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PROfound is a prospective, multi-center, randomised, open-label, Phase 3 trial evaluating the efficacy and safety of Lynparza versus enzalutamide or abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on prior treatment with a new hormonal anticancer treatment and have a qualifying tumor mutation in one of 15 genes involved in the homologous recombination repair pathway, among them BRCA 1/2, ATM and CDK12.
PROfound is a prospective, multicentre, randomised, open-label, Phase III trial testing the efficacy and safety of Lynparza versus enzalutamide or abiraterone in patients with mCRPC who have progressed on prior treatment with new hormonal anticancer treatments and have a qualifying tumour mutation in one of 15 genes involved in the HRR pathway, including among them BRCA1/2, ATM and CDK12.
Using a representative member of Syros' suite of oral CDK7 inhibitors, these data show: 200- to 1,200-fold greater selectivity for CDK7 over other members of the CDK family, including CDK2, CDK9 and CDK12. Robust anti-proliferative activity in triple negative breast cancer and ovarian cancer cell lines, which was associated with the induction of apoptosis and cell cycle arrest.
Fann, "Cdk12 and Cdk13 regulate axonal elongation through a common signaling pathway that modulates Cdk5 expression," Experimental Neurology, vol.
The genomic landscape of localised prostate cancer has been well defined, describing putative pathogenic BRCA2 germ line mutations as well as somatic and germ line DNA repair alterations found such as BRCA1, CDK12, FANCA, and RAD51B.
Almost all tumors (96%) were characterized by mutations of the gene encoding TP53 in addition to statistically recurrent mutations in nine other loci, including NF1, BRCA1, BRCA2, RBI, and CDK12, although these were of low prevalence.
Details: PlaneWave Instruments CDK12.5 corrected Dall-Kirkham astrograph with QSI 640ws CCD camera.
Demonstrated 13,000- to 49,000-fold greater selectivity for CDK7 over other CDK family members, including CDK2, CDK9 and CDK12.
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- CDk Activating Kinase
- CDK inhibitor p19INK4d
- CDK inhibitory protein
- CDK-activating kinase
- CDK-activating kinase p42
- Cdk-associated protein phosphatase
- CDK-Interacting Protein
- CDK-interacting protein 1
- CDK-interaction protein 1
- CDK2-associated dual specificity phosphatase
- CDK2-associated dual-specificity phosphatase
- CDK4 gene
- CDK4 gene
- CDK4 inhibitor p16-INK4, INK4a
- CDK4B inhibitor
- CDK5-Binding Protein
- CDK6 inhibitor p18