HLM006474

HLM006474 is a non-selective inhibitor of the transcription factor E2F (IC₅₀ = 29.8 µM for E2F4).¹ It inhibits DNA binding to E2F1, E2F2, and E2F4 in A375 melanoma cells when used at a concentration of 40 µM. HLM006474 (40 µM) decreases protein levels of E2F4 and cyclin D3 and induces apoptosis in A375 cells. It also induces apoptosis in MDA-MB-231, but not MCF-7, cells and inhibits the growth of cancer cells in a panel of 17 lung cancer cell lines (IC₅₀s = 15.5-75.1 µM).^1,2 HLM006474 reduces tumor growth in retinoblastoma-prone Chx10Cre;Rb^fl/fl;p107^-/- mice and in an A375 mouse xenograft model when administered at a dose of 100 mg/kg and 2 mg per mouse, respectively.^3,4

WARNING This product is not for human or veterinary use.

1. Ma, Y., Kurtyaka, C.A., Boyapalle, S., et al. A small-molecule E2F inhibitor blocks growth in a melanoma culture model. Cancer Res. 68(15), 6292-6299 (2008).

2. Kurtyaka, C.A., Chen, L., and Cress, W.D. E2F inhibition synergizes with paclitaxel in lung cancer cell lines. PLoS One 9(5), e96357 (2014).

3. Sangwan, M., McCurdy, S.R., Livne-Bar, I., et al. Established and new mouse models reveal E2f1 and Cdk2 dependency of retinoblastoma, and expose effective strategies to block tumor initiation. Oncogene 31(48), 5019-5028 (2012).

4. Rouaud, F., Hamouda-Tekaya, N., Cerezo, M., et al. E2F1 inhibition mediates cell death of metastatic melanoma. Cell Death Dis. 9(5), 527 (2018).