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AB286212

(S)-Crizotinib

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MW 450.3 Da, Purity >98%. (S)-crizotinib is a low nanomolar inhibitor of 7,8-dihydro-8-oxoguanine triphosphatase (MTH1 or NUDT1) whereas the (R)-enantiomer shows IC₅₀ values in the micromolar range. MTH1 aids in RAS-transformed cells to overcome oncogene-induced senescence by preventing reactive oxygen species (ROS)-induced DNA damage. The average IC₅₀ values for (S)-crizotinib and the MTH1 substrates 8-oxo-dGTP and 2-OH-dATP is 330 nM and 408 nM respectively. In vitro Kd measurements indicate that (S)-crizotinib is considerably less potent than the (R)-enantiomer against the targets ALK, MET and ROS1. (S)-crizotinib reduces tumor volume by more than 50% in mouse xenograft studies using SW480 cells.

Key facts

CAS number

1374356-45-2

Purity

>98%

Form

Solid

form

Molecular weight

450.3 Da

Molecular formula

C<sub>2</sub><sub>1</sub>H<sub>2</sub><sub>2</sub>Cl<sub>2</sub>FN<sub>5</sub>O

PubChem

56671814

Nature

Synthetic

Solubility

~ 5 mg/ml in DMSO (warm if needed)

Biochemical name

(S)-crizotinib

Biological description

(S)-crizotinib is a low nanomolar inhibitor of 7,8-dihydro-8-oxoguanine triphosphatase (MTH1 or NUDT1) whereas the (R)-enantiomer shows IC₅₀ values in the micromolar range. MTH1 aids in RAS-transformed cells to overcome oncogene-induced senescence by preventing reactive oxygen species (ROS)-induced DNA damage. The average IC₅₀ values for (S)-crizotinib and the MTH1 substrates 8-oxo-dGTP and 2-OH-dATP is 330 nM and 408 nM respectively. In vitro Kd measurements indicate that (S)-crizotinib is considerably less potent than the (R)-enantiomer against the targets ALK, MET and ROS1. (S)-crizotinib reduces tumor volume by more than 50% in mouse xenograft studies using SW480 cells.

Canonical smiles

CC(C1=C(C=CC(=C1Cl)F)Cl)OC2=C(N=CC(=C2)C3=CN(N=C3)C4CCNCC4)N

Isomeric smiles

C[C@@H](C1=C(C=CC(=C1Cl)F)Cl)OC2=C(N=CC(=C2)C3=CN(N=C3)C4CCNCC4)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

InChiKey

KTEIFNKAUNYNJU-LBPRGKRZSA-N

IUPAC Name

3-[(1S)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine

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Product details

This product is manufactured by BioVision, an Abcam company and was previously called B3071 (S)-Crizotinib. B3071-25 is the same size as the 25 mg size of ab286212.
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Properties and storage information

Shipped at conditions
Ambient - Can Ship with Ice
Appropriate long-term storage conditions
-20°C
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Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

MTH1 also known as NUDT1 is a protein that hydrolyzes oxidized nucleotides preventing their incorporation into DNA and RNA. It has a mass approximately 23 kDa and is expressed widely with heightened expression in cancer cells where oxidative stress is prevalent. Interferon gamma (IFN-γ) is a cytokine involved in immune responses with a mass of 20 kDa. It is expressed by activated T cells and natural killer cells. ALK or anaplastic lymphoma kinase is a receptor tyrosine kinase with a mass close to 180 kDa mainly expressed in the nervous system and implicated in neural development. Met also known as hepatocyte growth factor receptor (HGFR) or c-Met is another receptor tyrosine kinase with a mass of around 145 kDa and is expressed in various epithelial cells.
Biological function summary

MTH1 plays a protective role by clearing oxidized dNTPs safeguarding genomic integrity. It operates mainly as a monomer. Interferon gamma orchestrates immune regulation by activating macrophages and promoting antigen presentation often working as part of a larger cytokine signaling network. Meanwhile ALK transduces signals for cell growth when bound by its ligand through pathways that include MAPK and PI3K. Met upon binding its ligand HGF triggers epithelial cell proliferation and motility acting as a critical player in tissue regeneration and repair.

Pathways

MTH1 participates in DNA repair pathways interacting with DNA polymerases that mitigate oxidative damage. Interferon gamma engages in the Jak-STAT signaling pathway which influences gene expression related to immune response and inflammation. ALK and Met both integrate into signaling cascades such as the RAS-MAPK and PI3K-Akt pathways often leading to effects on cell cycle progression and survival. These pathways connect ALK and Met with proteins like KRAS and Akt that are vital for cellular responses.

Oxidative DNA damage links MTH1 to various cancers with crizotinib being a related inhibitor showing relevance in treatments targeting oxidative stress. Aberrant signaling involving Interferon gamma correlates with autoimmune conditions like rheumatoid arthritis reflecting its impact on immune-related disorders. ALK becomes significant in specific malignancies like non-small cell lung cancer (NSCLC) where gene rearrangements drive tumorigenesis. Met when dysregulated associates with metastatic cancers with connections to proteins such as HGF that exacerbate tumor invasion and growth.
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Product protocols

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