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Overview
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Background
IC50: 0.17, 0.53, and 0.16 μM for A375, COLO829 and COLO205 cell lines, respectively.PLX7904 is a potent and selective BRAF inhibitor. Oncogenic activation of BRAF leads to cancer growth by constitutively promoting RAS-independent mitogen-activated protein kinase pathway signalling. Therefore, BRAF inhibitors have provided substantially improved treatment of metastatic melanoma.In vitro: Previous study showed that PLX7904 could inhibit the in-vitro growth of two melanoma cell lines (A375 and COLO829) and an additional human colorectal cancer cell line COLO205 expressed BRAFV600E. The gene expression changes in B9 cells treated with vemurafenib and PLX7904 were compared, and results demonstrated that vemurafenib could alter transcription of 191 mouse genes by at least 1.9-fold, while PLX7904 had minimal effects. Moreover, both vemurafenib and its analogue PLX4720 werer able to stimulate B9 colony formation, whereas PLX7904 was not [1]. In vivo: Animal study showed that both PLX7904 and vemurafenib could produce similar anti-tumour effects in a subcutaneous COLO205 xenograft model with matching doses at 25 mg/kg twice daily and plasma exposures. In addition, when evaluated in vivo, subcutaneous B9-tumour growth was accelerated by vemurafenib but not by PLX7904 when administered at the same dose [1]. Clinical trial: Up to now, PLX7904 is still in the preclinical development stage.
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