Details of the Drug

General Information of Drug (ID: DMEFW3G)

Drug Name

KD019

Synonyms

Tesevatinib; XL647; XL-647; 781613-23-8; EXEL-7647; UNII-F6XM2TN5A1; KD-019; XL 647; F6XM2TN5A1; 651031-01-5; 7-[[(3aS,6aR)-2-methyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]methoxy]-N-(3,4-dichloro-2-fluorophenyl)-6-methoxyquinazolin-4-amine; Tesevatinib [USAN:INN]; EXEL 7647; 874286-84-7; KD 019; 1000599-06-3; SCHEMBL721994; SCHEMBL721993; SCHEMBL721992; C24H25Cl2FN4O2; GTPL7944; CHEMBL3544983; EX-A172; QCR-153; MolPort-044-724-458; BCP23438; ZINC38912363; 2809AH; AKOS027255007

Indication

Disease Entry	ICD 11	Status	REF
Brain metastases	2D50	Phase 2	[1]
Meningioma metastases	2D51	Phase 2	[1]
Non-small-cell lung cancer	2C25.Y	Phase 2	[2]
Polycystic kidney disease	GB8Y	Phase 2	[3], [4]
Recurrent glioblastoma	2A00.00	Phase 2	[1], [5]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

491.4

Topological Polar Surface Area (xlogp)

5.8

Rotatable Bond Count (rotbonds)

6

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

7

ADMET Property

Half-life: The concentration or amount of drug in body reduced by one-half in 50 - 70 hours [6]

Chemical Identifiers

Formula: C24H25Cl2FN4O2
IUPAC Name: 7-[[(3aS,6aR)-2-methyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]methoxy]-N-(3,4-dichloro-2-fluorophenyl)-6-methoxyquinazolin-4-amine
Canonical SMILES: CN1C[C@H]2CC(C[C@H]2C1)COC3=C(C=C4C(=C3)N=CN=C4NC5=C(C(=C(C=C5)Cl)Cl)F)OC
InChI: InChI=1S/C24H25Cl2FN4O2/c1-31-9-14-5-13(6-15(14)10-31)11-33-21-8-19-16(7-20(21)32-2)24(29-12-28-19)30-18-4-3-17(25)22(26)23(18)27/h3-4,7-8,12-15H,5-6,9-11H2,1-2H3,(H,28,29,30)/t13?,14-,15+
InChIKey: HVXKQKFEHMGHSL-GOOCMWNKSA-N

Cross-matching ID

PubChem CID: 10458325
CAS Number: 781613-23-8
DrugBank ID: DB11973
TTD ID: D06WRF

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Ephrin type-B receptor 4 (EPHB4)	TTI4ZX2	EPHB4_HUMAN	Modulator	[7], [8]
Tyrosine-protein kinase (PTK)	TTJSQEF	NOUNIPROTAC	Inhibitor	[1], [5]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Brain metastases

ICD Disease Classification

2D50

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Ephrin type-B receptor 4 (EPHB4)	DTT	EPHB4	4.05E-01	6.00E-03	0.02

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2	ClinicalTrials.gov (NCT01487174) KD019 Versus Erlotinib in Subjects With Stage IIIB/IV Non Small Cell Lung Cancer With Progression After First- or Second-Line Chemotherapy. U.S. National Institutes of Health.
3	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: 7944).
4	ClinicalTrials.gov (NCT00364780) Study of XL647 in Subjects With Non-Small-Cell Lung Cancer. U.S. National Institutes of Health.
5	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
7	XL647--a multitargeted tyrosine kinase inhibitor: results of a phase II study in subjects with non-small cell lung cancer who have progressed after responding to treatment with either gefitinib or erlotinib. J Thorac Oncol. 2012 Jan;7(1):219-26.
8	Phase II study of the multitargeted tyrosine kinase inhibitor XL647 in patients with non-small-cell lung cancer. J Thorac Oncol. 2012 May;7(5):856-65.
9	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
10	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
11	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
12	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.
13	Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem. 2013 Apr 11;56(7):2936-47.
14	Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). J Med Chem. 2009 Oct 22;52(20):6433-46.
15	Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinas... Bioorg Med Chem Lett. 2007 Feb 1;17(3):602-8.
16	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: 1833).