Product Details of 52096-24-9On November 25, 2020 ,《Discovery of S64315, a Potent and Selective Mcl-1 Inhibitor》 appeared in Journal of Medicinal Chemistry. The author of the article were Szlavik, Zoltan; Csekei, Marton; Paczal, Attila; Szabo, Zoltan B.; Sipos, Szabolcs; Radics, Gabor; Proszenyak, Agnes; Balint, Balazs; Murray, James; Davidson, James; Chen, Ijen; Dokurno, Pawel; Surgenor, Allan E.; Daniels, Zoe Marie; Hubbard, Roderick E.; Le Toumelin-Braizat, Gaetane; Claperon, Audrey; Lysiak-Auvity, Gaelle; Girard, Anne-Marie; Bruno, Alain; Chanrion, Maia; Colland, Frederic; Maragno, Ana-Leticia; Demarles, Didier; Geneste, Olivier; Kotschy, Andras. The article conveys some information:
Myeloid cell leukemia 1 (Mcl-1) has emerged as an attractive target for cancer therapy. It is an antiapoptotic member of the Bcl-2 family of proteins, whose upregulation in human cancers is associated with high tumor grade, poor survival, and resistance to chemotherapy. Here we report the discovery of our clin. candidate S64315, a selective small mol. inhibitor of Mcl-1. Starting from a fragment derived lead compound, we have conducted structure guided optimization that has led to a significant (3 log) improvement of target affinity as well as cellular potency. The presence of hindered rotation along a biaryl axis has conferred high selectivity to the compounds against other members of the Bcl-2 family. During optimization, we have also established predictive PD markers of Mcl-1 inhibition and achieved both efficient in vitro cell killing and tumor regression in Mcl-1 dependent cancer models. The preclin. candidate has drug-like properties that have enabled its development and entry into clin. trials. In addition to this study using 1-Butyl-1H-pyrazole, there are many other studies that have used 1-Butyl-1H-pyrazole(cas: 52096-24-9Product Details of 52096-24-9) was used in this study.
1-Butyl-1H-pyrazole(cas: 52096-24-9) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Product Details of 52096-24-9
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics