Protein 1 (RIP1)kinase domain with a 1-aminoisoquinoline inhibitor
PDB Id:  4NEU
Resolution:  2.57Å
Species:  Human
References:  11
Enzyme Reaction Click here for help
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
RIPK1 inhibitor 22b Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pKd 17
pKd 8.4 (Kd 4.4x10-9 M) [17]
Description: Binding affinity value.
necrostatin-1s Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 7.4 pKd 8
pKd 7.4 (Kd 3.7x10-8 M) [8]
Description: Affinity constant measured at 37oC.
SZM594 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.0 pKd 4
pKd 7.0 (Kd 9.7x10-8 M) [4]
Description: Determined in a KINOMEscan assay.
6E11 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 6.4 pKd 9
pKd 6.4 (Kd 4x10-7 M) [9]
Description: Binding constant measured at 37oC.
TAK-632 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.3 pKd 4
pKd 6.3 (Kd 4.8x10-7 M) [4]
Description: Binding constant determined by KINOMEscan assay.
RIPK3 inhibitor 42 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition <5.3 pKd 33
pKd <5.3 (Kd >5x10-6 M) [33]
GSK963 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 9.1 pIC50 3
pIC50 9.1 (IC50 8x10-10 M) [3]
Description: Inhibition of RIPK1 kinase activity in an ADP-Glo kinase assay measuring autophosphorylation of RIPK1 kinase domain in vitro; value calculated using a tight binding fit calculation.
GSK2982772 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.0 pIC50 12
pIC50 9.0 (IC50 1x10-9 M) [12]
compound 21 [PMID: 24900635] Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 8.9 pIC50 11
pIC50 8.9 (IC50 1.3x10-9 M) [11]
GSK'547 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 8.0 pIC50 2
pIC50 8.0 (IC50 1x10-8 M) [2]
Description: Determined in an in vitro fluorescent polarization based binding assay.
eclitasertib Small molecule or natural product Hs Inhibition 6.0 – 10.0 pIC50 10
pIC50 6.0 – 10.0 (IC50 1x10-6 – 1x10-10 M) [10]
Description: Binned value determined in a fluorescent polarization hRIPK1 binding assay.
RIPK1 inhibitor 22b Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 pIC50 17
pIC50 8.0 (IC50 1.1x10-8 M) [17]
Description: Inhibition of RIPK1 enzymatic activity in vitro determined using Eurofins' KinaseProfiler assay.
ponatinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.9 pIC50 19
pIC50 7.9 (IC50 1.2x10-8 M) [19]
Description: Inhibition of recombinant RIPK1 in an in vitro ADP-Glo assay (Promega).
RIPA-56 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 7.9 pIC50 22
pIC50 7.9 (IC50 1.3x10-8 M) [22]
Description: Inhibition of RIPK1 enzymatic activity in vitro.
compound 27 [PMID: 24900635] Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 7.9 pIC50 11
pIC50 7.9 (IC50 1.3x10-8 M) [11]
Description: IN an ADP-glo assay that measures the ADP produced during autophosphorylation of RIPK1 catalytic domain.
PN10 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.1 pIC50 19
pIC50 7.1 (IC50 9x10-8 M) [19]
Description: Inhibition of recombinant human RIPK1 using ADP-Glo assay.
necrostatin-1 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.3 pIC50 7
pIC50 6.3 (IC50 4.9x10-7 M) [7]
Description: Measuring inhibition of cellular necrosis in TNFα-treated FADD-deficient Jurkat cells.
RIPK3 inhibitor 18 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.3 pIC50 13
pIC50 5.3 (IC50 5.5x10-6 M) [13]
DiscoveRx KINOMEscan® screen Click here for help
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: 6,31

Key to terms and symbols Click column headers to sort
Target used in screen: RIPK1
Ligand Sp. Type Action Value Parameter
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.7 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 7.2 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.7 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 6.6 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 6.6 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 6.5 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
quizartinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 5.9 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [20,23,25,28]. RIPK1 and RIPK2 appear to be critical mediators of intestinal homeostasis and drivers of intestinal inflammation [14]. RIPK-targeting necroptosis inhibitors are being developed to target inflammation mediated disorders [15], including the development of novel therapeutics for the treatment of TNF-induced systemic inflammatory response syndrome (SIRS) and sepsis, as well as cancer [3,11,18,29]. RIPK1 inhibitors are also being evaluated in clinical trials for autoimmune diseases including psoriasis, rheumatoid arthritis and ulcerative colitis (e.g. GSK2982772).

