Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM9NPE4)

• Drug Name: M826 Drug Info
• Synonyms: compound 4sx

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 9851134
  TTD Drug ID: DM9NPE4

Molecule-Related Drug Atlas

Drug(s) Targeting Caspase-4 (CASP4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
casp 4 inhib	DMW6P4A	Discovery agent	N.A.	Investigative	[2]

Drug(s) Targeting Caspase-3 (CASP3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PAC1	DMYQUIP	Anaplastic astrocytoma	2A00.0	Phase 1	[3]
Isoquinoline-1,3,4(2H)-trione	DMT4RI2	Discovery agent	N.A.	Investigative	[4]
Glionitrin A	DM98CSW	Solid tumour/cancer	2A00-2F9Z	Investigative	[5]
Ac-DEVD-CHO	DMW02H7	Discovery agent	N.A.	Investigative	[6]
5-(piperidin-1-ylsulfonyl)indoline-2,3-dione	DMT60AM	Discovery agent	N.A.	Investigative	[7]
SJ-8002	DMEQBU2	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
AZ10417808	DMNO6PL	Discovery agent	N.A.	Investigative	[9]
2-phenethylisoquinoline-1,3,4-trione	DMPWG21	Discovery agent	N.A.	Investigative	[4]
2-benzylisoquinoline-1,3,4-trione	DME7SAV	Discovery agent	N.A.	Investigative	[4]
2-(4-methoxy-benzyl)isoquinoline-1,3,4-trione	DMHAE31	Discovery agent	N.A.	Investigative	[4]

Drug(s) Targeting Caspase-7 (CASP7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
isatin sulfonamide 34	DM21Y8J	Cystic fibrosis	CA25	Clinical trial	[2]

Drug(s) Targeting Caspase-1 (CASP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AC-201	DMB0TNL	Type-2 diabetes	5A11	Phase 2	[10]
Belnacasan	DM2Q50G	Epilepsy	8A60-8A68	Phase 2	[11]
PRALNACASAN	DM73UTG	Rheumatoid arthritis	FA20	Phase 2	[12]
Nivocasan	DMUX8JZ	Fibrosis	GA14-GC01	Phase 2	[13]
Ac-YVAD-FMK	DM7K256	Allergic contact dermatitis	EK00	Patented	[14]
Ac-YVAD-cmk	DMA1RVN	Allergic contact dermatitis	EK00	Patented	[14]
VE-16084	DMHG70W	Rheumatoid arthritis	FA20	Terminated	[15]
L-709049	DMQZW6D	N. A.	N. A.	Terminated	[16]
SDZ-224-015	DMY1KE8	Rheumatoid arthritis	FA20	Terminated	[17]
YVAD	DM24LNB	Discovery agent	N.A.	Investigative	[18]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Caspase-1 (CASP1)	TTCQIBE	CASP1_HUMAN	Inhibitor	[1]
Caspase-3 (CASP3)	TTPF2QI	CASP3_HUMAN	Inhibitor	[1]
Caspase-4 (CASP4)	TT3VZ8D	CASP4_HUMAN	Inhibitor	[1]
Caspase-5 (CASP5)	TTWR48J	CASP5_HUMAN	Inhibitor	[1]
Caspase-7 (CASP7)	TTM7Y45	CASP7_HUMAN	Inhibitor	[1]

References

• [1] Novel pyrazinone mono-amides as potent and reversible caspase-3 inhibitors. Bioorg Med Chem Lett. 2005 Feb 15;15(4):1173-80.
• [2] Potent and selective nonpeptide inhibitors of caspases 3 and 7. J Med Chem. 2001 Jun 7;44(12):2015-26.
• [3] Small-molecule activation of procaspase-3 to caspase-3 as a personalized anticancer strategy. Nat Chem Biol. 2006 Oct;2(10):543-50.
• [4] Design, synthesis, and biological evaluation of isoquinoline-1,3,4-trione derivatives as potent caspase-3 inhibitors. J Med Chem. 2006 Mar 9;49(5):1613-23.
• [5] Glionitrin A, a new diketopiperazine disulfide, activates ATM-ATR-Chk1/2 via 53BP1 phosphorylation in DU145 cells and shows antitumor effect in xenograft model. Biol Pharm Bull. 2014;37(3):378-86.
• [6] Synthesis and evaluation of vinyl sulfones as caspase-3 inhibitors. A structure-activity study. Eur J Med Chem. 2010 Sep;45(9):3858-63.
• [7] Design, synthesis, and discovery of novel non-peptide inhibitor of Caspase-3 using ligand based and structure based virtual screening approach. Bioorg Med Chem. 2009 Aug 15;17(16):6040-7.
• [8] 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. (Target id: 1619).
• [9] Novel small molecule inhibitors of caspase-3 block cellular and biochemical features of apoptosis. J Pharmacol Exp Ther. 2003 Jan;304(1):433-40.
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] (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-tetrahydr... J Pharmacol Exp Ther. 2007 May;321(2):509-16.
• [12] Pralnacasan, an inhibitor of interleukin-1beta converting enzyme, reduces joint damage in two murine models of osteoarthritis. Osteoarthritis Cartilage. 2003 Oct;11(10):738-46.
• [13] Combined effects of an antioxidant and caspase inhibitor on the reversal of hepatic fibrosis in rats. Apoptosis. 2013 Dec;18(12):1481-91.
• [14] Caspase inhibitors: a review of recently patented compounds (2013-2015).Expert Opin Ther Pat. 2018 Jan;28(1):47-59.
• [15] Interleukin-1 beta converting enzyme inhibition blocks progression of type II collagen-induced arthritis in mice. Cytokine. 1996 May;8(5):377-86.
• [16] Succinic acid amides as P2-P3 replacements for inhibitors of interleukin-1beta converting enzyme (ICE or caspase 1). Bioorg Med Chem Lett. 2010 Sep 1;20(17):5184-90.
• [17] Reduction 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.
• [18] Mice deficient in interleukin-1beta converting enzyme resist anorexia induced by central lipopolysaccharide. Am J Physiol. 1999 Nov;277(5 Pt 2):R1435-43.