AC480 / BMS - LARVOL DELTA

BMS-599626, a Highly Selective Pan-HER Kinase Inhibitor, Antagonizes ABCG2-Mediated Drug Resistance. (PubMed, Cancers (Basel)) - "As shown by the cytotoxicity assay results, BMS-599626, at noncytotoxic concentrations, sensitizes ABCG2-overexpressing cells to topotecan and mitoxantrone, two well-known substrates of ABCG2. Our in-silico docking study also supports the interaction of BMS-599626 with the substrate-binding site of ABCG2. Taken together, these results suggest that administration of chemotherapeutic drugs, along with nanomolar concentrations (300 nM) of BMS-599626, may be effective against ABCG2-mediated MDR in clinical settings."

Journal • ABCG2

Dual HER/VEGF receptor targeting inhibits in vivo ovarian cancer tumor growth (Mol Cancer Ther) - PMID: 24130056; "...ovarian cancer xenografts grown intraperitoneally in athymic nude mice were tested in response to AC480 (pan HER inhibitor, "HERi"), cediranib (pan VEGFR inhibitor "VEGFRi"), or BMS-690514 (combined HER/VEGFR inhibitor "EVRi"). EVRi was superior to both HERi and VEGFRi in terms of tumor growth, final tumor weight and progression-free survival."

Preclinical • Oncology • Ovarian Cancer

A pharmacokinetic (PK) study of AC480 administered twice daily in patients with surgically resectable, recurrent malignant glioma (MG) not on enzyme-inducing antiepileptic drug (EIAED) (ASCO 2011) - Abstract not available

Oncology

Safety study for intravenous (IV) AC480 (AC480IV) to treat advanced solid tumors (clinicaltrials.gov) - P1, N=100; Recruiting -> Active, not recruiting; Completion date: Apr 2012 -> Mar 2013

Completion date • Enrollment closed • Oncology

Role of EGFR/ErbB2 and PIK/AKT/e-NOS in Lycium barbarum polysaccharides Ameliorating Endothelial Dysfunction Induced by Oxidative Stress. (PubMed, Am J Chin Med) - "In addition, Ang II treatment increased the expression of EGFR and p-EGFR (Try1172) and which can be inhibited by LBP. On the contrary, expression of ErbB2, p-ErbB2 (Try1248), PIK, p-e-NOS (Ser1177) (), and p-AKT (Ser473) () was inhibited by Ang II treatment and which can be increased by LBP. Treatment of the cells with inhibitors showed that the regulation of p-e-NOS and p-AKT expression by Ang II and LBP can be blocked by PIK inhibitor wortmannin but not EGFR and ErbB2 inhibitor AC480. Taken together, our results suggested that LBP plays a critical role in maintaining the integrality of blood vessel endothelium through reduced production of ROS via regulating the activity of EGFR, ErbB2, PIK/AKT/e-NOS, and which may offer a novel therapeutic option in the management of endothelial dysfunction."

Journal

Phase I safety, pharmacokinetic and pharmacodynamic trial of BMS-599626 (AC480), an oral pan-HER receptor tyrosine kinase inhibitor, in patients with advanced solid tumors. (PubMed, Ann Oncol) - No abstract available.

Clinical • Journal • P1 data • PK/PD data