A novel FAK-degrading PROTAC molecule exhibited both anti-tumor activities and efficient MDR reversal effects

Chuang HH, Zhen YY, Tsai YC, Chuang CH, Hsiao M, Huang MS, et al. FAK in cancer: from mechanisms to therapeutic strategies. Int J Mol Sci. 2022;23:1726.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dawson JC, Serrels A, Stupack DG, Schlaepfer DD, Frame MC. Targeting FAK in anticancer combination therapies. Nat Rev Cancer. 2021;21:313–24.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Spallarossa A, Tasso B, Russo E, Villa C, Brullo C. The development of FAK inhibitors: a five-year update. Int J Mol Sci. 2022;23:6381.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Luo M, Zhao X, Chen S, Liu S, Wicha MS, Guan JL. Distinct FAK activities determine progenitor and mammary stem cell characteristics. Cancer Res. 2013;73:5591–602.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cromm PM, Samarasinghe KTG, Hines J, Crews CM. Addressing kinase-independent functions of fak via PROTAC-mediated degradation. J Am Chem Soc. 2018;140:17019–26.

Article  CAS  PubMed  Google Scholar 

Law RP, Nunes J, Chung CW, Bantscheff M, Buda K, Dai H, et al. Discovery and characterisation of highly cooperative FAK-degrading PROTACs. Angew Chem Int Ed Engl. 2021;60:23327–34.

Article  CAS  PubMed  Google Scholar 

Popow J, Arnhof H, Bader G, Berger H, Ciulli A, Covini D, et al. Highly Selective PTK2 proteolysis targeting chimeras to probe focal adhesion kinase scaffolding functions. J Med Chem. 2019;62:2508–20.

Article  CAS  PubMed  Google Scholar 

Gao H, Wu Y, Sun Y, Yang Y, Zhou G, Rao Y. Design, synthesis, and evaluation of highly potent FAK-targeting PROTACs. ACS Med Chem Lett. 2020;11:1855–62.

Article  CAS  PubMed  Google Scholar 

Diaz Osterman CJ, Ozmadenci D, Kleinschmidt EG, Taylor KN, Barrie AM, Jiang S, et al. FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy. Elife. 2019;8:e47327.

Article  PubMed  PubMed Central  Google Scholar 

Ji N, Yang Y, Cai CY, Lei ZN, Wang JQ, Gupta P, et al. VS-4718 Antagonizes multidrug resistance in ABCB1- and ABCG2-overexpressing cancer cells by inhibiting the efflux function of ABC transporters. Front Pharmacol. 2018;9:1236.

Article  CAS  Google Scholar 

Verastem Oncology Announces Positive Data and Regulatory Update from Planned Interim Analysis of Registration-Directed Phase 2 RAMP-201 Trial of Avutometinib and Defactinib in Recurrent Low-Grade Serous Ovarian Cancer [updated 2023 JAN 24; cited 2024 MAY 13]. Available from: https://investor.verastem.com/news-releases/news-release-details/verastem-oncology-announces-positive-data-and-regulatory-update.

InxMed Releases Data Demonstrating Ifebemtinib (IN10018) Trending Toward Survival Benefit at ESMO 2023 [updated 2023 Oct 22; cited 2024 MAY 13]. Available from: https://www.prnewswire.com/news-releases/inxmed-releases-data-demonstrating-ifebemtinib-in10018-trending-toward-survival-benefit-at-esmo-2023-301963834.html.

Hu X, Ouyang Q, yan M, Wenyan C, Cang S, Huang Y, et al. 398P A phase Ib/II study of IN10018/FAKi in combination with pegylated liposomal doxorubicin (PLD) and toripalimab in metastatic triple-negative breast cancer (TNBC): IN10018-010. Ann Oncol. 2023;34:S348–9.

Article  Google Scholar 

Wu L, Wang J, Wang L, Lu W, Wang K, Lin A, et al. A phase Ib study of IN10018 in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2022;40:5567.

Article  Google Scholar 

Zhao F, Yang Z, Gu X, Feng L, Xu M, Zhang X. miR-92b-3p Regulates cell cycle and apoptosis by targeting CDKN1C, Thereby affecting the sensitivity of colorectal cancer cells to chemotherapeutic drugs. Cancers. 2021;13:3323.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fang Y, Sun J, Zhong X, Hu R, Gao J, Duan G, et al. ES2 enhances the efficacy of chemotherapeutic agents in ABCB1-overexpressing cancer cells in vitro and in vivo. Pharmacol Res. 2018;129:388–99.