In the immuno-oncology setting RIPK1 inhibitors are being investigated as adjuncts to checkpoint inhibiting drugs like pembrolizumab, with the goal of enhancing the anti-tumour immune system reactivating effects of checkpoint inhibition. For example, GlaxoSmithKline had an experimental RIPK1 inhibitor known by the research code GSK095, that had shown exactly this effect in preclinical models of pancreatic cancer. However, GSK terminated the GSK095 programme in early 2020, so the efficacy of this mechanism was never established in human subjects.

There were two independent reports of human RIPK1 deficiency as a causaul factor in patients with severe immunodeficiency in 2018: Cuchet-Lourenço et al. [5] and Li et al. [16] identified biallelic loss-of-function mutations in RIPK1 genes of patients with primary immunodeficiency and notably, early-onset intestinal immune dysregulation amongst other signs and symptoms of immunodeficiency (recurrent infection, progressive polyarthritis, lymphopenia, altered cytokine production). These studies highlight the importance of RIPK1 function as a key regulator of human immune and intestinal homeostasis, and also raise awareness of the possible undesireable outcomes when targeting RIPK1 for therapeutic benefit. SARS-CoV-2/COVID-19
RNA viruses activate the NLRP3 inflammasome and promote IL-1β production via a virus-induced pathway that initiates assembly of the RIPK1/3 complex, triggers activation of the GTPase DRP1, and drives mitochondrial damage and eventually, activation of the NLRP3 inflammasome [21,24,30]. Indeed, RIPK1/3 inhibitors can suppress virus-induced NLRP3 inflammasome activation. It is therefore feasible that pharmacological inhibitors of RIPK1/3 could offer potential benefit as therapeutic intervention for the inflammatory effects arising from SARS-CoV-2 infection. It should be noted that some activation of NLRP3 is essential for an effective innate antiviral response (including clearance of the virus and induction of lung tissue repair) [1,26-27], so the timing of administration of any inhibitors would be crucial, to avoid blocking the innate response and potentially causing harm [30].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:0050729 positive regulation of inflammatory response IMP
click arrow to show/hide IEA associations
GO:0006954 inflammatory response IEA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0070231 T cell apoptotic process ISS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0045651 positive regulation of macrophage differentiation IMP
GO:0050729 positive regulation of inflammatory response IMP
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:0045651 positive regulation of macrophage differentiation IMP
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 8 GO processes
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway TAS
GO:0032757 positive regulation of interleukin-8 production IDA
GO:0032760 positive regulation of tumor necrosis factor production IDA
GO:0033209 tumor necrosis factor-mediated signaling pathway TAS
GO:0034612 response to tumor necrosis factor IMP
GO:0070105 positive regulation of interleukin-6-mediated signaling pathway IMP
GO:0071356 cellular response to tumor necrosis factor IDA
click arrow to show/hide IEA associations
GO:1903265 positive regulation of tumor necrosis factor-mediated signaling pathway IEA
Biologically Significant Variants Click here for help
Type:  Truncation
Species:  Human
Description:  Deleterious RIPK1 mutation identified in patient with combined immunodeficiency associated with lymphopenia.
Amino acid change:  M318IfsTer194
Nucleotide change:  954delG
References:  16
Type:  Missense mutation
Species:  Human
Description:  Deleterious RIPK1 mutation identified in patient with primary immunodeficiency characterised by very early onset irritable bowel disease (VEO-IBD).
Amino acid change:  I615T
Nucleotide change:  1844T>C
References:  16
Type:  Missense mutation
Species:  Human
Description:  Deleterious RIPK1 mutation identified in 3 patients with primary immunodeficiency characterised by very early onset irritable bowel disease (VEO-IBD).
Amino acid change:  C601Y
Nucleotide change:  1802G>A
References:  16
Type:  Missense mutation
Species:  Human
Description:  Deleterious RIPK1 mutation identified in 2 patients with primary immunodeficiency characterised by very early onset irritable bowel disease (VEO-IBD).
Amino acid change:  T645M
Nucleotide change:  1934C>T
References:  16
Type:  Deletion
Species:  Human
Description:  Exon 4 deletion causing loss of RIPK1 expression in a patient with primary immunodeficiency.
References:  5
Type:  Insertion/deletion
Species:  Human
Description:  Intron 4 insertion/deletion leading to loss of functional RIPK1 expression in a patient with primary immunodeficiency.
References:  5
Type:  Truncation
Species:  Human
Description:  Deleterious RIPK1 mutation identified in patient with combined immunodeficiency associated with lymphopenia.
Amino acid change:  Y426*
Nucleotide change:  1278C>A
References:  16

