A chemical perspective on the modulation of TEAD transcriptional ...
网页2022年12月5日 · In a mouse xenograft model of NCI–H226 cells, oral administration of VT3989 at 3 mg/kg achieved partial tumor regression and inhibited expression of CTGF and Cyr61 genes in a dose-dependent manner, indicating on-target activity.
Therapeutic targeting of TEAD transcription factors in cancer
网页2023年5月1日 · TEAD transcription factors pair with YAP and TAZ to orchestrate various transcriptional programs of cell proliferation and cell death suppression that promote cancer development. The structure of TEAD complexed with YAP/TAZ reveals several possible avenues for pharmacological modulation, making TEAD an attractive therapeutic target.
Therapeutic targeting of TEAD transcription factors in cancer
网页2023年5月1日 · VT3989 is a TEAD autopalmitoylation inhibitor from Vivace Therapeutics that effectively inhibits cell proliferation, but only in NF2-deficient mesothelioma cell lines (NCI-H226, NCI-H2052, and NCI-H2373) with an IC 50 in the 10 nM range. In the NF2-deficient NCI-H226 CDX model, significant inhibition of …
网页VT3989 is a TEAD autopalmitoylation inhibitor. (A) YAP reporter assay and thermal shift assays show that VT3989 suppresses TEAD transcriptional activity and directly interacts with TEAD proteins. (B) Acyl -PEGyl Exchange GelShift (APEGS) Assay: VT3989 blocks palmitoylation of endogenous TEAD1 in NCI-H2373 mesothelioma cells.. A. B.
网页First-in-class, first-in-human phase 1 trial of VT3989, an inhibitor of Yes-Associated Protein (YAP)/Transcriptional Enhancer Activator Domain (TEAD), in patients with advanced solid tumors enriched for malignant mesothelioma and other tumors with neurofibromatosis 2 (NF2) mutations.
Abstract 5364: The TEAD autopalmitoylation inhibitor VT3989 …
网页2022年6月15日 · In in vitro cell proliferation assays, VT3989 showed strong to very strong synergy in combination with osimertinib in several EGFR mutant NSCLC cell lines tested. In vivo, we observed strong VT3989 and osimertinib combination effect in NCI-H1975 and HCC827 cell line-derived xenograft models.
Abstract B088: VT3989, the first-in-class and first-in-human TEAD …
网页2023年12月1日 · In in vitro assays as well as in vivo studies using cell line derived (CDX) and patient derived (PDX) xenograft models, VT3989 enhanced the efficacy and durability of clinically approved EGFR inhibitors (osimertinib, lazertinib), MET inhibitors (savolitinib, capmatinib), EGFR-MET bispecific antibody (amivantinib), KRAS-G12C inhibitors ...
网页VT3989, currently in clinical testing, was evaluated for effect on emerging drug tolerant persister/dominant cancer cells and drug resistance. Palmitoylation of a conserved cysteine is required for TEAD interaction with YAP. The palmitate is buried in a central pocket in the YAP-binding domain of TEAD.
网页NF2-de cient mesothelioma, often due to biallelic inactivating NF2 muta-fi tions (NF2m), is dependent on interactions between YAP and TEAD for growth. VT3989 is an oral, highly potent and selective inhibitor of TEAD palmitoylation and blocks YAP function, a pathway previously considered undruggable.
Vivace 发布首个靶向Hippo-YAP通路的癌症药物临床验证 - 知乎
网页2023年4月24日 · 根据AACR年会网站上发布的研究结果摘要（CT006），Vivace表示，其I期试验（NCT04665206）的数据显示，其主要候选药物VT3989在晚期恶性间皮瘤和其他伴有神经纤维瘤病2（NF2）突变的肿瘤患者中取得了持久的抗肿瘤反应。. 69例患者中有7例显示肿瘤缩小符合部分缓解的 ...