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

General Information of Drug (ID: DMQZW6D)

• Drug Name: L-709049 Drug Info
• Synonyms: Ac-Yvad-cho; L-709049; 143313-51-3; Acetyl-tyrosyl-valyl-alanyl-aspartal; Caspase-1 Inhibitor I; CHEMBL37630; Ac-Tyr-Val-Ala-Asp-H; IL-1beta Converting Enzyme (ICE) Inhibitor I; acetyl-Tyr-Val-Ala-Asp-aldehyde; N-acetyl-Tyr-Val-Ala-Asp-aldehyde; (3S)-3-[(2S)-2-[(2S)-2-[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanamido]-3-methylbutanamido]propanamido]-4-oxobutanoic acid; Ac-Tyr-Val-Ala-Asp-Aldehyde; AC1NSK2K; SCHEMBL4349143; BDBM10355; MolPort-016-580-695; N-acetyl-Tyr-Val-Ala-Asp aldehyde; ZINC3915255; 1600AH; NCGC00167338-01
• Cross-matching ID:
  PubChem CID: 5311139
  ChEBI ID: CHEMBL37630
  TTD Drug ID: DMQZW6D

Molecule-Related Drug Atlas

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	[3]
Belnacasan	DM2Q50G	Epilepsy	8A60-8A68	Phase 2	[4]
PRALNACASAN	DM73UTG	Rheumatoid arthritis	FA20	Phase 2	[5]
Nivocasan	DMUX8JZ	Fibrosis	GA14-GC01	Phase 2	[6]
Ac-YVAD-FMK	DM7K256	Allergic contact dermatitis	EK00	Patented	[7]
Ac-YVAD-cmk	DMA1RVN	Allergic contact dermatitis	EK00	Patented	[7]
VE-16084	DMHG70W	Rheumatoid arthritis	FA20	Terminated	[8]
SDZ-224-015	DMY1KE8	Rheumatoid arthritis	FA20	Terminated	[9]
M826	DM9NPE4	Discovery agent	N.A.	Investigative	[10]
YVAD	DM24LNB	Discovery agent	N.A.	Investigative	[11]

Drug(s) Affected By Apoptotic protease-activating factor 1 (APAF1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[12]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[13]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[14]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[15]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[16]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[17]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[18]
Acocantherin	DM7JT24	Atrial fibrillation	BC81.3	Approved	[19]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[20]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[21]

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]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Apoptotic protease-activating factor 1 (APAF1)	OTJWIVY0	APAF_HUMAN	Gene/Protein Processing	[2]

References

• [1] 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.
• [2] Nano-sized iron particles may induce multiple pathways of cell death following generation of mistranscripted RNA in human corneal epithelial cells. Toxicol In Vitro. 2017 Aug;42:348-357.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] (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.
• [5] 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.
• [6] Combined effects of an antioxidant and caspase inhibitor on the reversal of hepatic fibrosis in rats. Apoptosis. 2013 Dec;18(12):1481-91.
• [7] Caspase inhibitors: a review of recently patented compounds (2013-2015).Expert Opin Ther Pat. 2018 Jan;28(1):47-59.
• [8] Interleukin-1 beta converting enzyme inhibition blocks progression of type II collagen-induced arthritis in mice. Cytokine. 1996 May;8(5):377-86.
• [9] 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.
• [10] Novel pyrazinone mono-amides as potent and reversible caspase-3 inhibitors. Bioorg Med Chem Lett. 2005 Feb 15;15(4):1173-80.
• [11] Mice deficient in interleukin-1beta converting enzyme resist anorexia induced by central lipopolysaccharide. Am J Physiol. 1999 Nov;277(5 Pt 2):R1435-43.
• [12] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
• [13] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [14] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [15] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [16] Comparison of Drug Metabolism and Its Related Hepatotoxic Effects in HepaRG, Cryopreserved Human Hepatocytes, and HepG2 Cell Cultures. Biol Pharm Bull. 2018 May 1;41(5):722-732. doi: 10.1248/bpb.b17-00913. Epub 2018 Feb 14.
• [17] Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol. 2016 Mar;31(3):314-28.
• [18] Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact. 2010 Jul 30;186(2):127-34. doi: 10.1016/j.cbi.2010.04.027. Epub 2010 May 21.
• [19] Ouabain induces apoptotic cell death in human prostate DU 145 cancer cells through DNA damage and TRAIL pathways. Environ Toxicol. 2019 Dec;34(12):1329-1339. doi: 10.1002/tox.22834. Epub 2019 Aug 21.
• [20] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [21] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.