Shyamsunder, Pavithra published the artcileTHZ531 Induces a State of BRCAness in Multiple Myeloma Cells: Synthetic Lethality with Combination Treatment of THZ 531 with DNA Repair Inhibitors, SDS of cas: 1702809-17-3, the publication is International Journal of Molecular Sciences (2022), 23(3), 1207, database is CAplus and MEDLINE.
Multiple myeloma (MM) is a hematol. disease marked by abnormal growth of B cells in bone marrow. Inherent chromosomal instability and DNA damage are major hallmarks of MM, which implicates an aberrant DNA repair mechanism. Studies have implicated a role for CDK12 in the control of expression of DNA damage response genes. In this study, we examined the effect of a small mol. inhibitor of CDK12-THZ531 on MM cells. Treatment of MM cells with THZ531 led to heightened cell death accompanied by an extensive effect on gene expression changes. In particular, we observed downregulation of genes involved in DNA repair pathways. With this insight, we extended our study to identify synthetic lethal mechanisms that could be exploited for the treatment of MM cells. Combination of THZ531 with either DNA-PK inhibitor (KU-0060648) or PARP inhibitor (Olaparib) led to synergistic cell death. In addition, combination treatment of THZ531 with Olaparib significantly reduced tumor burden in animal models. Our findings suggest that using a CDK12 inhibitor in combination with other DNA repair inhibitors may establish an effective therapeutic regimen to benefit myeloma patients.
International Journal of Molecular Sciences published new progress about 1702809-17-3. 1702809-17-3 belongs to piperidines, auxiliary class Cell Cycle,CDK, name is (R,E)-N-(4-(3-((5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)piperidine-1-carbonyl)phenyl)-4-(dimethylamino)but-2-enamide, and the molecular formula is C15H14O3, SDS of cas: 1702809-17-3.
Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem