2. Academic Validation
  3. CB-6644 Is a Selective Inhibitor of the RUVBL1/2 Complex with Anticancer Activity

CB-6644 Is a Selective Inhibitor of the RUVBL1/2 Complex with Anticancer Activity

  • ACS Chem Biol. 2019 Feb 15;14(2):236-244. doi: 10.1021/acschembio.8b00904.
Victoria A Assimon 1,  Yangzhong Tang 1,  Jesse D Vargas 1,  Grace J Lee 1,  Zhi Yong Wu 1,  Kenny Lou 1,  Bing Yao 1,  Mary-Kamala Menon 1,  Ariel Pios 1,  Kristy C Perez 1,  Antonett Madriaga 1,  Peter K Buchowiecki 1,  Mark Rolfe 1,  Laura Shawver 1,  Xianyun Jiao 1,  Ronan Le Moigne 1,  Han-Jie Zhou 1,  Daniel J Anderson 1
Affiliations

Affiliation

  • 1 Cleave Biosciences, Inc. , Burlingame , California 94010 , United States.
PMID: 30640450 DOI: 10.1021/acschembio.8b00904
Abstract

RUVBL1 and RUVBL2 are ATPases associated with diverse cellular activities (AAAs) that form a complex involved in a variety of cellular processes, including chromatin remodeling and regulation of gene expression. RUVBLs have a strong link to oncogenesis, where overexpression is correlated with tumor growth and poor prognosis in several Cancer types. CB-6644, an allosteric small-molecule inhibitor of the ATPase activity of the RUVBL1/2 complex, 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. This work demonstrates the therapeutic potential of targeting RUVBLs in the treatment of Cancer and establishes a chemical entity for probing the many facets of RUVBL biology.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-114429
    99.88%, RUVBL1/2抑制剂
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