909563-33-3Relevant academic research and scientific papers
Discovery of Novel Pyrrolo[2,3-d]pyrimidine-based Derivatives as Potent JAK/HDAC Dual Inhibitors for the Treatment of Refractory Solid Tumors
Liang, Xuewu,Tang, Shuai,Liu, Xuyi,Liu, Yingluo,Xu, Qifu,Wang, Xiaomin,Saidahmatov, Abdusaid,Li, Chunpu,Wang, Jiang,Zhou, Yu,Zhang, Yingjie,Geng, Meiyu,Huang, Min,Liu, Hong
, p. 1243 - 1264 (2022)
It remains a big challenge to develop HDAC inhibitors effective for solid tumors. Previous studies have suggested that the feedback activation of JAK-STAT3 pathway represents a key mechanism leading to resistance to HDAC inhibitors in breast cancer, suggesting the therapeutic promise of JAK/HDAC dual inhibitors. In this work, we discovered a series of pyrrolo[2,3-d]pyrimidine-based derivatives as potent JAK and HDAC dual inhibitors. Especially, compounds 15d and 15h potently inhibited JAK1/2/3 and HDAC1/6 and displayed antiproliferative and proapoptotic activities in triple-negative breast cancer cell lines. Besides, compounds 15d and 15h also diminished the activation of LIFR-JAK-STAT signaling triggered by tumor-associated fibroblasts, which suggests that these compounds could potentially overcome the drug resistance caused by the tumor microenvironment. More importantly, compound 15d effectively inhibited the tumor growth in MDA-MB-231 xenograft tumor model. Overall, this work provides valuable leads and novel antitumor mechanisms for the treatment of the SAHA-resistant triple-negative breast cancers.
Novel 7H-pyrrolo[2,3-d]pyrimidine derivatives as potent and orally active STAT6 inhibitors
Nagashima, Shinya,Hondo, Takeshi,Nagata, Hiroshi,Ogiyama, Takashi,Maeda, Jun,Hoshii, Hiroaki,Kontani, Toru,Kuromitsu, Sadao,Ohga, Keiko,Orita, Masaya,Ohno, Kazuki,Moritomo, Ayako,Shiozuka, Koichi,Furutani, Masako,Takeuchi, Makoto,Ohta, Mitsuaki,Tsukamoto, Shin-ichi
experimental part, p. 6926 - 6936 (2009/12/24)
Signal transducers and activators of transcription 6 (STAT6) is an important transcription factor in interleukin (IL)-4 signaling pathway and a key regulator of the type 2 helper T (Th2) cell immune response. Therefore, STAT6 may be an excellent therapeut
