CDK9 Degrader

PROTAC CDK2/9 Degrader-1 (Compound F3) is a potent dual degrader for CDK2 (DC₅₀=62 nM) and CDK9 (DC₅₀=33 nM). PROTAC CDK2/9 Degrader-1 suppresses prostate cancer PC-3 cell proliferation (IC₅₀=0.12 µM) by effectively blocking the cell cycle in S and G2/M phases. PROTAC CDK2/9 Degrader-1 is a PROTAC by tethering CDK inhibitor with Cereblon ligand.

KI-CDK9d-32 is a highly selective and potent CDK9 PROTAC degrader (DC₅₀: 0.89 nM). KI-CDK9d-32 promotes the ubiquitination and degradation of CDK9. KI-CDK9d-32 inhibits the MYC pathway and disrupts nucleolar homeostasis. KI-CDK9d-32 exhibits anticancer activity against acute lymphoblastic leukemia and pancreatic cancer.

BSJ-5-63 is a potent CDK12, CDK7, CDK9 PROTAC degrader. BSJ-5-63 BSJ-5-63 decreases the protein expression of CDK12, CDK7, CDK9, RNAPII, Cyclin K. BSJ-5-63 decreases the mRNA expression of BRCA1, BRCA2. BSJ-5-63 shows anticancer activity and has the potential for the research of prostate cancer.

PROTAC CDK9 degrader-9 (compound 29) is a highly selective and efficient CDK9 degrader based on PROTAC technology. PROTAC CDK9 degrader-9 can be used in anti-cancer research.

dCDK9-202 a potent CDK9 PROTAC degrader with an DC₅₀ value of 3.5 nM. dCDK9-202 exhibits broad-spectrum anti-tumor activity and extensively disrupts the oncogenic transcriptome. dCDK9-202 can activate Caspase-3/7, increase the level of cleaved PARP, and directly induce apoptosis of tumor cells. dCDK9-202 effectively inhibits TC-71 tumor growth without any signs of toxicity in mice. dCDK9-202 can be used for the study of EGFR-driven cancers such as sarcoma (Pink: CDK9 ligand (HY-178862); Blue: CRBN ligand (HY-W248665); Black: Linker (HY-N8015)).

PROTAC CDK9 degrader-4 is a selective PROTAC CDK9 degrader. PROTAC CDK9 degrader-4 exhibits antiproliferative, pro-apoptotic and in vivo tumor growth inhibitory activities. PROTAC CDK9 degrader-4 can be used for the research of triple-negative breast cancer.

TMX-2138 is a CDKs PROTAC degrader, with IC₅₀s of 8.7 nM, 10.9 nM, 7.0 nM and 25.7 nM for CDK1/cyclinB, CDK2/cyclinA, CDK5/p25 and CDK9/cyclinT1, respectively. TMX-2138 promotes ubiquitination and degradation of CDKs. TMX-2138 can be used for the research of ovarian cancer.

CP-07 is a potent and selective PROTACCDK9 degrader (DC₅₀: 43 nM). CP-07 inhibits 22RV1 cell proliferation (IC₅₀: 62 nM) and colony formation by down-regulating Mcl-1 and c-Myc. CP-07 inhibits 22RV1 xenograft tumor growth. CP-07 can be used for research of prostate cancer.

CDK9 degrader-1 (Compound AZ-9) is a selective CDK9 degrader (DC₅₀: 0.4073 µM). CDK9 degrader-1 recruits ATG101 to initiate the autophagy-lysosome pathway and forms autophagosomes by recruiting LC3, which then fuses with lysosomes to degrade CDK9 and its partner protein Cyclin T1 (DC₅₀: 1.215 µM). CDK9 degrader-1 induces caspase 3-mediated apoptosis. CDK9 degrader-1 has antitumor activity in a mouse HCT116 xenograft model.

CDK9 autophagic degrader 1 (Compound 28) is a ATTEC degrader that can be used to degrade CDK9 and also affects the levels of the associated Cyclin T1. CDK9 autophagic degrader 1 shows over 80% CDK9 inhibition rate at 100 nM. ( Pink: LC3B ligand (HY-168897); Black: linker (HY-W017758); Blue: target protein ligand (HY-10008); linker + target protein ligand (HY-168898))

PROTAC CDK4/6/9 degrader 2 (Compound P4) is a CDK4/6/9 PROTAC prodrug with oral activity and low toxicity. PROTAC CDK4/6/9 degrader 2 can significantly inhibit tumor growth and suppress tumor lung metastasis. PROTAC CDK4/6/9 degrader 2 can be used in the research of cancer such as breast cancer. (Pink: CDK4/6/9 Ligand (HY-168440); Blue: CRBN Ligand (HY-178517); Black: Linker (HY-178512))

PROTAC CDK9 degrader-12 is a selective CDK9 PROTAC degrader with a DC₅₀ of 23 nM. PROTAC CDK9 degrader-12 induces proteasome-dependent degradation of CDK9, blocks CDK9-mediated HIV-1 transcriptional elongation, and reduces HIV-1 RNA synthesis. PROTAC CDK9 degrader-12 is applicable to research related to HIV-1 infection.

PROTAC CDK4/6/9 degrader 1 is a CDK4/6/9 PROTAC degrader. PROTAC CDK4/6/9 degrader 1 degrades CDK4, CDK6, and CDK9 in TNBC cells and inhibits TNBC cell proliferation. PROTAC CDK4/6/9 degrader 1 induces G1 phase arrest, promotes apoptosis, and suppresses cell migration and invasion in TNBC cells. PROTAC CDK4/6/9 degrader 1 can be used for the study of triple-negative breast cancer (TNBC). (Pink: CDK4/6/9 ligand (HY-168440), Blue: CRBN Ligand (HY-14658), Black: Linker (HY-178512), E3 ligase ligand-linker conjugate (HY-178515)).

Cyclin K degrader 2 is a molecular glucose degrading agent that targets the cyclin K protein. Cyclin K degrader 2 has inhibitory activity against CDK1 and CDK9. Cyclin K degrader 2 causes a decrease in RNA polymerase II Ser2 phosphorylation levels, downregulation of DNA damage response gene expression, accumulation of DNA damage, G1 phase arrest of the cell cycle, and apoptosis. Cyclin K degrader 2 can be used for cancer research.