CX-4945, CK2 (Casein Kinase 2) Inhibitor

CX-4945 (Silmitasertib) is a potent, selective and bioavailable CK2 (Casein Kinase 2) Inhibitor with IC50 of 1 nM. It only inhibits 7 of the 238 kinases by more than 90% at concentration of 0.5 μM, which is 500-fold selectivity over CK2. Although in cell-free systems CX-4945 inhibits FLT3, PIM1, and CDK1 with IC50 of 35 nM, 46 nM, and 56 nM, respectively, but it is inactive against FLT3, PIM1, and CDK1 in cell-based functional assays at 10 µM. CX-4945 exhibits a broad spectrum of antiproliferative activity, correlates with CK2α mRNA and protein levels but not the CK2α' catalytic subunit, the regulatory CK2β subunit, and the PI3K/Akt or PTEN mutational status. Combined inhibition of EGFR and CK2 augments the attenuation of PI3K-Akt-mTOR signaling and the killing of cancer cells. CX-4945 can potentiate senescence by blocking tumour progression in Ptenpc -/- mice. Now CX-4945 is in phase I/II clinical trials to treat cancer.

Product information

CAS Number: 1009820-21-6

Molecular Weight: 349.77

Formula: C19H12ClN3O2

Synonym:

Silmitasertib

Chemical Name: 5-((3-chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid

Smiles: OC(=O)C1=CC2=NC(NC3=CC(Cl)=CC=C3)=C3C=CN=CC3=C2C=C1

InChiKey: MUOKSQABCJCOPU-UHFFFAOYSA-N

InChi: InChI=1S/C19H12ClN3O2/c20-12-2-1-3-13(9-12)22-18-15-6-7-21-10-16(15)14-5-4-11(19(24)25)8-17(14)23-18/h1-10H,(H,22,23)(H,24,25)

Technical Data

Appearance: Solid Power.

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

Solubility: DMSO up to 40 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

CX-4945 was used at 1 µM final concentration in various in vitro assays.

In Vivo:

Oral administration of CX-4945 at 25 mg/kg or 75 mg/kg twice daily displays potent antitumor activity in the BT-474 model, with TGI of 88% and 97%, respectively. In PC3 xenograft model, administration of CX-4945 at 25 mg/kg, 50 mg/kg, or 75 mg/kg causes tumor growth inhibition with TGI of 19%, 40%, and 86%, respectively.

References:

1. Siddiqui-Jain A, et al. CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy.(2010) Cancer Res. 70(24):10288-98.
2. Pierre F, et al. Discovery and SAR of 5-(3-chlorophenylamino)benzo[c][2,6]naphthyridine-8-carboxylic acid (CX-4945), the first clinical stage inhibitor of protein kinase CK2 for the treatment of cancer. (2011) J Med Chem. 54(2):635-54.
3. Kalathur M, et al. A chemogenomic screening identifies CK2 as a target for pro-senescence therapy in PTEN-deficient tumours. (2015) Nat Commun. 6:7227

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

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