CDK9 Degrader

TL12-186 is a multi-kinase PROTAC degrader. TL12-186 recruits the CRBN E3 ubiquitin ligase to target and degrade a variety of distinct kinases, including FLT3, BTK, AURKA, PTK2B, and multiple cyclin-dependent kinases (CDKs). TL12-186 can be used in leukemia-related research.

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 selective CDK9 PROTAC degrader (IC₅₀ = 3 nM; DC₅₀ = 0.89 nM). KI-CDK9d-32 induces CDK9 degradation via the ubiquitin-proteasome pathway to abrogates CDK9 enzymatic and scaffolding functions, downregulates MYC expression and MYC-dependent signaling, represses TNF-alpha signaling pathways activity and pre-rRNA levels. KI-CDK9d-32 disrupts nucleolar homeostasis, blocks cell cycle progression and cellular translation by reducing 4EBP1 phosphorylation, and elicits cancer cell cytotoxicity in a CRBN-dependent manner, while high ABCB1 activity attenuates the efficacy. KI-CDK9d-32 can be used for the research of acute lymphoblastic leukemia, rhabdomyosarcoma, pancreatic adenocarcinoma.

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 is an orally active, selective CDK9 PROTAC degrader with a DC₅₀ of 3.94 nM. PROTAC CDK9 degrader-9 downregulates downstream targets c-Myc and MCL-1. PROTAC CDK9 degrader-9 inhibits the proliferation of breast cancer cells. PROTAC CDK9 degrader-9 can be used for the research of triple-negative breast cancer.

PROTAC CDK9 degrader-2 is a PROTAC degrader targeting CDK9, with an IC₅₀ of 523 nM. PROTAC CDK9 degrader-2 selectively degrades CDK9 via the cereblon-dependent ubiquitin-proteasome pathway and inhibits the proliferation of cancer cells overexpressing CDK9. PROTAC CDK9 degrader-2 can be used for cancer research.

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.

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.

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.

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).

CDK9 degrader-1 is a HyT-type CDK9 degrader that selectively induces protein degradation by recruiting ATG101 (with a DC₅₀ of 0.4073 μM in HCT116 cells). CDK9 degrader-1 recruits ATG101 to initiate the autophagy-lysosome pathway, forming LC3-containing autophagosomes that fuse with lysosomes to degrade CDK9. CDK9 degrader-1 mediates the degradation of Cyclin T1 via the same autophagy-lysosome pathway. CDK9 degrader-1 induces downstream phenotypic effects associated with CDK9 degradation. CDK9 degrader-1 can be used in the research of colorectal cancer (Blue: hydrophobic group; Pnk: CDK9 ligand (HY-50940); Black: linker (HY-N0420)).

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).

PROTAC CDK9 degrader-13 is a selective CDK9 degrader acting via the ubiquitin-proteasome system. PROTAC CDK9 degrader-13 induces apoptosis in acute myeloid leukemia cells. PROTAC CDK9 degrader-13 suppresses tumor growth in vivo and has a defined safety profile. PROTAC CDK9 degrader-13 can be used for the research of acute myeloid leukemia.

PROTAC CDK9 degrader-14 is a CDK9 PROTAC degrader that recruits CRBN. PROTAC CDK9 degrader-14 efficiently degrades CDK9 and inhibits cell proliferation in solid tumors and hematological malignancies. PROTAC CDK9 degrader-14 can be used in research related to solid tumors, hematological malignancies and triple-negative breast cancer.

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))

CDK9/CycT1 degrader-1 is an autophagy-anchored bifunctional degrader that mediates the degradation of the CDK9/cyclin T1 protein complex. CDK9/CycT1 degrader-1 binds both CDK9 and LC3B simultaneously to form a ternary complex, achieving target protein degradation via the autophagy-lysosome pathway. CDK9/CycT1 degrader-1 downregulates the protein levels of Mcl‑1 and c‑Myc and induces apoptosis. PROTAC CDK9/CycT1 Degrader-2 is applicable to cancer-related research.

PROTAC CDK4/6/9 degrader 1 prodrug is an orally active CDK4/CDK6/CDK9 PROTAC degrader prodrug. PROTAC CDK4/6/9 degrader 1 prodrug converts into PROTAC CDK4/6/9 degrader 1 (HY-178452). PROTAC CDK4/6/9 degrader 1 degrades CDK4, CDK6 and CDK9. PROTAC CDK4/6/9 degrader 1 prodrug is applicable to the research of triple-negative breast cancer (prodrug modification moiety: Lauric acid (HY-Y0366); PROTAC moiety: PROTAC CDK4/6/9 degrader 1 (HY-178452)).