Most of the compounds have physiologically active properties, and their biological properties are often attributed to the heteroatoms contained in their molecules, and most of these heteroatoms also appear in cyclic structures. A Journal, Article, European Journal of Medicinal Chemistry called Structure-activity relationship study of THZ531 derivatives enables the discovery of BSJ-01-175 as a dual CDK12/13 covalent inhibitor with efficacy in Ewing sarcoma, Author is Jiang, Baishan; Jiang, Jie; Kaltheuner, Ines H.; Iniguez, Amanda Balboni; Anand, Kanchan; Ferguson, Fleur M.; Ficarro, Scott B.; Seong, Bo Kyung Alex; Greifenberg, Ann Katrin; Dust, Sofia; Kwiatkowski, Nicholas P.; Marto, Jarrod A.; Stegmaier, Kimberly; Zhang, Tinghu; Geyer, Matthias; Gray, Nathanael S., which mentions a compound: 882562-40-5, SMILESS is ClC1=NC(C2=CN(C3=C2C=CC=C3)S(=O)(=O)C2=CC=CC=C2)=C(Cl)C=N1, Molecular C18H11Cl2N3O2S, Related Products of 882562-40-5.
Development of inhibitors targeting CDK12/13 is of increasing interest as a potential therapy for cancers as these compounds inhibit transcription of DNA damage response (DDR) genes. We previously described THZ531, a covalent inhibitor with selectivity for CDK12/13. In order to elucidate structure-activity relationship (SAR), we have undertaken a medicinal chem. campaign and established a focused library of THZ531 analogs. Among these analogs, BSJ-01-175 demonstrates exquisite selectivity, potent inhibition of RNA polymerase II phosphorylation, and downregulation of CDK12-targeted genes in cancer cells. A 3.0 Å co-crystal structure with CDK12/CycK provides a structural rational for selective targeting of Cys1039 located in a C-terminal extension from the kinase domain. With moderate pharmacokinetic properties, BSJ-01-175 exhibits efficacy against an Ewing sarcoma tumor growth in a patient-derived xenograft (PDX) mouse model following 10 mg/kg once a day, i.p. administration. Taken together, BSJ-01-175 represents the first selective CDK12/13 covalent inhibitor with in vivo efficacy reported to date.
Although many compounds look similar to this compound(882562-40-5)Related Products of 882562-40-5, numerous studies have shown that this compound(SMILES:ClC1=NC(C2=CN(C3=C2C=CC=C3)S(=O)(=O)C2=CC=CC=C2)=C(Cl)C=N1), has unique advantages. If you want to know more about similar compounds, you can read my other articles.
Reference:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem