Moreover, we showed that the cell-cycle arrest was accompanied by down-regulation of CCNA1, CCND1, CCND2, CCNH, CDKN1B, MCM2, ORC6L, and WEE1 and upregulation of CDC7, CDK6, CDK7
, E2F3, and RB1.
Abbreviations: ARG, arctigenin; GSH, glutathione; [G.sub.0]/[G.sub.1] , Gap 0/Gap 1; NPAT, nuclear protein of the ataxia telangiectasia locus; CDK2, cyclin-dependent kinase 2; CDK7, cyclin-dependent kinase 7: akt-1, alpha serine/threonine-protein kinase.
CDK7, cyclin-dependent kinase 7; akt-1, alpha serine/threonine-protein kin
New preclinical data on SY-5609, a selective oral CDK7 inhibitor, demonstrate broad anti-tumor activity in preclinical models of triple-negative breast cancer and ovarian cancer.
Demonstrated 13,000- to 49,000-fold greater selectivity for CDK7 over other CDK family members, including CDK2, CDK9 and CDK12.
agonist in a Phase 2 clinical trial for genomically defined subsets of patients with acute myeloid leukemia and myelodysplastic syndrome, and SY-1365, a selective CDK7
inhibitor in a Phase 1 clinical trial for patients with ovarian and breast cancers.
PD assays used to establish proof-of-mechanism included a CDK7
occupancy assay to evaluate SY-1365 binding and a custom gene expression assay to evaluate downstream transcriptional changes in patients.
M2 PHARMA-May 16, 2017-First Patient Dosed in Phase 1 Clinical Trial of Syros' SY-1365 Selective CDK7
Inhibitor in Patients with Advanced Solid Tumors
M2 PHARMA-April 11, 2017-US FDA Accepts Syros IND to Advance Its SY-1365 Selective CDK7
Inhibitor into Phase 1 Clinical Trial