CB-6644

CB-6644 is a novel allosteric selective inhibitor of the ruvbl1/2 complex with anti-cancer activity. CB-6644 blocks the ATPase activity of RUVBL1/2 with an IC50 of 15 nM. CB-6644 interacts specifically with RUVBL1/2 in cancer cells, leading to cell death. Importantly, drug-acquired-resistant cell clones have amino acid mutations in either RUVBL1 or RUVBL2, suggesting that cell killing is an on-target consequence of RUVBL1/2 engagement. In xenograft models of acute myeloid leukemia and multiple myeloma, CB-6644 significantly reduced tumor growth without obvious toxicity.

Product information

CAS Number: 2316817-88-4

Molecular Weight: 573.06

Formula: C29H34ClFN4O5

Chemical Name: 5-Chloro-2-ethoxy-4-fluoro-N-(4-((3-(methoxymethyl)-1-oxo-6, 7-dihydro-1H, 5H-benzo[c]pyrazolo[1, 2-a][1, 2]diazepin-2-yl)amino)-2, 2-dimethyl-4-oxobutyl)benzamide

Smiles: COCC1=C(NC(=O)CC(C)(C)CNC(=O)C2=CC(Cl)=C(F)C=C2OCC)C(=O)N2C3=CC=CC=C3CCCN21

InChiKey: VYCOZEBCSAQCES-UHFFFAOYSA-N

InChi: InChI=1S/C29H34ClFN4O5/c1-5-40-24-14-21(31)20(30)13-19(24)27(37)32-17-29(2,3)15-25(36)33-26-23(16-39-4)34-12-8-10-18-9-6-7-11-22(18)35(34)28(26)38/h6-7,9,11,13-14H,5,8,10,12,15-17H2,1-4H3,(H,32,37)(H,33,36)

Technical Data

Appearance: Solid Power

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

Solubility: DMSO : 100 mg/mL (174.50 mM; Need ultrasonic)

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:

CB-6644 (20 µM) interacts with the RUVBL1/2 complex in Ramos cells. CB-6644 (0.001-10 μM; 72 hours) potently kills 123 cell lines (including HCT116, NCI-1975, and HT29 cells) with an EC50 range of 41 to 785 nM.

In Vivo:

CB-6644 (150 mg/kg, oral administration, 10 days of treatment for SCID-beige mice bearing Ramos xenograft models, 30 days of treatment for SCID-beige mice bearing RPMI8226 xenograft models) has antitumor activity in xenograft tumor models with tumor growth inhibitions (TGIs) of 68 and 81%, respectively in Ramos xenograft models and RPMI8226 xenograft models.

References:

1. Assimon VA, et al. CB-6644 Is a Selective Inhibitor of the RUVBL1/2 Complex with Anticancer Activity. ACS Chem Biol. 2019 Feb 15;14(2):236-244.

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