Details of the Drug

General Information of Drug (ID: DMDG8Q3)

Drug Name

Varlitinib

Synonyms

VARLITINIB; 845272-21-1; ARRY-334543; ARRY334543; ARRY 334543; ARRY-543; UNII-846Y8197W1; ASLAN-001; 846Y8197W1; (R)-N4-(3-chloro-4-(thiazol-2-ylmethoxy)phenyl)-N6-(4-methyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine; Varlitinib [USAN:INN]; Varlitinib (ARRY334543); Varlitinib free base; Varlitinib (USAN/INN); MLS006011274; GTPL7645; SCHEMBL1384578; CHEMBL2103842; SYN1192; MolPort-028-720-424; EX-A1005; 4-N-[3-chloro-4-(1,3-thiazol-2-ylmethoxy)phenyl]-6-N-[(4R)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]quinazoline-4,6-diamine

Indication

Disease Entry	ICD 11	Status	REF
Metastatic biliary tract neoplasms	2C14-2C17	Phase 2/3	[1]
Breast cancer	2C60-2C65	Phase 1/2	[2], [3]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

466.9

Topological Polar Surface Area (xlogp)

4.2

Rotatable Bond Count (rotbonds)

7

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

8

Chemical Identifiers

Formula: C22H19ClN6O2S
IUPAC Name: 4-N-[3-chloro-4-(1,3-thiazol-2-ylmethoxy)phenyl]-6-N-[(4R)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]quinazoline-4,6-diamine
Canonical SMILES: C[C@@H]1COC(=N1)NC2=CC3=C(C=C2)N=CN=C3NC4=CC(=C(C=C4)OCC5=NC=CS5)Cl
InChI: InChI=1S/C22H19ClN6O2S/c1-13-10-31-22(27-13)29-14-2-4-18-16(8-14)21(26-12-25-18)28-15-3-5-19(17(23)9-15)30-11-20-24-6-7-32-20/h2-9,12-13H,10-11H2,1H3,(H,27,29)(H,25,26,28)/t13-/m1/s1
InChIKey: UWXSAYUXVSFDBQ-CYBMUJFWSA-N

Cross-matching ID

PubChem CID: 42642648
CAS Number: 845272-21-1
DrugBank ID: DB05944
TTD ID: D00NYJ

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	Modulator	[4]
Erbb2 tyrosine kinase receptor (HER2)	TT6EO5L	ERBB2_HUMAN	Modulator	[4]

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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

Metastatic biliary tract neoplasms

ICD Disease Classification

2C14-2C17

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Epidermal growth factor receptor (EGFR)	DTT	EGFR	8.30E-26	0.06	0.13

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	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: 7645).
3	ClinicalTrials.gov (NCT00862524) A Study of ARRY-334543 and Gemcitabine in Patients With Advanced Cancer and Pancreatic Cancer. U.S. National Institutes of Health.
4	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
5	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.
6	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: 7422).
7	Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
8	Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
9	2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
10	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
11	Her2/neu is not a commonly expressed therapeutic target in melanoma -- a large cohort tissue microarray study. Melanoma Res. 2004 Jun;14(3):207-10.
12	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
13	Clinical pipeline report, company report or official report of Roche (2009).
14	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
15	Nasopharyngeal carcinoma: Current treatment options and future directions. J Nasopharyng Carcinoma, 2014, 1(16): e16.
16	Gefitinib ('Iressa', ZD1839) and new epidermal growth factor receptor inhibitors. Br J Cancer. 2004 Feb 9;90(3):566-72.
17	Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
18	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.
19	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).
20	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.