Category: amides-buliding-blocks. I found the field of Pharmacology & Pharmacy very interesting. Saw the article Structure-Based Discovery of SD-36 as a Potent, Selective, and Efficacious PROTAC Degrader of STAT3 Protein published in 2019.0, Reprint Addresses Wang, SM (corresponding author), Univ Michigan, Rogel Canc Ctr, Ann Arbor, MI 48109 USA.; Wang, SM (corresponding author), Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.; Wang, SM (corresponding author), Univ Michigan, Dept Pharmacol, Med Sch, Ann Arbor, MI 48109 USA.; Wang, SM (corresponding author), Univ Michigan, Coll Pharm, Med Chem, 428 Church St, Ann Arbor, MI 48109 USA.. The CAS is 91-00-9. Through research, I have a further understanding and discovery of Diphenylmethanamine.
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor and an attractive therapeutic target for cancer and other human diseases. Despite 20 years of persistent research efforts, targeting STAT3 has been very challenging. We report herein the structure-based discovery of potent small-molecule STAT3 degraders based upon the proteolysis targeting chimera (PROTAC) concept. We first designed SI-109 as a potent, small-molecule inhibitor of the STAT3 SH2 domain. Employing ligands for cereblon/cullin 4A E3 ligase and SI-109, we obtained a series of potent PROTAC STAT3 degraders, exemplified by SD-36. SD-36 induces rapid STAT3 degradation at low nanomolar concentrations in cells and fails to degrade other STAT proteins. SD-36 achieves nanomolar cell growth inhibitory activity in leukemia and lymphoma cell lines with high levels of phosphorylated STAT3. A single dose of SD-36 results in complete STAT3 protein degradation in xenograft tumor tissue and normal mouse tissues. SD-36 achieves complete and long-lasting tumor regression in the Molm-16 xenograft tumor model at well-tolerated dose-schedules. SD-36 is a potent, selective, and efficacious STAT3 degrader.
About Diphenylmethanamine, If you have any questions, you can contact Zhou, HB; Bai, LC; Xu, RQ; Zhao, YJ; Chen, JY; McEachern, D; Chinnaswamy, K; Wen, B; Dai, LP; Kumar, P; Yang, CY; Liu, ZM; Wang, M; Liu, L; Meagher, JL; Yi, H; Sun, DX; Stuckey, JA; Wang, SM or concate me.. Category: amides-buliding-blocks
Reference:
Amide – Wikipedia,
,Amide – an overview | ScienceDirect Topics