Compound for inhibiting tankyrase and medical use thereof

• Main Authors: RYU HWANI, KIM BO KYOUNG, BAE SU YEAL, CHOIYOUNG, KIM JAE SUNG, SONG JIE YOUNG, HWANG SANG GU, SEO HYE RAN, AHN JI YEON, KIM YOUNG HOON, KIM HYO JEONG
• Format: Patent
• Language: English; Korean
• Published: 25.05.2023
• Subjects: HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The present invention relates to a compound for inhibiting tankyrase and medical use thereof. The compound according to the present invention inhibits tankyrase (TNKS) enzyme activity, inhibits beta-catenin (β-catenin) target gene expression and active beta-catenin protein expression, stabilizes an AXIN2 protein level, and has anticancer activity in human colon cancer cell lines. Accordingly, the compound can be used as an anticancer drug. In addition, the compound shows a synergistic effect in the anticancer activity when used in combination with conventional anticancer drugs, 7-Ethyl-10-hydroxycamptothecin (SN-38) or fluorouracil (5-FU), and thus can be used as a combination therapy with the conventional anticancer drugs. The present invention provides a pharmaceutical composition for treating or preventing tankyrase-related diseases containing a compound represented by chemical formula 1 or a pharmaceutically acceptable salt thereof. 본 발명은 탄키라제 억제용 화합물 및 이의 의학적 용도에 관한 것으로, 본 발명에 따른 화합물은 탄키라제(TNKS) 효소 활성을 억제하며, 베타-카테닌(β-catenin) 타겟 유전자 발현과 활성 베타-카테닌 단백질 발현을 억제하고, AXIN2 단백질 수준을 안정화 시키며, 인체 대장암 세포주에서 항암활성을 나타내므로, 상기 화합물을 항암제로 활용할 수 있고, 또한, 상기 화합물은 기존 항암제인 7-에틸-10-하이드록시캄프토테신(7-Ethyl-10-hydroxycamptothecin; SN-38] 또는 플루오로우라실(fluorouracil; 5-FU)과 병용 시 항암활성에서 시너지 효과를 나타내므로, 기존 항암제와의 병용요법으로 활용할 수 있다.