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

General Information of DTT (ID: TTQBR95)

• DTT Name: Stress-activated protein kinase 2a (p38 alpha) DTT Info
• UniProt ID: MK14_HUMAN
• Gene Name: MAPK14

Molecule-Related Drug & Molecule List

1 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ozagrel	DMIGKA1	Xerophthalmia	5B55.Y	Phase 4	[1]

4 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Losmapimod	DMIL37Z	Acute coronary syndrome	BA41	Phase 3	[1]
VX-702	DMKJDR6	Coronary artery disease	BA80	Phase 2a	[2], [3]
Dilmapimod	DMBYJ92	Acute lung injury	NB32.3	Phase 2	[1]
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[4], [5], [6]

6 Patented Agent(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[7]
PMID25991433-Compound-F2	DM37VIQ	N. A.	N. A.	Patented	[7]
PMID25991433-Compound-L1	DM2135Y	N. A.	N. A.	Patented	[7]
PMID25991433-Compound-L2	DM58UO9	N. A.	N. A.	Patented	[7]
PMID25991433-Compound-L3	DM3LWUR	N. A.	N. A.	Patented	[7]
PMID25991433-Compound-O2	DMTROIQ	N. A.	N. A.	Patented	[7]

8 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PAMAPIMOD	DM9SYUT	Rheumatoid arthritis	FA20	Discontinued in Phase 2	[8]
FR167653	DM69OR8	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 1	[9], [10]
R-1487	DM7WPI0	Rheumatoid arthritis	FA20	Discontinued in Phase 1	[11]
SB 235699	DMNH8XU	Psoriasis vulgaris	EA90	Discontinued in Phase 1	[4], [12]
SB-242235	DMKSFL0	Arthritis	FA20	Discontinued in Phase 1	[13]
SB 203580	DMAET6F	N. A.	N. A.	Terminated	[14], [15]
SB220025	DMSBUET	Arthritis	FA20	Terminated	[16]
SC-102	DM1MQ6Z	Solid tumour/cancer	2A00-2F9Z	Terminated	[17]

