ser2

KB-0742 dihydrochloride is a potent, selective, and orally administered inhibitor of CDK9.

(D-Ser2)-Leu-Enkephalin-Thr is a delta selective agent of opioid receptor and shows analgesic effects.

[pSer2, pSer5, pSer7]-CTD (TFA) is a phosphorylated polypeptide at ser2, ser5, and ser7 of RNA polymerase II carboxyl terminus (CTD) and a substrate for CDK7 (cyclin-dependent protein kinase).

[pSer2, pSer5, pSer7]-CTD is a substrate for CDK7(cyclin-dependent protein kinase), a phosphorylated polypeptide at ser2, ser5, and ser7 of RNA polymerase II carboxyl terminus (CTD).

CDK12/13-IN-3 (Compound 12b) is an orally active CDK inhibitor targeting CDK12 and CDK13, with IC50 values of 107.4 nM and 79.4 nM, respectively. This compound inhibits the phosphorylation of Ser2 on the CTD of RNA polymerase II, induces DNA damage, and downregulates the gene expression involved in the DNA damage response (DDR). CDK12/13-IN-3 exhibits antiproliferative effects against various cancer cells with nanomolar IC50 values. In mouse models, it demonstrates antitumor activity, favorable pharmacokinetic properties, and an oral bioavailability of 53.6%.

CDK9-IN-37 (Compound 24) is a CDK9 inhibitor with high selectivity, demonstrating an EC50 of 5.5 nM and minimal inhibition of other CDK subtypes. It shows significant antiproliferative activity against acute myeloid leukemia cells MOLM-13, with an IC50 of 0.034 μM. CDK9-IN-37 suppresses CDK9 signaling, reducing RNAP II CTD (Ser2) phosphorylation, downregulating the anti-apoptotic protein McI-1, inducing apoptosis, and causing cell cycle arrest at the G2/M phase. This compound is applicable in the research of acute myeloid leukemia (AML).

CDK9-IN-33 (compound C35) is a potent, selective, and orally bioavailable CDK9 inhibitor with IC50 values of 17.44 nM for CDK9, 160 nM for CDK7, 316.30 nM for CDK2, 1771.00 nM for CDK4, and >10000 nM for CDK6. This compound induces apoptosis (cell apoptosis) and reduces the protein expression of RPB1 CTD Ser2, RPB1, and MCL1, exhibiting antitumor activity.

AZ5576 racemate is a racemic mixture of AZ5576 isomers. AZ5576 is a potent, highly selective, and orally bioavailable inhibitor of Cdk9 that inhibits Cdk9 enzyme activity with an IC50 <5nM and decreases phosphorlyation of Ser2-RNAPII in cells with an IC50 of 96nM. In the MLL-fusion containing acute myeloid leukemia (AML) line, MV411, short-term treatment with AZ5576 led to a rapid dose-dependent decrease in pSer2-RNAPII with concomitant loss of Mcl1 mRNA and protein, resulting in the cleavage and activation of caspase 3 and loss of cell viability.

CDK9-Cyclin T1 PPI-IN-1 (Compound B19) is a selective inhibitor of the CDK9-Cyclin T1 protein-protein interaction (PPI), suppressing cell proliferation in TNBC MDA-MB-231 cells with an IC50 of 0.044 μM and inducing apoptosis. This compound diminishes CDK9 transcriptional activity and downregulates phosphorylation of RNA Pol II CTD ser2. In vivo, CDK9-Cyclin T1 PPI-IN-1 effectively impedes tumor growth in a TNBC 4T1 mouse model [1].