So far, in addition to halogen atoms, other non-metallic atoms can become part of the aromatic heterocycle, and the target ring system is still aromatic.Liang, Xuewu; Zang, Jie; Li, Xiaoyang; Tang, Shuai; Huang, Min; Geng, Meiyu; Chou, C. James; Li, Chunpu; Cao, Yichun; Xu, Wenfang; Liu, Hong; Zhang, Yingjie researched the compound: Methyl 3-bromopropanoate( cas:3395-91-3 ).Recommanded Product: 3395-91-3.They published the article 《Discovery of Novel Janus Kinase (JAK) and Histone Deacetylase (HDAC) Dual Inhibitors for the Treatment of Hematological Malignancies》 about this compound( cas:3395-91-3 ) in Journal of Medicinal Chemistry. Keywords: pyrimidinaminopyrazole hydroxamate preparation JAK HDAC inhibitor hematol malignancy treatment; selected pyrimidinaminopyrazole compound pharmacokinetic study bioavailability antitumor efficacy. We’ll tell you more about this compound (cas:3395-91-3).
Concurrent inhibition of Janus kinase (JAK) and histone deacetylase (HDAC) could potentially improve the efficacy of the HDAC inhibitors in the treatment of cancers and resolve the problem of HDAC inhibitor resistance in some tumors. Here, a novel series of pyrimidin-2-amino-pyrazol hydroxamate derivatives as JAK and HDAC dual inhibitors was designed, synthesized, and evaluated, among which I possessed potent and balanced activities against both JAK2 and HDAC6 with half-maximal inhibitory concentration at the nanomolar level. I exhibited improved antiproliferative and proapoptotic activities over SAHA and ruxolitinib in several hematol. cell lines. Remarkably, I exhibited more potent antiproliferation effect than the combination of SAHA and ruxolitinib in HEL cells bearing JAK2V617F mutation. Pharmacokinetic studies in mice showed that I possessed good bioavailability after i.p. administration. Finally, I showed antitumor efficacy with no significant toxicity in a HEL xenograft model. Collectively, the results confirm the therapeutic potential of JAK and HDAC dual inhibitors in hematol. malignancies and provide valuable leads for further structural optimization and antitumor mechanism study.
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Reference:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem