CDK Degrader

(R)-CDK2 degrader 6 is the R-enantiomer of CDK2 degrader 6 (HY-176444), a cereblon-based molecular glue degrader of CDK2 with a DC₅₀ of 27 nM. (R)-CDK2 degrader 6 induces ubiquitination and proteasomal degradation of CDK2 by bridging cereblon and CDK2. (R)-CDK2 degrader 6 is applicable for cancer research.

PROTAC CDK2/4 Degrader-1 is a PROTAC degrader of cyclin-dependent kinase 2 (CDK2) and cyclin-dependent kinase 4 (CDK4). PROTAC CDK2/4 Degrader-1 induces degradation via the ubiquitin-proteasome pathway. PROTAC CDK2/4 Degrader-1 can be used in cancer research.

LL-K9-3 is a selective CDK9-cyclin T1 HyT degrader, with DC₅₀ values of 0.662 μM and 0.589 μM for CDK9 and Cyclin T1, respectively. LL-K9-3 lacks an E3 ligand moiety and induces polyubiquitination and proteasome-mediated synchronous degradation of CDK9 and cyclin T1 via a hydrophobic tag-mediated mechanism. LL-K9-3 downregulates the protein levels of androgen receptor (AR) and c-Myc, and exhibits antiproliferative and pro-apoptotic (apoptosis) activity in prostate cancer cells. LL-K9-3 can be used in studies related to prostate cancer.

LA-CB1 is an Abemaciclib (HY-16297A) derivative that targets CDK4/6 and promotes its degradation via the ubiquitin-proteasome pathway, thereby disrupting the CDK4/6-Cyclin D1-Rb-E2F axis and inducing G0/G1 cell cycle arrest and apoptosis. LA-CB1 exhibits antiproliferative activity against MDA-MB-231 cells, with an IC₅₀ of 0.27 µM, and effectively inhibits epithelial-mesenchymal transition (EMT), cell migration, invasion, and angiogenesis. In highly aggressive models such as triple-negative breast cancer (TNBC), LA-CB1 significantly suppresses tumor growth in a dose-dependent manner. LA-CB1 holds potential for research in the field of breast cancer.

YJ9069 is a CDK12/CDK13 PROTAC degrader. YJ9069 induces proteasome-dependent degradation of CDK12 and CDK13, and inhibits serine 2 phosphorylation of RNA polymerase II (RNA polymerase II). YJ9069 triggers gene length-dependent transcription elongation defects, reduces the expression of DNA damage response genes, and induces DNA damage, cell cycle arrest and apoptosis. YJ9069 inhibits tumor growth in prostate cancer models. YJ9069 can be used for the research of prostate cancer, Ewing sarcoma and breast cancer.

PROTAC CDK2/4/6 Degrader-2 is a CDK2/4/6 PROTAC degrader. PROTAC CDK2/4/6 Degrader-2. PROTAC CDK2/4/6 Degrader-2 can be converted into the prodrug PROTAC CDK2/4/6 Degrader-1 (HY-171826) through a one-step reaction with chloromethyl pivalate. PROTAC CDK2/4/6 Degrader-2 degrades CDK2/4/6 and their complex in malignant melanomas cells. PROTAC CDK2/4/6 Degrader-2 induces cell cycle arrest and cell apoptosis in various cancer cells, in particular for melanomas. PROTAC CDK2/4/6 Degrader-2 can be used for malignant melanomas research.

(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 is a CDK4/CDK6 degrader. LO-3-63 induces proteasome-dependent degradation of CDK4/6 via CUL4^DCAF16-dependent interaction.

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.

WWZ-11-098 is a selective CDK6 PROTAC degrader with DC₅₀ of 2.6 nM. WWZ-11-098 induces degradation of CDK6 in a CRBN-dependent manner, while sparing CDK1, CDK2, CDK4, and CDK9. WWZ-11-098 induces apoptosis, G1-S cell cycle arrest and shows anti-proliferative activity in cancer cells. WWZ-11-098 exhibits antitumor efficacy in a xenograft model without signs of toxicity. WWZ-11-098 can be used for the research of leukemia.