Article  CAS  PubMed  Google Scholar 

Zhang WL, Li N, Shen Q, Fan M, Guo XD, Zhang XW, et al. Establishment of a mouse model of cancer cachexia with spleen deficiency syndrome and the effects of atractylenolide I. Acta Pharmacol Sin. 2020;41:237–48.

Article  CAS  PubMed  Google Scholar 

Wang P, Wu J, Wang Q, Zhuang S, Zhao J, Yu Y, et al. Baicalin inhibited both the Furin/TGFβ1/Smad3/TSP-1 pathway in endothelial cells and the AKT/Ca2+/ROS pathway in platelets to ameliorate inflammatory coagulopathy. Eur J Pharmacol. 2023;949:175674.

Article  CAS  PubMed  Google Scholar 

Dale B, Cheng M, Park KS, Kaniskan H, Xiong Y, Jin J. Advancing targeted protein degradation for cancer therapy. Nat Rev Cancer. 2021;21:638–54.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schneider M, Radoux CJ, Hercules A, Ochoa D, Dunham I, Zalmas LP, et al. The PROTACtable genome. Nat Rev Drug Discov. 2021;20:789–97.

Article  CAS  PubMed  Google Scholar 

Pettersson M, Crews CM. PROteolysis TArgeting Chimeras (PROTACs) - past, present and future. Drug Discov Today Technol. 2019;31:15–27.

Article  PubMed  PubMed Central  Google Scholar 

Yuen AR, Sikic BI. Multidrug resistance in lymphomas. J Clin Oncol. 1994;12:2453–9.

Article  CAS  PubMed  Google Scholar 

Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, et al. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science. 2009;323:1718–22.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Luo J, Yao JF, Deng XF, Zheng XD, Jia M, Wang YQ, et al. 14, 15-EET induces breast cancer cell EMT and cisplatin resistance by up-regulating integrin αvβ3 and activating FAK/PI3K/AKT signaling. J Exp Clin Cancer Res. 2018;37:23.

Article  PubMed  PubMed Central  Google Scholar 

Lorusso G, Wyss CB, Kuonen F, Vannini N, Billottet C, Duffey N, et al. Connexins orchestrate progression of breast cancer metastasis to the brain by promoting FAK activation. Sci Transl Med. 2022;14:eaax8933.

Article  CAS  PubMed  Google Scholar 

Shen M, Jiang YZ, Wei Y, Ell B, Sheng X, Esposito M, et al. Tinagl1 suppresses triple-negative breast cancer progression and metastasis by simultaneously inhibiting integrin/FAK and EGFR signaling. Cancer Cell. 2019;35:64–80.e7.

Article  CAS  PubMed  Google Scholar 

Rigiracciolo DC, Nohata N, Lappano R, Cirillo F, Talia M, Adame-Garcia SR, et al. Focal Adhesion Kinase (FAK)-Hippo/YAP transduction signaling mediates the stimulatory effects exerted by S100A8/A9-RAGE system in triple-negative breast cancer (TNBC). J Exp Clin Cancer Res. 2022;41:193.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shen J, Cao B, Wang Y, Ma C, Zeng Z, Liu L, et al. Hippo component YAP promotes focal adhesion and tumour aggressiveness via transcriptionally activating THBS1/FAK signalling in breast cancer. J Exp Clin Cancer Res. 2018;37:175.

Article  PubMed  PubMed Central  Google Scholar 

Zhang L, Qu J, Qi Y, Duan Y, Huang YW, Zhou Z, et al. EZH2 engages TGFβ signaling to promote breast cancer bone metastasis via integrin β1-FAK activation. Nat Commun. 2022;13:2543.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fan H, Guan JL. Compensatory function of Pyk2 protein in the promotion of focal adhesion kinase (FAK)-null mammary cancer stem cell tumorigenicity and metastatic activity. J Biol Chem. 2011;286:18573–82.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Weis SM, Lim ST, Lutu-Fuga KM, Barnes LA, Chen XL, Göthert JR, et al. Compensatory role for Pyk2 during angiogenesis in adult mice lacking endothelial cell FAK. J Cell Biol. 2008;181:43–50.

留言 (0)

沒有登入
gif