product name Varlitinib
Description: Varlitinib, also known as ARRY-543 and ASLAN001, is an orally bioavailable, selective and potent ErbB1(EGFR) and ErbB2(HER2) inhibitor with IC50 of 7 nM and 2 nM, respectively. Varlitinib reversibly binds to both EGFR (ErbB-1) and Her-2/neu (ErbB-2) and prevents their phosphorylation and activation, which may result in inhibition of the associated signal transduction pathways, inhibition of cellular proliferation and cell death. EGFR and Her-2 play important roles in cell proliferation and differentiation and are upregulated in various human tumor cell types.
References: Abstracts #3399.
466.94
Formula
C22H19ClN6O2S
CAS No.
845272-21-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 6 mg/mL (12.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
ARRY334543, ASLAN001
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19417090
| In Vitro |
In vitro activity: 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 Kinase Assay: Cell Assay: |
|---|---|
| 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. |
| Animal model | |
| Formulation & Dosage | |
| References | Abstracts #3399. |
