Ketley, Ami published the artcileCDK12 inhibition reduces abnormalities in cells from patients with myotonic dystrophy and in a mouse model, COA of Formula: C30H32ClN7O2, the publication is Science Translational Medicine (2020), 12(541), eaaz2415, database is CAplus and MEDLINE.
Myotonic dystrophy type 1 (DM1) is an RNA-based disease with no current treatment. It is caused by a transcribed CTG repeat expansion within the 3â?untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. Mutant repeat expansion transcripts remain in the nuclei of patientsâ?cells, forming distinct microscopically detectable foci that contribute substantially to the pathophysiol. of the condition. Here, we report small-mol. inhibitors that remove nuclear foci and have beneficial effects in the HSALR mouse model, reducing transgene expression, leading to improvements in myotonia, splicing, and centralized nuclei. Using chemoproteomics in combination with cell-based assays, we identify cyclin-dependent kinase 12 (CDK12) as a druggable target for this condition. CDK12 is a protein elevated in DM1 cell lines and patient muscle biopsies, and our results showed that its inhibition led to reduced expression of repeat expansion RNA. Some of the inhibitors identified in this study are currently the subject of clin. trials for other indications and provide valuable starting points for a drug development program in DM1.
Science Translational Medicine 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 C30H32ClN7O2, COA of Formula: C30H32ClN7O2.
Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem