Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTWELHI)

• DTT Name: Stress-activated protein kinase (p38)
• Synonyms: p38) Stress-activated protein kinase; P38 MAPK; P38 MAP kinase; Mitogen-activated protein kinase p38
• Gene Name: NO-GeName
• DTT Type: Clinical trial target; [1]
• Related Disease:
  Arterial occlusive disease [ICD-11: BD40]
  Asthma [ICD-11: CA23]
  Cardiomyopathy [ICD-11: BC43]
  Chronic obstructive pulmonary disease [ICD-11: CA22]
  Osteoarthritis [ICD-11: FA00-FA05]
  Pain [ICD-11: MG30-MG3Z]
  Psoriasis [ICD-11: EA90]
  Rheumatoid arthritis [ICD-11: FA20]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• BioChemical Class: Kinase
• UniProt ID: NOUNIPROTAC
• TTD ID: T34624

Molecular Interaction Atlas (MIA) of This DTT

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ARRY-797	DMJ48AB	Dilated cardiomyopathy	BC43.0	Phase 2	[2]
AZD7624	DMEW3K9	Chronic obstructive pulmonary disease	CA22	Phase 2	[1]
BMS-582949	DMGYXFP	Atherosclerosis	BD40	Phase 2	[3]
GSK2269557	DMIN0SV	Asthma	CA23	Phase 2	[4]
TAK-715	DMZKPI8	Rheumatoid arthritis	FA20	Phase 2	[5]
LY-2228820	DMHXTNW	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[6]

6 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ARRY-614	DMXD93K	Arthritis	FA20	Discontinued in Phase 1	[7]
AVE-9940	DMIB3AT	Rheumatoid arthritis	FA20	Discontinued in Phase 1	[8]
AZD-6703	DM9KLD3	Rheumatoid arthritis	FA20	Discontinued in Phase 1	[9]
SB-281832	DMYTAJW	Asthma	CA23	Discontinued in Phase 1	[10]
TA-5493	DMFES2K	Inflammation	1A00-CA43.1	Discontinued in Phase 1	[11]
AMG-548	DMYIPLH	Inflammation	1A00-CA43.1	Terminated	[12]

References

• [1] Investigational p38 inhibitors for the treatment of chronic obstructive pulmonary disease. Expert Opin Investig Drugs. 2015 Mar;24(3):383-92.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] 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.
• [4] Evaluation of WO2012032067 and WO2012055846: two selective PI3Kdelta inhibitors, which is GSK-2269557. Expert Opin Ther Pat. 2012 Aug;22(8):965-70.
• [5] 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.
• [6] 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).
• [7] Cmpany report (Arraybiopharma)
• [8] US patent application no. 2008,0119,498, Therapeutic agent for pruritus comprising p38 map kinase inhibitor as the active ingredient.
• [9] 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.
• [10] 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.
• [11] US patent application no. 2008,0269,123, Methods for treating polycystic kidney disease (pkd) or other cyst forming diseases.
• [12] p38 MAP kinase inhibitors: many are made, but few are chosen. Curr Opin Drug Discov Devel. 2005 Jul;8(4):421-30.