Target Information

Target General Infomation
Target ID
T98269
Former ID
TTDR00434
Target Name
Interleukin-1 beta convertase
Gene Name
CASP1
Synonyms
CASP-1; Caspase-1; ICE; IL-1 beta converting enzyme; IL-1BC; Interleukin-1 beta converting enzyme; P45; CASP1
Target Type
Clinical Trial
Disease Epilepsy [ICD10: G40]
Fibrosis [ICD9: 709.2; ICD10: L90.5]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Function
Thiol protease that cleavesIL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis.
BioChemical Class
Peptidase
Target Validation
T98269
UniProt ID
P29466
EC Number
EC 3.4.22.36
Sequence
MADKVLKEKRKLFIRSMGEGTINGLLDELLQTRVLNKEEMEKVKRENATVMDKTRALIDS
VIPKGAQACQICITYICEEDSYLAGTLGLSADQTSGNYLNMQDSQGVLSSFPAPQAVQDN
PAMPTSSGSEGNVKLCSLEEAQRIWKQKSAEIYPIMDKSSRTRLALIICNEEFDSIPRRT
GAEVDITGMTMLLQNLGYSVDVKKNLTASDMTTELEAFAHRPEHKTSDSTFLVFMSHGIR
EGICGKKHSEQVPDILQLNAIFNMLNTKNCPSLKDKPKVIIIQACRGDSPGVVWFKDSVG
VSGNLSLPTTEEFEDDAIKKAHIEKDFIAFCSSTPDNVSWRHPTMGSVFIGRLIEHMQEY
ACSCDVEEIFRKVRFSFEQPDGRAQMPTTERVTLTRCFYLFPGH
Drugs and Mode of Action
Drug(s) Belnacasan Drug Info Phase 2 Epilepsy [526728]
Nivocasan Drug Info Phase 2 Fibrosis [532482]
PRALNACASAN Drug Info Phase 2 Rheumatoid arthritis [526728], [541602]
L-709049 Drug Info Terminated Discovery agent [545779]
SDZ-224-015 Drug Info Terminated Rheumatoid arthritis [546056]
VE-16084 Drug Info Terminated Rheumatoid arthritis [534169]
Inhibitor Belnacasan Drug Info [527677], [528662]
L-709049 Drug Info [531052]
M826 Drug Info [527416]
VE-16084 Drug Info [534169]
YVAD Drug Info [534926]
Z-VAD-CHO Drug Info [527847]
Z-YVAD-CHO Drug Info [527847]
Z-YVAD-FMK Drug Info [526372]
Modulator Nivocasan Drug Info [532482]
PRALNACASAN Drug Info [526728]
SDZ-224-015 Drug Info [533644]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway NOD-like receptor signaling pathway
Cytosolic DNA-sensing pathway
Amyotrophic lateral sclerosis (ALS)
Salmonella infection
Pertussis
Legionellosis
Influenza A
NetPath Pathway TCR Signaling Pathway
IL2 Signaling Pathway
TGF_beta_Receptor Signaling Pathway
Pathway Interaction Database IL1-mediated signaling events
Direct p53 effectors
IFN-gamma pathway
Cellular roles of Anthrax toxin
Reactome NOD1/2 Signaling Pathway
Interleukin-1 processing
The NLRP3 inflammasome
WikiPathways MAPK Signaling Pathway
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
Apoptosis
Amyotrophic lateral sclerosis (ALS)
Parkin-Ubiquitin Proteasomal System pathway
Interleukin-1 processing
Apoptosis Modulation and Signaling
NOD pathway
References
Ref 526728Pralnacasan, an inhibitor of interleukin-1beta converting enzyme, reduces joint damage in two murine models of osteoarthritis. Osteoarthritis Cartilage. 2003 Oct;11(10):738-46.
Ref 532482Combined effects of an antioxidant and caspase inhibitor on the reversal of hepatic fibrosis in rats. Apoptosis. 2013 Dec;18(12):1481-91.
Ref 534169Interleukin-1 beta converting enzyme inhibition blocks progression of type II collagen-induced arthritis in mice. Cytokine. 1996 May;8(5):377-86.
Ref 541602(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: 6467).
Ref 545779Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004677)
Ref 546056Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006085)
Ref 526372Different molecular events account for butyrate-induced apoptosis in two human colon cancer cell lines. J Nutr. 2002 Jul;132(7):1812-8.
Ref 526728Pralnacasan, an inhibitor of interleukin-1beta converting enzyme, reduces joint damage in two murine models of osteoarthritis. Osteoarthritis Cartilage. 2003 Oct;11(10):738-46.
Ref 527416Novel pyrazinone mono-amides as potent and reversible caspase-3 inhibitors. Bioorg Med Chem Lett. 2005 Feb 15;15(4):1173-80.
Ref 527677IL-converting enzyme/caspase-1 inhibitor VX-765 blocks the hypersensitive response to an inflammatory stimulus in monocytes from familial cold autoinflammatory syndrome patients. J Immunol. 2005 Aug 15;175(4):2630-4.
Ref 527847Bioorg Med Chem Lett. 2006 Feb;16(3):559-62. Epub 2005 Nov 4.Tethering identifies fragment that yields potent inhibitors of human caspase-1.
Ref 528662(S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and IL-18. J Pharmacol Exp Ther. 2007 May;321(2):509-16. Epub 2007 Feb 8.
Ref 531052Bioorg Med Chem Lett. 2010 Sep 1;20(17):5184-90. Epub 2010 Jul 8.Succinic acid amides as P2-P3 replacements for inhibitors of interleukin-1beta converting enzyme (ICE or caspase 1).
Ref 532482Combined effects of an antioxidant and caspase inhibitor on the reversal of hepatic fibrosis in rats. Apoptosis. 2013 Dec;18(12):1481-91.
Ref 533644Reduction of inflammation and pyrexia in the rat by oral administration of SDZ 224-015, an inhibitor of the interleukin-1 beta converting enzyme. Br J Pharmacol. 1995 Jun;115(4):601-6.
Ref 534169Interleukin-1 beta converting enzyme inhibition blocks progression of type II collagen-induced arthritis in mice. Cytokine. 1996 May;8(5):377-86.
Ref 534926Mice deficient in interleukin-1beta converting enzyme resist anorexia induced by central lipopolysaccharide. Am J Physiol. 1999 Nov;277(5 Pt 2):R1435-43.

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