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

General Information of Drug (ID: DMB0TNL)

• Drug Name: AC-201 Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Type-2 diabetes	5A11	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 26248
  TTD Drug ID: DMB0TNL

Molecule-Related Drug Atlas

Drug(s) Targeting Interleukin-1 beta (IL1B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Glucosamine	DM4ZLFD	Osteoarthritis	FA00-FA05	Approved	[2]
Rilonacept	DMGLUQS	Arthritis	FA20	Approved	[3]
Gallium nitrate	DMF9O6B	Hypercalcaemia	5B91.0	Approved	[4]
Canakinumab	DM8HLO5	Autosomal dominant familial periodic fever		Approved	[5]
Diacerein	DMN2Q5I	N. A.	N. A.	Phase 4	[6]
XOMA 052	DMOKQV7	Type-2 diabetes	5A11	Phase 3	[7]
ABT-981	DM6PTIX	Osteoarthritis	FA00-FA05	Phase 2	[8]
LY-2189102	DMU81BH	Cardiovascular disease	BA00-BE2Z	Phase 2	[9]
TT-301	DM4QV8Y	Alzheimer disease	8A20	Phase 1	[10]
CYT-013-IL1bQb	DMNICD4	Inflammation	1A00-CA43.1	Phase 1	[11]

Drug(s) Targeting Caspase-1 (CASP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Belnacasan	DM2Q50G	Epilepsy	8A60-8A68	Phase 2	[12]
PRALNACASAN	DM73UTG	Rheumatoid arthritis	FA20	Phase 2	[13]
Nivocasan	DMUX8JZ	Fibrosis	GA14-GC01	Phase 2	[14]
Ac-YVAD-FMK	DM7K256	Allergic contact dermatitis	EK00	Patented	[15]
Ac-YVAD-cmk	DMA1RVN	Allergic contact dermatitis	EK00	Patented	[15]
VE-16084	DMHG70W	Rheumatoid arthritis	FA20	Terminated	[16]
L-709049	DMQZW6D	N. A.	N. A.	Terminated	[17]
SDZ-224-015	DMY1KE8	Rheumatoid arthritis	FA20	Terminated	[18]
M826	DM9NPE4	Discovery agent	N.A.	Investigative	[19]
YVAD	DM24LNB	Discovery agent	N.A.	Investigative	[20]

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]
Interleukin-1 beta (IL1B)	TTRYK0X	IL1B_HUMAN	Inhibitor	[1]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Glucosamine inhibits IL-1beta-mediated IL-8 production in prostate cancer cells by MAPK attenuation. J Cell Biochem. 2009 Oct 1;108(2):489-98.
• [3] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [4] Elimination of arthritis pain and inflammation for over 2 years with a single 90 min, topical 14% gallium nitrate treatment: case reports and revie... Med Hypotheses. 2005;65(6):1136-41.
• [5] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [6] Non-surgical treatment of osteoarthritis of large joints - new aspects. Wien Med Wochenschr. 2009;159(3-4):76-86.
• [7] Gevokizumab, an anti-IL-1beta mAb for the potential treatment of type 1 and 2 diabetes, rheumatoid arthritis and cardiovascular disease. Curr Opin Mol Ther. 2010 Dec;12(6):755-69.
• [8] Generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-Ig(TM)) molecule that specifically and potently neutralizes both IL-1alpha and IL-1beta. MAbs. 2015;7(3):605-19.
• [9] Double-blind, randomized study evaluating the glycemic and anti-inflammatory effects of subcutaneous LY2189102, a neutralizing IL-1beta antibody, in patients with type 2 diabetes. Diabetes Care. 2013Aug;36(8):2239-46.
• [10] A Swell in the Armamentarium of Antiepileptic Drug Targets. Epilepsy Curr. 2011 Nov-Dec; 11(6): 172-176.
• [11] 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: 2623).
• [12] (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.
• [13] 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.
• [14] Combined effects of an antioxidant and caspase inhibitor on the reversal of hepatic fibrosis in rats. Apoptosis. 2013 Dec;18(12):1481-91.
• [15] Caspase inhibitors: a review of recently patented compounds (2013-2015).Expert Opin Ther Pat. 2018 Jan;28(1):47-59.
• [16] Interleukin-1 beta converting enzyme inhibition blocks progression of type II collagen-induced arthritis in mice. Cytokine. 1996 May;8(5):377-86.
• [17] 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.
• [18] 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.
• [19] Novel pyrazinone mono-amides as potent and reversible caspase-3 inhibitors. Bioorg Med Chem Lett. 2005 Feb 15;15(4):1173-80.
• [20] Mice deficient in interleukin-1beta converting enzyme resist anorexia induced by central lipopolysaccharide. Am J Physiol. 1999 Nov;277(5 Pt 2):R1435-43.