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

General Information of Drug (ID: DM4TX9O)

• Drug Name: 6-o-tolylquinazolin-2-amine Drug Info
• Synonyms: 6-o-tolylquinazolin-2-amine; CHEMBL215952; SCHEMBL5494575; RAWAQXBVMDKSIO-UHFFFAOYSA-N; ZINC35049815

Indication

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

• Cross-matching ID:
  PubChem CID: 16086113
  TTD Drug ID: DM4TX9O

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Chronic myelogenous leukaemia	2A20.0	Approved	[2]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]
JNJ-26483327	DMSQ3AZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[4]
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 Janus kinase 3 (JAK-3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tofacitinib	DMBS370	Rheumatoid arthritis	FA20	Approved	[9]
Asp-015K	DMZ1UOI	Psoriasis vulgaris	EA90	Phase 3	[10]
PF-06651600	DMYKNME	Alopecia	ED70	Phase 2/3	[11]
VX-509	DM2U3MX	Rheumatoid arthritis	FA20	Phase 2/3	[12]
Cerdulatinib	DMSCR2H	B-cell lymphoma	2A86	Phase 2	[11]
ATI-501	DMTY6OF	Alopecia	ED70	Phase 2	[13]
ATI-502	DM8NODR	Alopecia	ED70	Phase 2	[14]
SNA-125	DM8L1GJ	Atopic dermatitis	EA80	Phase 1	[11]
Pyrazolo[4,3-c]pyridine derivative 2	DMCDFLQ	N. A.	N. A.	Patented	[15]
PMID27774824-Compound-Figure9Example2down	DMXAV42	N. A.	N. A.	Patented	[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 Vascular endothelial growth factor receptor 2 (KDR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Hepatocellular carcinoma	2C12.02	Approved	[20]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[21]
Regorafenib	DMHSY1I	Metastatic colorectal cancer	2B91	Approved	[9]
Sunitinib	DMCBJSR	Gastrointestinal cancer	2C11	Approved	[22]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[23]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[2]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[24]
Cabozantinib	DMIYDT4	Thyroid cancer	2D10	Approved	[25]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[26]
Lenvatinib	DMB1IU4	Thyroid cancer	2D10	Approved	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Janus kinase 3 (JAK-3)	TTT7PJU	JAK3_HUMAN	Inhibitor	[1]
LCK tyrosine protein kinase (LCK)	TT860QF	LCK_HUMAN	Inhibitor	[1]
Stress-activated protein kinase 2a (p38 alpha)	TTQBR95	MK14_HUMAN	Inhibitor	[1]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[1]

References

• [1] 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.
• [2] 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.
• [3] National Cancer Institute Drug Dictionary (drug id 596693).
• [4] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [10] 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: 2049).
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] Selective JAK inhibitors in development for rheumatoid arthritis. Expert Opin Investig Drugs. 2014 Aug;23(8):1067-77.
• [13] Clinical pipeline report, company report or official report of Aclaris Therapeutics.
• [14] ClinicalTrials.gov (NCT03759340) ATI-502 Topical Solution for the Treatment of Alopecia Areata (AA), Alopecia Universalis (AU) and Alopecia Totalis (AT). U.S. National Institutes of Health.
• [15] Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1.Expert Opin Ther Pat. 2017 Feb;27(2):127-143.
• [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] Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
• [21] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [22] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [23] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [24] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [25] Clinical pipeline report, company report or official report of Exelixis (2011).
• [26] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [27] Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.