Varlitinib - Moligand™, 10mM in DMSO , Receptor protein-tyrosine kinase erbB-2 inhibitor, CAS No.845272-21-1, Receptor protein-tyrosine kinase erbB-2 inhibitor

CAS: 845272-21-1 Cat. No.: V407853 Molecular Weight: 466.94 EC Number: 807-347-4 PubChem CID: 42642648

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

ARRY334543 | (R)-N4-(3-chloro-4-(thiazol-2-ylmethoxy)phenyl)-N6-(4-methyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

Varlitinib (ARRY334543) is a selective and potentErbB1(EGFR)andErbB2(HER2)inhibitor withIC50of 7 nM and 2 nM, respectively. Phase 2.
In vitro

ARRY334543 behaves as a reversible ATP-competitive inhibitor with nanomolar potency (Kⁱ=1 nM) both in vitro and in cell-based proliferation assays using A431 and BT-474 cells. ARRY334543 is an AKT pathway inhibitor in cells that contains active ErbB-2 receptors. ARRY334543 suppresses ErbB-2 and ErbB-1 phosphorylation in human cancer cells, such as BT-474 with IC50 of 43 nM) and A431 with IC50 of 36 nM) that overexpress ErbB-2 and ErbB-1, respectively.

In vivo

When dosed orally, ARRY334543 prevents growth of human tumor xenografts that overexpress ErbB-1 (A431) or ErbB-2 (MDA-MB-453) in a dose-dependent manner. In mouse xenograft models utilizing the EGFR overexpressing tumor line A431, ARRY334543 demonstrates significant dose related tumor growth prevention when administered orally, BID, for 21 days. ARRY334543 has very good in vivo and in vitro PK/ADME properties and has shown excellent activity in numerous mouse tumor xenograft models including epidermoid (A431), breast (BT-474, MDA-MB-453), non-small cell lung (H1650, A549, 292), colorectal (Lovo, HT-29) and gastric (N87) carcinoma models. In the BT-474 model, ARRY334543 demonstrates significant dose-related tumor growth inhibition (69% at 100 mg/kg/d and 98% at 200 mg/kg/d) with significant regressions at both dose levels. Excellent single agent activity for ARRY334543 in the SK-OV-3 ovarian carcinoma xenograft model as well as additive acitivity to trastuzumab in SK-OV-3, BT-474 and NCI-N87 models has been demonstrated. In the BT-474 model, ARRY334543 displays excellent additive activity and tolerability with docetaxel.
Cell Data

cell lines：

Concentrations：

Incubation Time：

Powder Purity:≥96%

Specifications

Synonyms

ARRY334543 | (R)-N4-(3-chloro-4-(thiazol-2-ylmethoxy)phenyl)-N6-(4-methyl-4, 5-dihydrooxazol-2-yl)quinazoline-4, 6-diamine

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

Varlitinib (ARRY334543) is a selective and potent ErbB1(EGFR) and ErbB2(HER2) inhibitor with IC50 of 7 nM and 2 nM, respectively. Phase 2.

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

Receptor protein-tyrosine kinase erbB-2 inhibitor

Product Properties

• ALogP: 4.2

Names and Identifiers

• Isomeric SMILES: C[C@@H]1COC(=N1)NC2=CC3=C(C=C2)N=CN=C3NC4=CC(=C(C=C4)OCC5=NC=CS5)Cl
• PubChem CID: 42642648
• Molecular Weight: 466.94

Associated Targets(Human)

ERBB4 Tclin Receptor tyrosine-protein kinase erbB-4 (1 Activities)

Discover Target: ERBB4

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

ERBB2 Tclin Receptor tyrosine-protein kinase erbB-2 (2 Activities)

Discover Target: ERBB2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

EGFR Tclin Epidermal growth factor receptor (3 Activities)

Discover Target: EGFR

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Chemical and Physical Properties

• Solubility: Solubility (25°C) In vitro DMSO: 51 mg/mL (200.59 mM); Water: Insoluble; Ethanol: Insoluble