(S)-crizotinib

Catalog No.S7505 Batch:S750502

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Technical Data

Formula

C21H22Cl2FN5O
Molecular Weight 450.34 CAS No. 1374356-45-2
Solubility (25°C)* In vitro DMSO 42 mg/mL (93.26 mM)
Ethanol 22 mg/mL (48.85 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description (S)-crizotinib, the (S)-enantiomer of crizotinib, is a potent MTH1 (NUDT1) inhibitor with IC50 of 72 nM in a cell-free assay.
Targets
NUDIX1 [1] MTH1 [1]
(Cell-free assay)
72 nM
In vitro (S)-crizotinib disrupts nucleotide pool homeostasis via MTH1 inhibition, induces an increase in DNA single-strand breaks, and activates DNA repair in human colon carcinoma cells. [1]
In vivo (S)-Crizotinib (50 mg/kg, orally, daily) impairs tumor growth in an SW480 colon carcinoma xenograft model. [1]
Features MTH1 (NUDT1)- selective inhibitor.

Protocol (from reference)

Kinase Assay:

[1]
  • MTH1 catalytic assay

    Half-maximal inhibitory concentrations (IC50) are determined using a luminescence-based assay with some minor modifications. Briefly, serial dilutions of compounds are dissolved in assay buffer (100 mM Tris-acetate pH 7.5, 40 mM NaCl and 10 mM Mg(OAc)2 containing 0.005% Tween-20 and 2 mM dithiothreitol (DTT). Upon addition of MTH1 recombinant protein (final concentration 2 nM), plates are incubated on a plate shaker for 15 min at room temperature. After addition of the substrate dGTP (final concentration 100 µM), 8-oxo-dGTP (final concentration 13.2 µM), or 2-OH-dATP (final concentration 8.3 µM) the generation of pyrophosphate (PPi) as a result of nucleotide triphosphate hydrolysis by MTH1 is monitored over a time course of 15 min using the PPi Light Inorganic Pyrophosphate Assay kit. IC50 values are determined by fitting a dose-response curve to the data points using nonlinear regression analysis using the GraphPad Prism software.
Cell Assay:

[1]
  • Cell lines

    PANC1 and SW480 cells

  • Concentrations

    ~5 礛

  • Incubation Time

    7-10 days

  • Method

    One day before treatment, cells are seeded per well in six-well plates and incubated for 24 h. The next day DMSO (equal to highest amount of compound dilution, maximum 0.2%) or compounds in increasing concentrations were added and cells incubated at 37 °C, 5% CO2, for 7-10 days. After washing with PBS, cells are fixed with ice-cold methanol, stained with crystal violet solution (0.5% in 25% methanol) and left to dry overnight. For quantification of results, ultraviolet absorbance of crystal violet is determined at 595 nm following solubilisation by 70% ethanol. Data are analysed using nonlinear regression analysis using the GraphPad Prism software.
Animal Study:

[1]
  • Animal Models

    SW480 colon carcinoma xenograft mouse model.

  • Dosages

    1% DMSO, 10% ethanol, 10% Cremophor, 10% Tween 80, 69% PBS

  • Administration

    p.o.

Customer Product Validation

Data from [Data independently produced by , , Cancer Letters, 2014, 35(2):215-221.]

Data from [Data independently produced by , , Onco Targets Ther, 2015, 8: 3649-3664.]

Selleck's (S)-crizotinib has been cited by 14 publications

Generation of Human Blood Vessel and Vascularized Cerebral Organoids [ Bio Protoc, 2023, 10.21769/BioProtoc.4870] PubMed: 37969757
Oxidized DNA Precursors Cleanup by NUDT1 Contributes to Vascular Remodeling in PAH [ Am J Respir Crit Care Med, 2020, 10.1164/rccm.202003-0627OC] PubMed: 33021405
Low Replicative Fitness of Neuraminidase Inhibitor-Resistant H7N9 Avian Influenza a Virus With R292K Substitution in Neuraminidase in Cynomolgus Macaques Compared With I222T Substitution [ Antiviral Res, 2020, 178:104790] PubMed: 32272175
Application of a Biphasic Mathematical Model of Cancer Cell Drug Response for Formulating Potent and Synergistic Targeted Drug Combinations to Triple Negative Breast Cancer Cells. [ Cancers (Basel), 2020, 27;12(5)pii: E1087] PubMed: 32349331
Biphasic Mathematical Model of Cell-Drug Interaction That Separates Target-Specific and Off-Target Inhibition and Suggests Potent Targeted Drug Combinations for Multi-Driver Colorectal Cancer Cells. [ Cancers (Basel), 2020, 13;12(2) pii: E436] PubMed: 32069833
Efficient Blockade of Locally Reciprocated Tumor-Macrophage Signaling Using a TAM-avid Nanotherapy [ Sci Adv, 2020, 22;6(21):eaaz8521] PubMed: 32494745
VISAGE Reveals a Targetable Mitotic Spindle Vulnerability in Cancer Cells. [ Cell Syst, 2019, 9(1):74-92.e8] PubMed: 31302152
TLR7/8-agonist-loaded Nanoparticles Promote the Polarization of Tumour-Associated Macrophages to Enhance Cancer Immunotherapy [ Nat Biomed Eng, 2018, 2(8):578-588] PubMed: 31015631
(S)-crizotinib reduces gastric cancer growth through oxidative DNA damage and triggers pro-survival akt signal. [ Cell Death Dis, 2018, 9(6):660] PubMed: 29855474
(S)-crizotinib induces apoptosis in human non-small cell lung cancer cells by activating ROS independent of MTH1. [ J Exp Clin Cancer Res, 2017, 36(1):120] PubMed: 28882182

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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