References

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1. Allen IC, Scull MA, Moore CB, Holl EK, McElvania-TeKippe E, Taxman DJ, Guthrie EH, Pickles RJ, Ting JP. (2009) The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity, 30 (4): 556-65. [PMID:19362020]

2. Anbari JM, Reilly M, Mahajan MK, Rathi C. (2020) Heterocyclic amides as kinase inhibitors for use in the treatment cancer. Patent number: WO2020044206A1. Assignee: Glaxosmithkline Intellectual Property Development Limited. Priority date: 29/08/2018. Publication date: 05/03/2020.

3. Berger SB, Harris P, Nagilla R, Kasparcova V, Hoffman S, Swift B, Dare L, Schaeffer M, Capriotti C, Ouellette M et al.. (2015) Characterization of GSK'963: a structurally distinct, potent and selective inhibitor of RIP1 kinase. Cell Death Discov, 1: 15009. [PMID:27551444]

4. Chen X, Zhuang C, Ren Y, Zhang H, Qin X, Hu L, Fu J, Miao Z, Chai Y, Liu ZG et al.. (2019) Identification of the Raf kinase inhibitor TAK-632 and its analogues as potent inhibitors of necroptosis by targeting RIPK1 and RIPK3. Br J Pharmacol, 176 (12): 2095-2108. [PMID:30825190]

5. Cuchet-Lourenço D, Eletto D, Wu C, Plagnol V, Papapietro O, Curtis J, Ceron-Gutierrez L, Bacon CM, Hackett S, Alsaleem B et al.. (2018) Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation. Science, 361 (6404): 810-813. [PMID:30026316]

6. 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]

7. Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G et al.. (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol, 4 (5): 313-21. [PMID:18408713]

8. Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, Dedhar S. (1998) Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Proc Natl Acad Sci USA, 95 (19): 11211-6. [PMID:9736715]

9. Delehouzé C, Leverrier-Penna S, Le Cann F, Comte A, Jacquard-Fevai M, Delalande O, Desban N, Baratte B, Gallais I, Faurez F et al.. (2017) 6E11, a highly selective inhibitor of Receptor-Interacting Protein Kinase 1, protects cells against cold hypoxia-reoxygenation injury. Sci Rep, 7 (1): 12931. [PMID:29018243]

10. Estrada AA, Feng JA, Fox B, Leslie CP, Lyssikatos JP, Sweeney ZK, De Vicente Fidalgo J. (2017) Compounds, compositions and methods. Patent number: WO2017136727A2. Assignee: Denali Therapeutics Inc.. Priority date: 05/02/2016. Publication date: 10/08/2017.

11. Harris PA, Bandyopadhyay D, Berger SB, Campobasso N, Capriotti CA, Cox JA, Dare L, Finger JN, Hoffman SJ, Kahler KM et al.. (2013) Discovery of Small Molecule RIP1 Kinase Inhibitors for the Treatment of Pathologies Associated with Necroptosis. ACS Med Chem Lett, 4 (12): 1238-43. [PMID:24900635]

12. Harris PA, Berger SB, Jeong JU, Nagilla R, Bandyopadhyay D, Campobasso N, Capriotti CA, Cox JA, Dare L, Dong X et al.. (2017) Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases. J Med Chem, 60 (4): 1247-1261. [PMID:28151659]

13. Hart AC, Abell L, Guo J, Mertzman ME, Padmanabha R, Macor JE, Chaudhry C, Lu H, O'Malley K, Shaw PJ et al.. (2019) Identification of RIPK3 Type II Inhibitors Using High-Throughput Mechanistic Studies in Hit Triage. ACS Med Chem Lett, Article ASAP. DOI: 10.1021/acsmedchemlett.9b00065

14. 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]

15. Kopalli SR, Kang TB, Koppula S. (2016) Necroptosis inhibitors as therapeutic targets in inflammation mediated disorders - a review of the current literature and patents. Expert Opin Ther Pat, 26 (11): 1239-1256. [PMID:27568917]

16. Li Y, Führer M, Bahrami E, Socha P, Klaudel-Dreszler M, Bouzidi A, Liu Y, Lehle AS, Magg T, Hollizeck S et al.. (2019) Human RIPK1 deficiency causes combined immunodeficiency and inflammatory bowel diseases. Proc Natl Acad Sci USA, 116 (3): 970-975. [PMID:30591564]

