SEL120 (SEL120-34, SEL120-34A) is a novel inhibitor of Cyclin-dependent kinase 8 (CDK8) with IC50 values of 4.4 nM and 10.4 nM for CDK8/Cyclin C and CDK19/CyclinC respectively.
Storage Temp
Store at -80°C
Shipped In
Ice chest + Ice pads
Product Description
Information
SEL120 (SEL120-34A) hydrochloride SEL120 (SEL120-34, SEL120-34A) is a novel inhibitor of Cyclin-dependent kinase 8 (CDK8) with IC50 values of 4.4 nM and 10.4 nM for CDK8/Cyclin C and CDK19/CyclinC respectively.
SEL120-34A inhibits kinase activities of CDK8/CycC and CDK19/CycC complexes with an IC50 of 4.4 nM and 10.4 nM, respectively. It does not significantly inhibit other members of the CDK family in a single point inhibition assay, namely CDK1, 2, 4, 6, 5, 7 with the exception of CDK9, however a calculated IC50 1070 nM, indicated an over 200 fold selectivity against this kinase. SEL120-34A inhibits phosphorylation of STAT1 S727 and STAT5 S726 in cancer cells, inhibits mitogen- induced expression of immediate early response (IER) genes and IFN- responsive genes expression in vitro. In a broad panel of cancer cell lines, the compound shows the strongest activity in hematological malignancies, especially in selected acute myeloid leukemia (AML) (GI50 12 nM), acute lymphoblastic leukemia (ALL) and mantle cell lymphoma (MCL) models. SEL120−34A could alter transcriptional programs linked to differentiation of leukemia cells.
In vivo
SEL120-34A has favorable pharmacodynamics to be sufficient to affect expression of CDK8 and CDK19- dependent genes in vivo. SEL120-34A treatment causes specific alterations in interferon- responsive genes and inhibits the proliferation of AML cell lines in vivo. SEL120-34A does not affect normal hematopoiesis. SEL120−34A effectively inhibits tumor growth in subcutaneous responder AML and MCL models when administered orally.
