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

General Information of Drug (ID: DMJ48AB)

• Drug Name: ARRY-797 Drug Info
• Synonyms: CHEMBL1088750; ARRY-797; SCHEMBL222635; ARRY-371797; BDBM50314072

Indication

Disease Entry	ICD 11	Status	REF
Dilated cardiomyopathy	BC43.0	Phase 2	[1] , [2]
Osteoarthritis	FA00-FA05	Phase 2	[3]
Pain	MG30-MG3Z	Phase 2	[3]

• Therapeutic Class: Analgesics
• Cross-matching ID:
  PubChem CID: 46883775
  TTD Drug ID: DMJ48AB

Molecule-Related Drug Atlas

Drug(s) Targeting Stress-activated protein kinase (p38)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BMS-582949	DMGYXFP	Atherosclerosis	BD40	Phase 2	[5]
AZD7624	DMEW3K9	Chronic obstructive pulmonary disease	CA22	Phase 2	[6]
GSK2269557	DMIN0SV	Asthma	CA23	Phase 2	[7]
TAK-715	DMZKPI8	Rheumatoid arthritis	FA20	Phase 2	[8]
LY-2228820	DMHXTNW	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[9]
ARRY-614	DMXD93K	Arthritis	FA20	Discontinued in Phase 1	[10]
TA-5493	DMFES2K	Inflammation	1A00-CA43.1	Discontinued in Phase 1	[11]
AZD-6703	DM9KLD3	Rheumatoid arthritis	FA20	Discontinued in Phase 1	[12]
AVE-9940	DMIB3AT	Rheumatoid arthritis	FA20	Discontinued in Phase 1	[13]
SB-281832	DMYTAJW	Asthma	CA23	Discontinued in Phase 1	[14]

Drug(s) Targeting MAP kinase p38 (MAPK12)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SM-101	DMFX9O6	Idiopathic thrombocytopenic purpura	3B64.10	Approved (orphan drug)	[15]
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[16]
KC706	DMBX6C7	Cardiovascular disease	BA00-BE2Z	Discontinued in Phase 2	[17]
SB 235699	DMNH8XU	Psoriasis vulgaris	EA90	Discontinued in Phase 1	[18]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[19]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[19]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[20]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[19]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[21]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
MAP kinase p38 (MAPK12)	TTYT93M	MK12_HUMAN	Inhibitor	[4]
Stress-activated protein kinase (p38)	TTWELHI	NOUNIPROTAC	Inhibitor	[1]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019505)
• [4] Array BioPharmas ARRY-797 Meets Primary Endpoint in Clinical Proof of Concept Trial in Osteoarthritis Patients Whose Pain is Poorly Controlled by NSAIDs
• [5] Synthesis and evaluation of carbamoylmethylene linked prodrugs of BMS-582949, a clinical p38alpha inhibitor. Bioorg Med Chem Lett. 2013 May 15;23(10):3028-33.
• [6] Investigational p38 inhibitors for the treatment of chronic obstructive pulmonary disease. Expert Opin Investig Drugs. 2015 Mar;24(3):383-92.
• [7] Evaluation of WO2012032067 and WO2012055846: two selective PI3Kdelta inhibitors, which is GSK-2269557. Expert Opin Ther Pat. 2012 Aug;22(8):965-70.
• [8] Inhibition of Wnt/beta-catenin signaling by p38 MAP kinase inhibitors is explained by cross-reactivity with casein kinase Idelta/ . Chem Biol. 2011 Apr 22;18(4):485-94.
• [9] 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. (Ligand id: 7959).
• [10] Cmpany report (Arraybiopharma)
• [11] US patent application no. 2008,0269,123, Methods for treating polycystic kidney disease (pkd) or other cyst forming diseases.
• [12] The discovery of N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzamide (AZD6703), a clinical p38alpha MAP kinase inhibitor for the treatment of inflammatory diseases. Bioorg Med Chem Lett. 2012 Jun 15;22(12):3879-83.
• [13] US patent application no. 2008,0119,498, Therapeutic agent for pruritus comprising p38 map kinase inhibitor as the active ingredient.
• [14] p38 MAPK inhibitors ameliorate target organ damage in hypertension: Part 1. p38 MAPK-dependent endothelial dysfunction and hypertension. J Pharmacol Exp Ther. 2003 Dec;307(3):932-8.
• [15] Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63.
• [16] P38 MAP kinase inhibitors as potential therapeutics for the treatment of joint degeneration and pain associated with osteoarthritis. J Inflamm (Lond). 2008 Dec 4;5:22.
• [17] KC706, an Oral p38 MAP Kinase Inhibitor, Increases HDL-C. Circulation. 2007;116:II_126.
• [18] Synthesis and structure-activity relationship of aminobenzophenones. A novel class of p38 MAP kinase inhibitors with high antiinflammatory activity. J Med Chem. 2003 Dec 18;46(26):5651-62.
• [19] Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
• [20] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [21] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.