Varlitinib

2 years -80 in solvent

Administered via p.o.

ARRY334543 has been under phase II clinical trial in the treatment of advanced cancer and pancreatic cancer.

2 nM, 2 nM, 2 nM, 2 nM, 2 nM, 2 nM

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. [2]

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