56 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(5-amino-1-phenyl-1H-pyrazol-4-yl)phenylmethanone	DMF0YJ3	Discovery agent	N.A.	Investigative	[18]
2-Chlorophenol	DM2E3X5	Discovery agent	N.A.	Investigative	[16]
3-(1-NAPHTHYLMETHOXY)PYRIDIN-2-AMINE	DMXMBEF	Discovery agent	N.A.	Investigative	[17]
3-(Benzyloxy)Pyridin-2-Amine	DM35VEI	Discovery agent	N.A.	Investigative	[16]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[19]
4-(2-Ethyl-4-m-tolyl-thiazol-5-yl)-pyridine	DMFJW2E	Discovery agent	N.A.	Investigative	[20]
4-PHENOXY-N-(PYRIDIN-2-YLMETHYL)BENZAMIDE	DMIPQTW	Discovery agent	N.A.	Investigative	[17]
4-Phenylsulfanyl-7H-pyrrolo[2,3-d]pyrimidine	DMHANXD	Discovery agent	N.A.	Investigative	[21]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	DMSKJ1X	Discovery agent	N.A.	Investigative	[22]
6-(4-Fluoro-phenylsulfanyl)-9H-purine	DM5JWEY	Discovery agent	N.A.	Investigative	[21]
6-Benzylsulfanyl-9H-purine	DMI7FNZ	Discovery agent	N.A.	Investigative	[21]
6-o-tolylquinazolin-2-amine	DM4TX9O	Discovery agent	N.A.	Investigative	[23]
6-Phenylsulfanyl-9H-purine	DMZ76NQ	Discovery agent	N.A.	Investigative	[21]
9-(4-Fluoro-benzyl)-6-phenylsulfanyl-9H-purine	DMW2NY9	Discovery agent	N.A.	Investigative	[21]
9-Benzyl-6-(4-fluoro-phenylsulfanyl)-9H-purine	DM8Q0D9	Discovery agent	N.A.	Investigative	[21]
9-Benzyl-6-phenylsulfanyl-9H-purine	DMNCL5G	Discovery agent	N.A.	Investigative	[21]
B-Octylglucoside	DMMO75G	Discovery agent	N.A.	Investigative	[16]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[24]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[24]
Dihydro-quinolinone	DM9UK6D	Discovery agent	N.A.	Investigative	[25]
DP-802	DMARTC2	Inflammation	1A00-CA43.1	Investigative	[26]
GSK-280	DM325YR	Inflammation	1A00-CA43.1	Investigative	[26]
GW-788388	DMIBUW5	Solid tumour/cancer	2A00-2F9Z	Investigative	[27]
IN-1130	DM3YJXF	Discovery agent	N.A.	Investigative	[28]
IN-1166	DMMS6D3	Discovery agent	N.A.	Investigative	[28]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[24]
KT-5720	DM9J50F	Discovery agent	N.A.	Investigative	[24]
L-779450	DM51B74	Discovery agent	N.A.	Investigative	[29]
ML-3163	DM3S5UC	Discovery agent	N.A.	Investigative	[30]
ML-3375	DMXJY6W	Discovery agent	N.A.	Investigative	[31]
ML-3403	DMTQWI8	Discovery agent	N.A.	Investigative	[31]
N-(3-(trifluoromethoxy)benzyl)-4-phenoxybenzamide	DM6UC8Y	Discovery agent	N.A.	Investigative	[32]
N-(3-(trifluoromethyl)benzyl)-4-phenoxybenzamide	DMSMRF9	Discovery agent	N.A.	Investigative	[32]
N-(4-(trifluoromethyl)benzyl)-4-phenoxybenzamide	DMZ0V8O	Discovery agent	N.A.	Investigative	[32]
N-(4-fluorobenzyl)-N-(pyridin-4-yl)-2-naphthamide	DMP1ICB	Discovery agent	N.A.	Investigative	[33]
N-(4-methyl-benzyl)-4-phenoxy-benzamide	DMZX2BH	Discovery agent	N.A.	Investigative	[32]
Oxindole 94	DMPFD6Y	Pain	MG30-MG3Z	Investigative	[34]
PD-0166326	DMD2CG9	Discovery agent	N.A.	Investigative	[35]
PD-0173956	DM8RW92	Discovery agent	N.A.	Investigative	[35]
PHA-666859	DMHQ6KT	Diabetic retinopathy	9B71.0	Investigative	[26]
Phenyl-(3-phenyl-1H-indazol-6-yl)-amine	DMDCTNU	Discovery agent	N.A.	Investigative	[36]
PMID22521646C12	DMYQDXO	Discovery agent	N.A.	Investigative	[37]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[24]
Ro-3201195	DM9GXYV	Discovery agent	N.A.	Investigative	[38]
Ro31-8220	DMDJLF0	Discovery agent	N.A.	Investigative	[24]
RWJ-68354	DMNLVRS	Discovery agent	N.A.	Investigative	[39]
SB-216995	DMOH9TA	Discovery agent	N.A.	Investigative	[25]
SB-218655	DMJKE4M	Discovery agent	N.A.	Investigative	[25]
SB-227931	DMO1WI8	Discovery agent	N.A.	Investigative	[40]
Small molecule 34	DMWJ70Q	Discovery agent	N.A.	Investigative	[16]
STAUROSPORINONE	DMU2H4K	Discovery agent	N.A.	Investigative	[24]
Talmapimod	DMMTSL2	Discovery agent	N.A.	Investigative	[41], [42]
Triazolopyridine	DM1F2K0	Discovery agent	N.A.	Investigative	[17]
Tyrphostin Ag-1478	DM87ZIH	Discovery agent	N.A.	Investigative	[43]
UCB-1277763	DMFUE43	Inflammation	1A00-CA43.1	Investigative	[26]
ZM-336372	DMD5JYQ	Discovery agent	N.A.	Investigative	[44]

