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Biological Activity:

(S)-Crizotinib is a novel potent, selective and cell permeable MTH1 inhibitor with an IC₅₀ of ~72 nM. MTH1 is a nucleotide pool sanitizing enzyme. (S)-Crizotinib disrupts nucleotide pool homeostasis via MTH1 inhibition and induces an increase in DNA single-strand breaks in cancer cells. In vivo it can effectively suppress tumor growth in colon carcinoma xenograft model by once per day oral dosing. (R)-Crizotinib, which is (R)-enantiomer of the drug, is inactive against MTH1 in vitro. Loss-of-function of MTH1 impaired growth of KRAS tumor cells. (S)-Crizotinib is a useful chemical probe to further validate MTH1 as a promising novel class of anticancer target.?

How to Use:

In vitro:? (S)-Crizotinib was used at 2-10 μM final concentration in various in vitro and cellular assays.

In vivo: (S)-Crizotinib was dosed to mice orally at 50?mg/kg once per day to impair tumor growth in an SW480 colon carcinoma xenograft model. Formulation is 1% DMSO, 10% ethanol, 10% Cremophor, 10% Tween 80, 69% PBS.?

Reference:

• 1. Huber KV, et al. Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy. (2014) Nature. 508(7495):222-7.

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