General Information of Drug (ID: DMY0UEQ)

Drug Name
VATALANIB
Synonyms
Vatalanib; 212141-54-3; Vatalanib base; N-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine; PTK787; Pynasunate; CGP 79787; Vatalanib free base; PTK-787; Vatalanib (free base); Vatalinib; ZK-232934; CGP-79787; ZK222584; PTK/ZK; CHEMBL101253; N-(4-Chlorophenyl)-4-(4-pyridinylmethyl)-1-phthalazinamine; UNII-5DX9U76296; CHEBI:90620; YCOYDOIWSSHVCK-UHFFFAOYSA-N; 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine; 5DX9U76296; NCGC00181350-01; 1-Phthalazinamine,N-(4-chlorophenyl)-4-(4-pyridinylmethyl)-; DSSTox_CID_26919
Indication
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 2 [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 346.8
Topological Polar Surface Area (xlogp) 4.5
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 4
ADMET Property
Absorption
The drug is rapidly absorbed [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 6 hours [4]
Chemical Identifiers
Formula
C20H15ClN4
IUPAC Name
N-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine
Canonical SMILES
C1=CC=C2C(=C1)C(=NN=C2NC3=CC=C(C=C3)Cl)CC4=CC=NC=C4
InChI
InChI=1S/C20H15ClN4/c21-15-5-7-16(8-6-15)23-20-18-4-2-1-3-17(18)19(24-25-20)13-14-9-11-22-12-10-14/h1-12H,13H2,(H,23,25)
InChIKey
YCOYDOIWSSHVCK-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
151194
ChEBI ID
CHEBI:90620
CAS Number
212141-54-3
DrugBank ID
DB04879
TTD ID
D0P6DJ

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [5]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Inhibitor [5]
Vascular endothelial growth factor receptor 3 (FLT-4) TTDCBX5 VGFR3_HUMAN Inhibitor [6]
VEGFR1 messenger RNA (VEGFR1 mRNA) TT1VAUK VGFR1_HUMAN Inhibitor [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Solid tumour/cancer
ICD Disease Classification 2A00-2F9Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Vascular endothelial growth factor receptor 2 (KDR) DTT KDR 1.98E-01 0.11 0.2
Vascular endothelial growth factor receptor 3 (FLT-4) DTT FLT4 6.00E-01 -0.04 -0.23
VEGFR1 messenger RNA (VEGFR1 mRNA) DTT FLT1 1.64E-05 0.29 0.51
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

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: 5705).
2 ClinicalTrials.gov (NCT00348790) Vatalanib in Treating Patients With Recurrent or Progressive Meningioma. U.S. National Institutes of Health.
3 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 Dual irreversible kinase inhibitors: quinazoline-based inhibitors incorporating two independent reactive centers with each targeting different cyst... Bioorg Med Chem. 2007 Jun 1;15(11):3635-48.
6 Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors. J Med Chem. 2005 Mar 10;48(5):1610-9.
7 Inhibitors of VEGF receptors-1 and -2 based on the 2-((pyridin-4-yl)ethyl)pyridine template. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1913-9.
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
9 E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405.
10 Clinical pipeline report, company report or official report of Hutchison Medi Pharma.
11 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.
12 Company report (Medigen)
13 Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
14 Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther. 2006 Apr;5(4):995-1006.
15 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: 1814).
16 Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
17 MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
18 Nasopharyngeal carcinoma: Current treatment options and future directions. J Nasopharyng Carcinoma, 2014, 1(16): e16.
19 Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009 Mar;153(1):13-7.
20 Gefitinib ('Iressa', ZD1839) and new epidermal growth factor receptor inhibitors. Br J Cancer. 2004 Feb 9;90(3):566-72.
21 Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
22 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.
23 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: 1797).
24 Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
25 Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
26 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
27 New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven a... J Med Chem. 2000 Jun 15;43(12):2310-23.
28 2011 Pipeline of Sirna Therapeutics.
29 The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2012 Aug 1;22(15):4979-85.
30 Design and structure-activity relationship of 3-benzimidazol-2-yl-1H-indazoles as inhibitors of receptor tyrosine kinases. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3595-9.
31 Macrocyclic ureas as potent and selective Chk1 inhibitors: an improved synthesis, kinome profiling, structure-activity relationships, and prelimina... Bioorg Med Chem Lett. 2007 Dec 1;17(23):6593-601.
32 Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents. J Med Chem. 2004 Oct 21;47(22):5367-80.
33 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.
34 Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
35 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
36 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
37 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
38 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
39 Clinical pipeline report, company report or official report of Exelixis (2011).
40 Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.