2. Academic Validation
  3. Discovery of benzo[d]oxazol-2(3H)-one derivatives as a new class of TNIK inhibitors for the treatment of colorectal cancer

Discovery of benzo[d]oxazol-2(3H)-one derivatives as a new class of TNIK inhibitors for the treatment of colorectal cancer

  • Bioorg Med Chem Lett. 2022 Jul 1;67:128745. doi: 10.1016/j.bmcl.2022.128745.
Xinling Luo 1,  Ruicheng Yang 2,  Yueshan Li 2,  Liting Zhang 2,  Shengyong Yang 2,  Linli Li 3
Affiliations

Affiliations

  • 1 Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, PR China.
  • 2 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
  • 3 Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, PR China. Electronic address: [email protected].
PMID: 35447345 DOI: 10.1016/j.bmcl.2022.128745
Abstract

Colorectal Cancer (CRC) is one of the most commonly diagnosed Cancer types and Traf2- and Nck-interacting kinase (TNIK) has been thought as a potential target for CRC treatment. Herein we report the discovery and structure-activity relationship (SAR) of benzo[d]oxazol-2(3H)-one derivatives as a new class of TNIK inhibitors. The most potent compound 8g showed an IC50 value of 0.050 μM against TNIK. It effectively suppressed proliferation and migration of colorectal Cancer cells. Western blot analysis indicated that 8g could inhibit aberrant transcription activation of Wnt signaling. Collectively, this study provides a potential lead compound for subsequent drug discovery targeting TNIK.

Keywords

Colorectal cancer; Small molecule inhibitor; Structure–activity relationship; TNIK.

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