Varlitinib tosylate  (Synonyms: ASLAN001 tosylate; ARRY-334543 tosylate)

Varlitinib (ASLAN001) tosylate is a potent, reversible, small molecule pan-EGFR inhibitor with IC₅₀s of 7, 2, 4 nM for HER1, HER2 and HER4, respectively^[1].

IC50: 7 nM (HER1), 2 nM (HER2), 4 nM (HER4)^[1]

In cell-based assays using tumor cells that over-express EGFR (A431) or ErbB-2 (BT474), Varlitinib tosylate (ARRY-334543) potently inhibits substrate phosphorylation. Varlitinib tosylate is shown to be highly selective for EGFR/ErbB-2, and does not show any significant activity when screened against a panel of 104 kinases^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Varlitinib tosylate treatment potently inhibits tumor growth with complete tumor regression observed at dosing of 100 mg/kg twice a day. After five days of Varlitinib tosylate treatment, phosphorylation of HER1-3, RAS/RAF/MEK/MAPK, p70S6K, S6 ribosomal, 4EBP1, Cdk-2, Cdc-2 and retinoblastoma are strongly inhibited. Varlitinib tosylate treatment results in a significant reduction in survivin and a concomittant increase in Caspase 3 cleavage products^[1]. In murine xenograft models, Varlitinib tosylate (ARRY-334543) demonstrates significant dose-related (25, 50, 100 mg/kg) tumor growth inhibition in A431-derived tumors when administered orally, twice a day, for 21 days^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

811.35

C₃₆H₃₅ClN₆O₈S₃

1146629-86-8

C[C@H]1N=C(NC2=CC3=C(NC4=CC=C(OCC5=NC=CS5)C(Cl)=C4)N=CN=C3C=C2)OC1.O=S(C6=CC=C(C=C6)C)(O)=O.O=S(C7=CC=C(C=C7)C)(O)=O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Hsieh C, et al. Varlitinib to demonstrate anti-tumour efficacy in patient-derived hepatocellular carcinoma xenograft models. Journal of Clinical Oncology 34, no. 15_suppl

  [2]. Miknis G, et al. ARRY-334543, A potent, orally active small molecule inhibitor of EGFR and ErbB-2.Proc Amer Assoc Cancer Res, Volume 46, 2005