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

General Information of Drug (ID: DMTQWI8)

• Drug Name: ML-3403 Drug Info
• Synonyms: p38 MAP Kinase Inhibitor III; ML3403; 549505-65-9; ML 3403; 4-(4-(4-fluorophenyl)-2-(methylthio)-1H-imidazol-5-yl)-N-(1-phenylethyl)pyridin-2-amine; CHEMBL111364; (RS)-{4-[5-(4-Fluorophenyl)-2-methylsulfanyl-3H-imidazol-4-yl]pyridin-2-yl}-(1-phenylethyl)amine]; K00568a; AC1O4WCF; SCHEMBL2896072; GTPL6014; ml-3043; SCHEMBL15013352; MolPort-023-278-904; HMS3229M04; {4-[5-(4-Fluoro-phenyl)-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 6419739
  CAS Number: CAS 549505-65-9
  TTD Drug ID: DMTQWI8

Molecule-Related Drug Atlas

Drug(s) Targeting Albendazole monooxygenase (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[3]
PMX-53	DMZUAJ4	Atopic dermatitis	EA80	Phase 2	[4]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[5]
Heme	DMGC287	Discovery agent	N.A.	Investigative	[6]
ML-3163	DM3S5UC	Discovery agent	N.A.	Investigative	[2]
6-(3-Hydroxy-phenyl)-naphthalen-2-ol	DMH8WA2	Discovery agent	N.A.	Investigative	[7]
2-(2-(4-tert-Butylphenylthio)ethyl)-1H-imidazole	DMZVBPG	Discovery agent	N.A.	Investigative	[8]
ML-3375	DMXJY6W	Discovery agent	N.A.	Investigative	[2]
4-[5-(3-Hydroxyphenyl)-3-thienyl]-2-methylphenol	DM7ERYJ	Discovery agent	N.A.	Investigative	[9]
2-Fluoro-4-[5-(3-hydroxyphenyl)-2-thienyl]phenol	DMUGAT8	Discovery agent	N.A.	Investigative	[9]

Drug(s) Targeting Stress-activated protein kinase 2b (p38 beta)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[10]
SB 235699	DMNH8XU	Psoriasis vulgaris	EA90	Discontinued in Phase 1	[10]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[11]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[11]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[12]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[11]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[11]
Ro31-8220	DMDJLF0	Discovery agent	N.A.	Investigative	[11]
STAUROSPORINONE	DMU2H4K	Discovery agent	N.A.	Investigative	[11]
KT-5720	DM9J50F	Discovery agent	N.A.	Investigative	[11]

Drug(s) Targeting Stress-activated protein kinase 2a (p38 alpha)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ozagrel	DMIGKA1	Xerophthalmia	5B55.Y	Phase 4	[13]
Losmapimod	DMIL37Z	Acute coronary syndrome	BA41	Phase 3	[13]
VX-702	DMKJDR6	Coronary artery disease	BA80	Phase 2a	[14]
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[10]
Dilmapimod	DMBYJ92	Acute lung injury	NB32.3	Phase 2	[13]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-F2	DM37VIQ	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-L2	DM58UO9	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-L3	DM3LWUR	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-L1	DM2135Y	N. A.	N. A.	Patented	[15]

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)	[16]
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[17]
ARRY-797	DMJ48AB	Dilated cardiomyopathy	BC43.0	Phase 2	[18]
KC706	DMBX6C7	Cardiovascular disease	BA00-BE2Z	Discontinued in Phase 2	[19]
SB 235699	DMNH8XU	Psoriasis vulgaris	EA90	Discontinued in Phase 1	[20]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[11]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[11]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[12]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[11]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[6]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Albendazole monooxygenase (CYP3A4)	TTXV4FI	CP3A4_HUMAN	Inhibitor	[2]
MAP kinase p38 (MAPK12)	TTYT93M	MK12_HUMAN	Inhibitor	[2]
Stress-activated protein kinase 2a (p38 alpha)	TTQBR95	MK14_HUMAN	Inhibitor	[2]
Stress-activated protein kinase 2b (p38 beta)	TT73U6C	MK11_HUMAN	Inhibitor	[2]

References

• [1] 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: 6014).
• [2] 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.
• [3] Structure-activity relationships for the inhibition of recombinant human cytochromes P450 by curcumin analogues. Eur J Med Chem. 2008 Aug;43(8):1621-31.
• [4] Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92.
• [5] Discovery and evaluation of 4-(2-(4-chloro-1H-pyrazol-1-yl)ethylamino)-3-(6-(1-(3-fluoropropyl)piperidin-4-yl)-4-methyl-1H-benzo[d]imidazol-2-yl)py... J Med Chem. 2008 Oct 9;51(19):5897-900.
• [6] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [7] Design, synthesis, and biological evaluation of (hydroxyphenyl)naphthalene and -quinoline derivatives: potent and selective nonsteroidal inhibitors... J Med Chem. 2008 Apr 10;51(7):2158-69.
• [8] Role of hydrophobic substituents on the terminal nitrogen of histamine in receptor binding and agonist activity: development of an orally active hi... J Med Chem. 2010 May 13;53(9):3840-4.
• [9] New insights into the SAR and binding modes of bis(hydroxyphenyl)thiophenes and -benzenes: influence of additional substituents on 17beta-hydroxyst... J Med Chem. 2009 Nov 12;52(21):6724-43.
• [10] Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
• [11] Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
• [12] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [13] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [14] 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.
• [15] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [16] Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63.
• [17] 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.
• [18] Array BioPharmas ARRY-797 Meets Primary Endpoint in Clinical Proof of Concept Trial in Osteoarthritis Patients Whose Pain is Poorly Controlled by NSAIDs
• [19] KC706, an Oral p38 MAP Kinase Inhibitor, Increases HDL-C. Circulation. 2007;116:II_126.
• [20] 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.