References

• [1] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [2] Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum. 2009 May;60(5):1232-41.
• [3] Comparative renal excretion of VX-702, a novel p38 MAPK inhibitor, and methotrexate in the perfused rat kidney model. Drug Dev Ind Pharm. 2010 Mar;36(3):315-22.
• [4] Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [8] Selective p38alpha inhibitors clinically evaluated for the treatment of chronic inflammatory disorders. J Med Chem. 2010 Mar 25;53(6):2345-53.
• [9] Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653. Arthritis Rheum. 2003 Sep;48(9):2670-81.
• [10] Involvement of p38 mitogen-activated protein kinase followed by chemokine expression in crescentic glomerulonephritis. Am J Kidney Dis. 2001 Dec;38(6):1169-77.
• [11] Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38alpha mitogen-activated protein kinase. J Med Chem. 2011 Apr 14;54(7):2255-65.
• [12] 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.
• [13] Biphenyl amide p38 kinase inhibitors 4: DFG-in and DFG-out binding modes. Bioorg Med Chem Lett. 2008 Aug 1;18(15):4433-7.
• [14] The p38 mitogen-activated protein kinase pathway plays a critical role in thrombin-induced endothelial chemokine production and leukocyte recruitment. Blood. 2001 Aug 1;98(3):667-73.
• [15] Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19.
• [16] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [17] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [18] Discovery of S-[5-amino-1-(4-fluorophenyl)-1H-pyrazol-4-yl]-[3-(2,3-dihydroxypropoxy)phenyl]methanone (RO3201195), an orally bioavailable and highl... J Med Chem. 2006 Mar 9;49(5):1562-75.
• [19] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [20] Novel inhibitor of p38 MAP kinase as an anti-TNF-alpha drug: discovery of N-[4-[2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]-2-pyridyl]benzamide (T... J Med Chem. 2005 Sep 22;48(19):5966-79.
• [21] Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors. J Med Chem. 2005 Feb 10;48(3):710-22.
• [22] 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9.
• [23] Discovery of aminoquinazolines as potent, orally bioavailable inhibitors of Lck: synthesis, SAR, and in vivo anti-inflammatory activity. J Med Chem. 2006 Sep 21;49(19):5671-86.
• [24] Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
• [25] In silico search for multi-target anti-inflammatories in Chinese herbs and formulas. Bioorg Med Chem. 2010 Mar 15;18(6):2204-2218.
• [26] 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: 1499).
• [27] Discovery of 4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388): a potent, selective, and orall... J Med Chem. 2006 Apr 6;49(7):2210-21.
• [28] Synthesis and biological evaluation of trisubstituted imidazole derivatives as inhibitors of p38alpha mitogen-activated protein kinase. Bioorg Med Chem Lett. 2008 Jul 15;18(14):4006-10.
• [29] The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2006 Jan 15;16(2):378-81.
• [30] From imidazoles to pyrimidines: new inhibitors of cytokine release. J Med Chem. 2002 Jun 20;45(13):2733-40.
• [31] Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes. J Med Chem. 2003 Jul 17;46(15):3230-44.
• [32] Two classes of p38alpha MAP kinase inhibitors having a common diphenylether core but exhibiting divergent binding modes. Bioorg Med Chem Lett. 2005 Dec 1;15(23):5274-9.
• [33] Amide-based inhibitors of p38alpha MAP kinase. Part 2: design, synthesis and SAR of potent N-pyrimidyl amides. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2560-3.
• [34] Inhibition of p38 MAPK decreases myocardial TNF-alpha expression and improves myocardial function and survival in endotoxemia. Cardiovasc Res. 2003 Oct 1;59(4):893-900.
• [35] Structure-activity relationships of 6-(2,6-dichlorophenyl)-8-methyl-2-(phenylamino)pyrido[2,3-d]pyrimidin-7-ones: toward selective Abl inhibitors. Bioorg Med Chem Lett. 2009 Dec 15;19(24):6872-6.
• [36] Design and synthesis of 6-anilinoindazoles as selective inhibitors of c-Jun N-terminal kinase-3. Bioorg Med Chem Lett. 2005 Nov 15;15(22):5095-9.
• [37] Novel triazolopyridylbenzamides as potent and selective p38alpha inhibitors. Bioorg Med Chem Lett. 2012 May 15;22(10):3431-6.
• [38] Microwave-assisted synthesis of 5-aminopyrazol-4-yl ketones and the p38(MAPK) inhibitor RO3201195 for study in Werner syndrome cells. Bioorg Med Chem Lett. 2008 Jul 1;18(13):3745-8.
• [39] Imidazopyrimidines, potent inhibitors of p38 MAP kinase. Bioorg Med Chem Lett. 2003 Feb 10;13(3):347-50.
• [40] The neuroprotective action of JNK3 inhibitors based on the 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole scaffold. Bioorg Med Chem Lett. 2005 Nov 1;15(21):4666-70.
• [41] Mitogen-activated protein kinases in innate immunity.Nat Rev Immunol.2013 Sep;13(9):679-92.
• [42] p38 MAP Kinase Inhibition Reduces Propionibacterium acnes-Induced Inflammation in Vitro. Dermatol Ther (Heidelb). 2015 Mar;5(1):53-66.
• [43] Novel, potent and selective anilinoquinazoline and anilinopyrimidine inhibitors of p38 MAP kinase. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5389-94.
• [44] A novel series of p38 MAP kinase inhibitors for the potential treatment of rheumatoid arthritis. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5383-7.