CAS 1374356-45-2|(S)-Crizotinib

Introduction：Basic information about CAS 1374356-45-2|(S)-Crizotinib, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. (S)-Crizotinib BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Articles1
6. Synonyms

Common Name	(S)-Crizotinib
CAS Number	1374356-45-2	Molecular Weight	450.33700
Density	/	Boiling Point	/
Molecular Formula	C₂₁H₂₂Cl₂FN₅O	Melting Point	/
MSDS	ChineseUSA	Flash Point	/

Names

Name	2-Pyridinamine, 3-[(1S)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(4-piperidinyl)-1H-pyrazol-4-yl]-
Synonym	More Synonyms

(S)-Crizotinib BiologicalActivity

Description	(S)-Crizotinib, a (S)-enantiomer of crizotinib, is a potent and selective MTH1 (mutT homologue) inhibitor with an IC50 of 330 nM. (S)-Crizotinib disrupts nucleotide pool homeostasis via MTH1 inhibition, induces an increase in DNA single strand breaks, activates DNA repair in human colon carcinoma cells, and effectively suppresses tumour growth in animal models[1].
Related Catalog	Signaling Pathways >>Apoptosis >>ApoptosisResearch Areas >>Cancer
Target	IC50: 330 nM (MTH1)[1]
In Vitro	(S)-crizotinib (0.625-80 μM; 24 hours) decreases the viability of NCI-H460, H1975 and A549 cells with IC50 values of 14.29, 16.54 and 11.25 μM, respectively[2]. (S)-crizotinib (10-30 μM; 24 hours) induces NCI-H460, H1975 and A549 cells apoptosis[2]. (S)-crizotinib (10-30 μM; 24 hours) decreases Bcl-2: Bax ratio. (S)-crizotinib decreases B cell lymphoma 2 (Bcl-2), and Bcl-2 associated protein x (Bax) is either unaltered (H460 cells) or shows an increase (H1975 cells)[2]. (S)-Crizotinib induces apoptosis in human non-small cell lung cancer (NSCLC) cells by activating ROS-dependent ER stress apoptotic pathway independent of mutT homologue (MTH1)[2]. Cell Viability Assay[2] Cell Line: NSCLC cells, NCI-H460, H1975 and A549 cells Concentration: 0.625, 1.25, 2.5, 5, 10, 20, 40, 60, 80 μM Incubation Time: 24 hours Result: Decreased the viability of NCI-H460, H1975 and A549 cells with IC50 values of 14.29, 16.54 and 11.25 μM, respectively. Apoptosis Analysis[2] Cell Line: NSCLC cells, NCI-H460, H1975 and A549 cells Concentration: 10, 20 or 30 μM Incubation Time: 24 hours Result: Induced cells apoptosis. Western Blot Analysis[2] Cell Line: NSCLC cells, NCI-H460, H1975 and A549 cells Concentration: 10, 20 or 30 μM Incubation Time: 24 hours Result: Decreased Bcl-2: Bax ratio.
In Vivo	(S)-crizotinib (7.5 or 15 mg/kg; intraperitoneal injections; once daily for 10 days) results in significant reductions in both tumor volume and tumor weight[2]. Animal Model: Five-week-old, athymic BALB/c nu/nu female mice (17-19 g) with NCI-H460 cells[2] Dosage: 7.5 or 15 mg/kg Administration: Intraperitoneal injections; once daily for 10 days Result: Resulted in significant reductions in both tumor volume and tumor weight.
References	[1]. Huber KV, et al. Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy. Nature. 2014 Apr 10;508(7495):222-7. [2]. Dai X, et al. (S)-crizotinib induces apoptosis in human non-small cell lung cancer cells by activating ROS independent of MTH1. J Exp Clin Cancer Res. 2017 Sep 7;36(1):120.

Chemical & Physical Properties

Molecular Formula	C₂₁H₂₂Cl₂FN₅O
Molecular Weight	450.33700
Exact Mass	449.11900
PSA	77.99000
LogP	5.94770
InChIKey	KTEIFNKAUNYNJU-LBPRGKRZSA-N
SMILES	CC(Oc1cc(-c2cnn(C3CCNCC3)c2)cnc1N)c1c(Cl)ccc(F)c1Cl
Storage condition	-20℃

Safety Information

RIDADR	NONH for all modes of transport

Articles1

Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1.

Onco. Targets Ther. 8 , 3649-64, (2015)

Inhibition of the nucleotide pool sanitizing enzyme MTH1 causes extensive oxidative DNA damages and apoptosis in cancer cells and hence may be used as an anticancer strategy. As natural products have ...

Synonyms

(S)-Crizotinib

(S)-crizotinib

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