Early 2 Factor (E2F) Inhibitor

HLM006474 is a pan E2F inhibitor, which inhibits E2F4 DNA-binding with an IC₅₀ of 29.8 μM in A375 cells.

LL-K8-22 is a dual degrader of CDK8 and cyclin C HyT, with DC₅₀ values of 2.52 μM and 2.64 μM, respectively. LL-K8-22 inhibits phosphorylation of STAT1 Ser 727, phosphorylation of the C-terminal domain Ser 2/5 of RNA polymerase II, and phosphorylation of Rb. LL-K8-22 represses E2F- and MYC-driven transcriptional programs and exhibits antiproliferative effects. LL-K8-22 synchronously induces proteasome-dependent selective degradation of CDK8 and cyclin C without degrading CDK19, other CDK family members, or other cyclins. LL-K8-22 can be used in the research of triple-negative breast cancer and colon cancer.

Q901 (CDK7-IN-21) is a selective covalent ATP-competitive CDK7 inhibitor with an IC₅₀ value of 10 nM against human CDK7. Q901 inhibits MYC/E2F-dependent oncogenic transcription, the RNAPII transition from initiation to elongation, and DNA damage repair, stabilizes TOP1-DNA protein crosslinks, and induces DNA damage. Q901 sensitizes tumors to topoisomerase I inhibitors and TOP1 inhibitor-based antibody-drug conjugates. Q901 shows additive or synergistic tumor growth inhibition in solid tumor models in combination with PARP inhibitors, SERDs, ER PROTAC degraders, or anti-PD-1 antibodies. Q901 can be used for research on cancers such as ovarian cancer and lung cancer.

Q901 TFA (CDK7-IN-21 TFA) is a selective covalent ATP-competitive CDK7 inhibitor with an IC₅₀ value of 10 nM against human CDK7. Q901 TFA inhibits MYC/E2F-dependent oncogenic transcription, the RNAPII transition from initiation to elongation, and DNA damage repair, stabilizes TOP1-DNA protein crosslinks, and induces DNA damage. Q901 TFA sensitizes tumors to topoisomerase I inhibitors and TOP1 inhibitor-based antibody-drug conjugates. Q901 TFA shows additive or synergistic tumor growth inhibition in solid tumor models in combination with PARP inhibitors, SERDs, ER PROTAC degraders, or anti-PD-1 antibodies. Q901 TFA can be used for research on cancers such as ovarian cancer and lung cancer.

P-SiaFNEtoc is a Sialyltransferase inhibitor that blocks sialic acid capping of glycans. P-SiaFNEtoc forms CMP-SiaFNEtoc, reduces endogenous CMP-Neu5Ac, feedback-inhibits GNE, and depletes sialylation on N-glycans and O-GalNAc glycans. P-SiaFNEtoc decreases cell surface sialoglycan levels, VEGF and DKK-1 secretion, Tn antigen levels, and cell cycle checkpoint/E2F target gene expression, while inducing p27/Kip1 and fucosylation. P-SiaFNEtoc can be used in research on prostate cancer, and melanoma.

MRT00033659 is a potent broad-spectrum kinase inhibitor of CK1 (IC₅₀=0.9 μM for CK1δ) and CHK1 (IC₅₀=0.23 μM). MRT00033659, a pyrazolo-pyridine analogue, induces p53 pathway activation and E2F-1 destabilisation.

Edifoligide is a decoy oligonucleotide that binds to and inhibits E2F transcription factors and thus may prevent neointimal hyperplasia and vein graft failure

Ly101-4B is an apoptosis inducer and multi-target inhibitor with antiproliferative, antitumor and cycytotoxic effects. Ly101-4B reduces HSF1 expression, inhibits microRNA-214 synthesis, downregulates HSP27, HSP70 and HSP90 expression, while suppressing E2F-dependent transcriptional activity and downregulating its target genes. Ly101-4B induces caspase 3/7-mediated apoptosis by reducing DNA synthesis, inhibiting the cell cycle and G1/S phase transition, without affecting RNA synthesis or inducing necrosis. Ly101-4B is selective for pancreatic ductal adenocarcinoma cells with different genotypes and varying degrees of E2F dependence. Ly101-4B can be used in research related to epithelial ovarian cancer and pancreatic ductal adenocarcinoma.

Edifoligide sodium is a decoy oligonucleotide that binds to and inhibits E2F transcription factors and thus may prevent neointimal hyperplasia and vein graft failure

JR4-187 is an orally active, copper-dependent anticancer agent. JR4-187 downregulates genes involved in oxidative phosphorylation, MYC targets and E2F targets in cancer cells, while upregulates genes involved in the TNF-α signaling pathway, p53 pathway and KRAS signaling pathway, and downregulates CTR1 protein. JR4-187 induces ROS production, apoptosis, copper-dependent cytotoxicity, and exhibits selective cytotoxicity against KRAS-mutant cancer cells. JR4-187 is well tolerated in mouse models of pancreatic cancer. JR4-187 can be used in research related to cancers such as pancreatic ductal adenocarcinoma, colon cancer and rectal cancer.

JAS239 is a blood-brain barrier-permeable ChoK inhibitor. JAS239 inhibits phosphocholine synthesis and reduces the expression level of E2F1 protein. JAS239 exhibits near-infrared fluorescence properties. JAS239 exerts anti-tumor activity against glioblastoma. JAS239 can be used in studies related to glioblastoma.