(S)-crizotinib, MTH1 Inhibitor

(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.

Product information

CAS Number: 1374356-45-2

Molecular Weight: 450.34

Formula: C21H22Cl2FN5O

Synonym:

S crizotinib

ent-crizotinib

3-[(1s)-1-(2,6-Dichloro-3-Fluorophenyl)ethoxy]-5-(1-Piperidin-4-Ylpyrazol-4-Yl)pyridin-2-Amine

3-[(1S)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-[1-(4-piperidinyl)-1H-pyrazol-4-yl]-2-pyridinamine

Chemical Name: (S)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine

Smiles: C[C@H](OC1=CC(=CN=C1N)C1=CN(N=C1)C1CCNCC1)C1=C(Cl)C=CC(F)=C1Cl

InChiKey: KTEIFNKAUNYNJU-LBPRGKRZSA-N

InChi: InChI=1S/C21H22Cl2FN5O/c1-12(19-16(22)2-3-17(24)20(19)23)30-18-8-13(9-27-21(18)25)14-10-28-29(11-14)15-4-6-26-7-5-15/h2-3,8-12,15,26H,4-7H2,1H3,(H2,25,27)/t12-/m0/s1

Technical Data

Appearance: Solid powder

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 42 mg/mL (93.26 mM); EtOH: 22 mg/mL (48.85 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Powder: 4^oC for 1year, -20^oC for 3 years; DMSO: 4^oC for 3 months.

Shelf Life: ≥1080 days if stored properly.

Stock Solution Storage: 0-4^oC for short term (days to weeks), or -20^oC for long term (months).

Drug Formulation: This drug may be formulated in DMSO

HS Tariff Code: 2934.99.9001

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.

References:

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

Products are for research use only. Not for human use.