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

General Information of Drug (ID: DMTIA27)

• Drug Name: 4-[3-Hydroxyanilino]-6,7-Dimethoxyquinazoline Drug Info
• Synonyms: 4-[3-Hydroxyanilino]-6,7-dimethoxyquinazoline; whi-p180; 211555-08-7; 3-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol; WHI-P180, Hydrochloride; JANEX 3; 4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE; CHEMBL127907; 3-((6,7-Dimethoxyquinazolin-4-yl)amino)phenol; AK341047; DTQ; 4-(3& -Hydroxyphenyl)amino-6,7-dimethoxyquinazoline, HCl; JANEX-3; 4btk; 1di8; AC1L1KWT; AC1Q4XVE; 3-(6,7-dimethoxyquinazolin-4-ylamino)phenol; Anilinoquinazoline deriv 5; WHI-P180(Janex 3); BDBM4622; SCHEMBL1180103; CTK4E5981; AOB5495; MolPort-000-672-017; BNDYIYYKEIXHNK-UHFFFAOYSA-N; HMS3229P15; WHI-P180

Indication

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

• Cross-matching ID:
  PubChem CID: 5687
  TTD Drug ID: DMTIA27

Molecule-Related Drug Atlas

Drug(s) Targeting Cyclin-dependent kinase 2 (CDK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
R-roscovitine	DMSH108	Non-small-cell lung cancer	2C25.Y	Phase 2	[3]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]
PHA848125	DMS2Q9G	Thymic cancer	2C27	Phase 2	[5]
TG02	DMZFIGQ	Anaplastic astrocytoma	2A00.0	Phase 1/2	[6]
NUV-422	DMQJQNT	Malignant glioma	2A00.0	Phase 1/2	[7]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[8]
FN-1501	DM7BMD6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]

Drug(s) Targeting Vascular endothelial growth factor receptor 2 (KDR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[12]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[13]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[14]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[15]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[16]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[17]
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[18]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[19]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[1]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[2]

References

• [1] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [2] Pharmacophore modeling and in silico screening for new KDR kinase inhibitors. Bioorg Med Chem Lett. 2007 Apr 15;17(8):2126-33.
• [3] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [4] 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.
• [5] Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J Med Chem. 2009 Aug 27;52(16):5152-63.
• [6] Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
• [7] ClinicalTrials.gov (NCT04541225) Phase 1/2 Dose Escalation, Safety, Pharmacokinetics, and Efficacy Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors. U.S.National Institutes of Health.
• [8] Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia. 2013 Dec;27(12):2366-75.
• [9] Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia. J Med Chem. 2018 Feb 22;61(4):1499-1518.
• [10] A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-dependent kinases (CDK2, 1 and 4) reveals unexpected h... Cell Cycle. 2011 Mar 15;10(6):963-70.
• [11] Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.
• [12] 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.
• [13] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [15] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [16] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [17] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [18] Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014;15(12):1635-45.
• [19] Clinical pipeline report, company report or official report of Exelixis (2011).
• [20] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services