17. Li Y, Xiong Y, Zhang G, Zhang L, Yang W, Yang J, Huang L, Qiao Z, Miao Z, Lin G et al.. (2018) Identification of 5-(2,3-Dihydro-1 H-indol-5-yl)-7 H-pyrrolo[2,3- d]pyrimidin-4-amine Derivatives as a New Class of Receptor-Interacting Protein Kinase 1 (RIPK1) Inhibitors, Which Showed Potent Activity in a Tumor Metastasis Model. J Med Chem, 61 (24): 11398-11414. [PMID:30480444]

18. Najafov A, Chen H, Yuan J. (2017) Necroptosis and Cancer. Trends Cancer, 3 (4): 294-301. [PMID:28451648]

19. 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]

20. Newton K. (2015) RIPK1 and RIPK3: critical regulators of inflammation and cell death. Trends Cell Biol, 25 (6): 347-53. [PMID:25662614]

21. Park HS, Liu G, Liu Q, Zhou Y. (2018) Swine Influenza Virus Induces RIPK1/DRP1-Mediated Interleukin-1 Beta Production. Viruses, 10 (8). [PMID:30096906]

22. Ren Y, Su Y, Sun L, He S, Meng L, Liao D, Liu X, Ma Y, Liu C, Li S et al.. (2017) Discovery of a Highly Potent, Selective, and Metabolically Stable Inhibitor of Receptor-Interacting Protein 1 (RIP1) for the Treatment of Systemic Inflammatory Response Syndrome. J Med Chem, 60 (3): 972-986. [PMID:27992216]

23. Rickard JA, O'Donnell JA, Evans JM, Lalaoui N, Poh AR, Rogers T, Vince JE, Lawlor KE, Ninnis RL, Anderton H et al.. (2014) RIPK1 regulates RIPK3-MLKL-driven systemic inflammation and emergency hematopoiesis. Cell, 157 (5): 1175-88. [PMID:24813849]

24. Sarvestani ST, McAuley JL. (2017) The role of the NLRP3 inflammasome in regulation of antiviral responses to influenza A virus infection. Antiviral Res, 148: 32-42. [PMID:29097227]

25. 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]

26. Tate MD, Ong JDH, Dowling JK, McAuley JL, Robertson AB, Latz E, Drummond GR, Cooper MA, Hertzog PJ, Mansell A. (2016) Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition. Sci Rep, 6: 27912. [PMID:27283237]

27. Thomas PG, Dash P, Aldridge Jr JR, Ellebedy AH, Reynolds C, Funk AJ, Martin WJ, Lamkanfi M, Webby RJ, Boyd KL et al.. (2009) The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1. Immunity, 30 (4): 566-75. [PMID:19362023]

28. Vince JE, Silke J. (2016) The intersection of cell death and inflammasome activation. Cell Mol Life Sci, 73 (11-12): 2349-67. [PMID:27066895]

29. Wang T, Jin Y, Yang W, Zhang L, Jin X, Liu X, He Y, Li X. (2017) Necroptosis in cancer: An angel or a demon?. Tumour Biol, 39 (6): 1010428317711539. [PMID:28651499]

30. Wang X, Jiang W, Yan Y, Gong T, Han J, Tian Z, Zhou R. (2014) RNA viruses promote activation of the NLRP3 inflammasome through a RIP1-RIP3-DRP1 signaling pathway. Nat Immunol, 15 (12): 1126-33. [PMID:25326752]

31. 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]

32. Xie T, Peng W, Liu Y, Yan C, Maki J, Degterev A, Yuan J, Shi Y. (2013) Structural Basis of RIP1 Inhibition by Necrostatins. Structure, 21 (3): 493-9. [PMID:23473668]

33. Zhang H, Xu L, Qin X, Chen X, Cong H, Hu L, Chen L, Miao Z, Zhang W, Cai Z et al.. (2019) N-(7-Cyano-6-(4-fluoro-3-(2-(3-(trifluoromethyl)phenyl)acetamido)phenoxy)benzo[d]thiazol-2-yl)cyclopropanecarboxamide (TAK-632) Analogues as Novel Necroptosis Inhibitors by Targeting Receptor-Interacting Protein Kinase 3 (RIPK3): Synthesis, Structure-Activity Relationships, and in Vivo Efficacy. J Med Chem, 62 (14): 6665-6681. [PMID:31095385]

How to cite this page

Receptor interacting protein kinase (RIPK) family: receptor interacting serine/threonine kinase 1. Last modified on 02/11/2020. Accessed on 02/12/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2189.