NCGC00244536 (KDM4B Inhibitor B3) is a potent KDM4B inhibitor (IC50: 10 nM).

KDM4B:10 nM

NCGC00244536 significantly suppresses the growth of AR-positive cell lines such as LNCaP and VCaP, demonstrating inhibitory concentration values (IC50s) below one micromolar, while effectively eliminating androgen-induced LNCaP cell proliferation. It exhibits strong preference for rapidly proliferating AR-negative PC3 cells with a strikingly low IC50 of 40 nM, demonstrating greater than 100-fold selectivity compared to immortalized prostate epithelial cell lines PrEC1 and PrEC4. Additionally, NCGC00244536 effectively restricts the expansion of various other cancer cell lines, including breast cancer cell lines MDA-MB2 and MCF-7, showcasing its inhibitory potential across a broad spectrum of cancer types with IC50s in the micromolar range.

Treatment with NCGC00244536 significantly inhibits tumor growth without causing major toxicity in animals, which appear normal. Tumors treated with NCGC00244536 show a substantial increase in cell apoptosis, necrosis, and fibrosis.

LNCaP cells are treated with 0.1, 0.2, 1, 2.5, 5, 20 μM of NCGC00244536. Cell viability is measured using the MTT assay.

For the xenograft animal model, PC3 cell suspension is injected into 4-6 weeks old severe combined immunodeficient (SCID) mice. When tumors become palpable, animals are randomly grouped for drug treatment. Alzet osmotic minipump containing NCGC00244536 (20 mg/kg)is subcutaneously inserted into each animal, which allowed continuous drug delivery to the tumor site for up to 5 days. Tumor volume is recorded every other days and calculated by using the ellipsoid formula.