Initial testing (stage 1) of M6620 (formerly VX-970), a novel ATR inhibitor, alone and combined with cisplatin and melphalan, by the Pediatric Preclinical Testing Program.

ABSTRACT:

Background

M6620 is a novel inhibitor of the DNA damage repair enzyme ATR, and has potentiated the activity of cisplatin and irinotecan in non-small cell lung cancer and colon cancer xenografts, respectively.

Procedures

M6620 was tested in vitro at concentrations ranging from 1.0 nM to 10.0 μM and at 75 nM in combination with cisplatin or melphalan. M6620 was tested against 24 solid tumor xenografts alone and in combination with cisplatin. Cisplatin was administered intraperitoneally on days 1 and 8 at a dose of 5 mg/kg. M6620 was administered intravenously on days 2 and 9 at 20 mg/m² approximately 16 hr after cisplatin.

Results

The median relative IC₅₀ (rIC₅₀ ) value for M6620 was 0.19 μM (range 0.03-1.38 μM). M6620 reduced the mean I

SUBMITTER: Kurmasheva RT 

PROVIDER: S-EPMC5876726 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature