CDK Degrader

dCeMM2 (Compound 2) is a molecular glue-type degrader that targets cyclin K. dCeMM2 induces ubiquitination and degradation of cyclin K by prompting an interaction of CDK12-cyclin K with a CRL4B ligase complex.

HQ005 is a potent CCNK degrader with an DC₅₀ value of 0.041 µM. HQ005 is a molecular-glue degrader that mediates interactions between target proteins and components of the ubiquitin-proteasome system to cause selective protein degradation.

dCeMM4 (Compound 5) is a molecular glue degrader. dCeMM4 induces ubiquitination and degradation of cyclin K by prompting an interaction of CDK12-cyclin K with a CRL4B ligase complex.

CDK2 degrader 2 (Compound I-10) is a PROTAC degrader for CDK2 that degrades CDK2 in MKN1 cell with a DC₅₀ <100 nM.

ZLY025 is a potent and orally active CCNK molecular glue degrader with an DC₅₀ of 42.7 nM. ZLY025 exhibits broad-spectrum antiproliferative activity against various tumor cells with IC₅₀ values ranging from 0.08 to 2.45 μM. ZLY025 can induce cells apoptosis and G1 phase arrest. ZLY025 can be used for the research of cancer, such as lung cancer.

Cyclin K degrader 1 (compound 40) is an AT7519 (HY-50940) based Cyclin K degrader with DC₅₀ of 21 nM. Cyclin K degrader 1 has an affinity for cyclin K that is ~500-fold higher than its affinity for CDK12.

LL-K9-3 is a potent small-molecule degrader of CDK9-cyclin T1. LL-K9-3 has anti-proliferative and pro-apoptotic activities and suppresses downstream signaling of CDK9 and AR. Moreover, LL-K9-3 inhibits AR and Myc-driven oncogenic transcriptional programs.

(S)-CDK2 degrader 6 (Compound 8) is the S-enantiomer of CDK2 degrader 6 (HY-176444). (S)-CDK2 degrader 6 is a selective CDK2 molecular glue degrader with a DC₅₀ of 166.7 nM in 24 h. (S)-CDK2 degrader 6 can be used for breast cancer research.

LO-3-63, a Ribociclib (HY-15777) analog bearing a truncated fumaramide handle, is a PROTAC-like CDK4/6 degrader. LO-3-63 induces CUL4^DCAF16-dependent degradation of CDK4/6 in cells.

PROTAC CDK2 Degrader-1 (Compound 41) is a PROTAC degrader for cyclin-dependent kinase 2 (CDK2). PROTAC CDK2 Degrader-1 inhibits the phosphorylation of RB protein in CDK2 dependent cell line OVCAR3 with an IC₅₀ of 100-500 nM.

DS17 is a molecular glue that acts as a potent degrader of cyclin K, with an EC₅₀ of 13 nM. DS17 plays an important role in cancer research.

Anticancer agent 302 (Example 1) is an anticancer agent. Anticancer agent 302 has a DC₅₀ value of 199 nM for Cyclin E1 and an IC₅₀ value of 133 nM for pRB. Anticancer agent 302 can be used for tumor research.

PROTAC CDK9 degrader-11 (Compound C3) is an orally active PROTAC degrader for CDK9 with DC₅₀ of 1.09 nM. PROTAC CDK9 degrader-11 exhibits cytotoxicity in multi small cell lung cancer cell with IC₅₀ of nanomolar levels. PROTAC CDK9 degrader-11 arrests cell cycle at G0/G1 phase, inhibits the cell invasion in DMS114 and DMS53 cell. PROTAC CDK9 degrader-11 exhibits antitumor efficacy in NCI-H446 xenograft mouse models.(Pink: ligand for target protein CDK9 ligand 3 (HY-170979); Black: linker; Blue: ligand for E3 ligase Cereblon E3 ligase Ligand 56 (HY-W247437))

PROTAC FLT3/CDK9 degrader-1 is a potent FLT3 and CDK9 dual PROTAC degrader. PROTAC FLT3/CDK9 degrader-1 induces apoptosis and effective degradation of target proteins FLT3 and CDK9. PROTAC FLT3/CDK9 degrader-1 has the potential for the research of FLT3-ITD mutated AML.

CDK2 degrader 8 (Compound1) is a CDK2 degrader. CDK2 degrader 8 shows potential anti-tumor activity by targeting CDK2. CDK2 degrader 8 can be used for the study of solid tumors (breast cancer, triple negative breast cancer, ovarian serous cystadenocarcinoma) and liquid tumors (diffuse large B-cell lymphoma, acute myelogenous leukemia) associated with abnormal CDK2 function.

FLT3/CDKs ligand-1 (Compound 14) is a ligand for target protein, which promotes the degradation of cyclin-dependent kinase (CDK) and the FMS-like tyrosine kinase 3 (FLT3), inhibits FLT3/CDK related proliferations and survivals of leukemia cells. LT3/CDKs ligand-1 can be used for synthesis of PROTAC FLT3/CDKs degrader-1 (HY-161708).

CCNE1 degrader-1 (I-2) is a degrader targeting CCNE1. CCNE1 degrader-1 can be used in cancer-related research.

CDK12 ligand-3 is a molecular glucose degrading agent that targets the CDK12 protein (DC₅₀ = 35 nM). CDK12 ligand-3 degrades CDK12, CDK13 and their regulatory subunit Cyclin K in a concentration dependent manner, and inhibits RNA polymerase II CTD (Ser2) phosphorylation. CDK12 ligand-3 exhibits potent anti proliferative activity against Jurkat cells. CDK12 ligand-3 can be used for research on cancers such as leukemia.

SST0116CL1 is a HSP90 inhibitor (IC₅₀: 0.21 μM). SST0116CL1 binds to the ATP binding pocket of Hsp90, and interferes with Hsp90 chaperone function thus resulting in client protein (EGFR, CDK4 and AKT) degradation. SST0116CL1 induces degradation of Her2 in BT-474 cell (IC₅₀: 0.2 μM). SST0116CL1 has antiproliferative activity and inhibits tumor growth. SST0116CL1 can be used for the study of leukemia, gastric and ovarian carcinoma.

(R)-PROTAC CDK9 ligand-1 (Compound 19.4) is a CDK9-targeting degrader that can be used to synthesize PROTAC with antitumor activity.