| Description |
ARRY-380 (ONT-380) is an orally bioavailable inhibitor of the human epidermal growth factor receptor tyrosine kinase ErbB-2 (also called HER2) with potential antineoplastic activity. |
|
Targets
|
| p95 HER2 [2] |
ErbB2 [2] |
EGFR [2] |
| 7 nM |
8 nM |
4000 nM |
|
| In vitro |
The compound is a reversible, ATP-competitive inhibitor with nanomolar potency against ErbB2 in both in vitro and in cell-based assays[1]. In
cell-based assays, ARRY-380 is ~500-fold selective for HER2 vs. EGFR and is equipotent against truncated p95-HER2[2].
|
| In vivo |
In vivo, ARRY-380 significantly inhibits tumor growth in multiple HER2-dependent tumor xenograft models[2]. It shows excellent activity in numerous mouse tumor models including breast (BT-474, MDA-MB-453), ovarian (SKOV-3) and gastric (N87) carcinoma models. In the BT-474 model, ARRY-380 demonstrated significant dose-related tumor growth inhibition (TGI; 50% at 50 mg/kg/d and 96% at 100 mg/kg/d) with numerous partial regressions (>50% reduction from baseline size)[1].
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COA
HPLC