PROTAC CDK6 Degrader 1 (compound 48a) is a potent and selective PROTAC CDK6 degrader with a DC₅₀ of 0.037 μM. PROTAC CDK6 Degrader 1 exhibits selectivity over CDK4 (DC₅₀ > 10 μM). PROTAC CDK6 Degrader 1 induces G0/G1 cell-cycle arrest and apoptosis through inhibition of CDK6 downstream signaling. PROTAC CDK6 Degrader 1 reduces tumor burden and CDK6 levels in a MOLM-14 xenograft mouse model. PROTAC CDK6 Degrader 1 can be used for CDK6-driven cancers research, such as acute myeloid leukemia (AML).

PROTAC FLT3/CDKs degrader-1 is a PROTAC degrader targeting CDKs and FLT3. PROTAC FLT3/CDKs degrader-1 degrades CDK2, CDK4, CDK6, CDK9 and FLT3 proteins via a ubiquitin-proteasome-dependent bivalent mechanism, with a DC₅₀ of 18.73 nM against CDK2. PROTAC FLT3/CDKs degrader-1 promotes myeloid cell differentiation. PROTAC FLT3/CDKs degrader-1 inhibits leukemia cell proliferation. PROTAC FLT3/CDKs degrader-1 can be used for the research of acute myeloid leukemia.

TMX-2138 is a CDK PROTAC degrader, with IC₅₀ values against different targets as follows: CDK1 (IC₅₀ = 8.7 nM), CDK2 (IC₅₀ = 10.9 nM), CDK5 (IC₅₀ = 7.0 nM), CDK4 (IC₅₀ = 901.0 nM), CDK6 (IC₅₀ = 465.0 nM), CDK7 (IC₅₀ = 286.0 nM), and CDK9 (IC₅₀ = 25.7 nM). TMX-2138 promotes the ubiquitination of CDK and induces its degradation via the proteasomal pathway. TMX-2138 can be used in ovarian cancer research.

DN1679 is a potent, selective and orally active CRBN-dependent CDK12/13 PROTAC dual degrader. DN1679 shows DC₅₀ of 8.8/9.8 nM (MDA-MB-231), 5.1/6.4 nM (MDA-MB-157) and 17.2/15.8 nM (MDA-MB-468) for CDK12/13. DN1679 can downregulate DNA damage response gene mRNA levels, such as ATM, ATR, BRCA1 and RAD51. DN1679 demonstrates a potent synergistic anti-tumor effect companied with Olaparib (HY-10162). DN1679 can be used for research of triple-negative breast cance.

CDK6 ligand-3 is a PROTAC target protein ligand (Ligands for Target Protein for PROTACs) that targets CDK6. CDK6 ligand-3 can be used to synthesize the PROTAC JHK-02-108-2 (HY-184910).

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.

CDK9 degrader-2 is a bifunctional degrader of ATTEC (Autophagy-Tethering Compound) that degrades the CDK9/cyclin T1 complex. CDK9 degrader-2 forms a ternary complex with CDK9 and LC3B, and achieves degradation through the autophagy-lysosome pathway, a process independent of the ubiquitin-proteasome system. CDK9 degrader-2 downregulates the expression of Mcl-1 and c-Myc proteins, induces apoptosis, and exhibits antitumor activity in in vivo MV4-11 xenograft models. CDK9 degrader-2 can be used for leukemia research.

CP-07 is a selective flavonoid-based PROTAC degrader that targets and degrades CDK9. CP-07 exhibits an IC₅₀ of 3.3 nM against CDK9/cyclin T1, and induces CDK9 degradation in a concentration-dependent manner in 22RV1 cells with a DC₅₀ of 43 nM. CP-07 rapidly triggers ligand-dependent and proteasome-dependent degradation of CDK9. CP-07 can be applied in prostate cancer-related research.

PROTAC CDK9 degrader-11 is an orally active, selective CDK9 PROTAC degrader with a DC₅₀ of 1.09 nM. PROTAC CDK9 degrader-11 recruits CRBN to form a ternary complex and degrades CDK9 via the ubiquitin-proteasome pathway, thereby inhibiting RNA polymerase II phosphorylation and downregulating the expression of anti-apoptotic and pro-oncogenic genes, ultimately inducing apoptosis. PROTAC CDK9 degrader-11 is suitable for research on small-cell lung cancer (SCLC).