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

General Information of Drug (ID: DMD5JYQ)

• Drug Name: ZM-336372 Drug Info
• Synonyms: ZM 336372; 208260-29-1; ZM336372; ZM-336372; 3-(dimethylamino)-N-(3-(4-hydroxybenzamido)-4-methylphenyl)benzamide; N-[5-(3-Dimethylaminobenzamido)-2-methylphenyl]-4-hydroxybenzamide; CHEMBL186526; n-(5-(3-dimethylaminobenzamido)-2-methylphenyl)-4-hydroxybenzamide; 3-(dimethylamino)-N-{3-[(4-hydroxybenzoyl)amino]-4-methylphenyl}benzamide; 3-(dimethylamino)-N-[3-[(4-hydroxybenzoyl)amino]-4-methylphenyl]benzamide; 3-(dimethylamino)-N-[3-(4-hydroxybenzamido)-4-methylphenyl]benzamide; Bio1_001346; compound 1 [PMID: 15454231

Indication

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

• Cross-matching ID:
  PubChem CID: 5730
  ChEBI ID: CHEBI:95033
  CAS Number: CAS 208260-29-1
  TTD Drug ID: DMD5JYQ

Molecule-Related Drug Atlas

Drug(s) Targeting LCK tyrosine protein kinase (LCK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[3]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
JNJ-26483327	DMSQ3AZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[1]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[5]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[5]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[6]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[5]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[7]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[8]

Drug(s) Targeting Raf messenger RNA (Raf mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MLN2480	DMBR8NF	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
RG7304	DMGFAVQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
SPN-803	DM8O2AQ	Parkinson disease	8A00.0	Phase 1	[9]
LXH254	DMQE9PS	Non-small-cell lung cancer	2C25.Y	Phase 1	[11]
ICo-007	DM79W8K	Diabetic macular edema	9B71.02	Phase 1	[12]
LErafAON	DMNHPOT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]
DEBROMOHYMENIALDISINE	DMDLER8	Discovery agent	N.A.	Investigative	[14]
6-[(E)-2-(4-Fluoro-phenyl)-vinyl]-9H-purine	DMDNG8F	Discovery agent	N.A.	Investigative	[15]
PLX-ORI3	DMZG1L5	Solid tumour/cancer	2A00-2F9Z	Investigative	[9]
6-Benzylsulfanyl-9H-purine	DMI7FNZ	Discovery agent	N.A.	Investigative	[15]

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	[16]
Losmapimod	DMIL37Z	Acute coronary syndrome	BA41	Phase 3	[16]
VX-702	DMKJDR6	Coronary artery disease	BA80	Phase 2a	[17]
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[18]
Dilmapimod	DMBYJ92	Acute lung injury	NB32.3	Phase 2	[16]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[19]
PMID25991433-Compound-F2	DM37VIQ	N. A.	N. A.	Patented	[19]
PMID25991433-Compound-L2	DM58UO9	N. A.	N. A.	Patented	[19]
PMID25991433-Compound-L3	DM3LWUR	N. A.	N. A.	Patented	[19]
PMID25991433-Compound-L1	DM2135Y	N. A.	N. A.	Patented	[19]

Drug(s) Targeting B-Raf messenger RNA (BRAF mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MLN2480	DMBR8NF	Solid tumour/cancer	2A00-2F9Z	Phase 2	[20]
RG7304	DMGFAVQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
SPN-803	DM8O2AQ	Parkinson disease	8A00.0	Phase 1	[20]
PLX-4720	DMBK9AM	Cutaneous melanoma	2C30	Phase 1	[21]
L-779450	DM51B74	Discovery agent	N.A.	Investigative	[22]
PLX-ORI3	DMZG1L5	Solid tumour/cancer	2A00-2F9Z	Investigative	[20]
2-(Phenylamino)-6-(3-acetamidophenyl)pyrazine	DMPUARE	Discovery agent	N.A.	Investigative	[23]
ISIS 13741	DMC7Q38	Discovery agent	N.A.	Investigative	[24]
ISIS 14144	DMWIKD5	Discovery agent	N.A.	Investigative	[24]
PMID26061392C2	DMHZOIU	Discovery agent	N.A.	Investigative	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
B-Raf messenger RNA (BRAF mRNA)	TT0EOB8	BRAF_HUMAN	Inhibitor	[1]
LCK tyrosine protein kinase (LCK)	TT860QF	LCK_HUMAN	Inhibitor	[1]
Raf messenger RNA (Raf mRNA)	TTAN5W2	RAF1_HUMAN	Inhibitor	[1]
Stress-activated protein kinase 2a (p38 alpha)	TTQBR95	MK14_HUMAN	Inhibitor	[2]

References

• [1] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [2] 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.
• [3] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [4] National Cancer Institute Drug Dictionary (drug id 596693).
• [5] Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
• [6] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [7] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [8] Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitum... J Med Chem. 2005 Sep 8;48(18):5639-43.
• [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. (Target id: 2184).
• [10] Clinical pipeline report, company report or official report of Roche.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2009).
• [13] Combination with liposome-entrapped, ends-modified raf antisense oligonucleotide (LErafAON) improves the anti-tumor efficacies of cisplatin, epirubicin, mitoxantrone, docetaxel and gemcitabine. Anticancer Drugs. 2004 Mar;15(3):243-53.
• [14] Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1). J Med Chem. 2002 Jan 17;45(2):529-32.
• [15] Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors. J Med Chem. 2005 Feb 10;48(3):710-22.
• [16] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [17] 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.
• [18] Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
• [19] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [20] 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: 1943).
• [21] Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011 Oct 30;29(11):1046-51.
• [22] The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2006 Jan 15;16(2):378-81.
• [23] Novel inhibitors of B-RAF based on a disubstituted pyrazine scaffold. Generation of a nanomolar lead. J Med Chem. 2006 Jan 12;49(1):407-16.
• [24] US patent application no. 5,981,731, Antisense oligonucleotide modulation of B-raf gene expression.
• [25] Photoactivatable Prodrugs of Antimelanoma Agent Vemurafenib. ACS Chem Biol. 2015 Sep 18;10(9):2099-107.