HDAC-IN-45

HDAC-IN-45 (Compound 14) is a small molecule HDAC inhibitor and has anticancer activity, also can forms a hydrogenbond with residue Y303. HDAC-IN-45 (Compound 14) has substantial inhibitory effects towards HDAC1, 2 and 3 isoforms with IC50 values of 0.108, 0.585 and 0.563 μM respectively[1].

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> HDAC

Signaling Pathways >> Epigenetics >> HDAC

HDAC1:0.108 μM (IC50)

HDAC2:0.585 μM (IC50)

HDAC3:0.563 μM μM (IC50)

HDAC6:﹥10 μM (IC50)

HDAC8:6.81 μM (IC50)

HDAC-IN-45 (Compound 14) suppresses the growth of triple-negative breast cancer cells MDA-MB-231 (IC50 = 1.48 μM), MDA-MB-468 (IC50= 0.65 μM), and liver cancer cells HepG2 (IC50= 2.44 μM). HDAC-IN-45 has equally virulent in the HDAC-sensitive cell lines (YCC11) and -resistant gastric cell lines (YCC3/7) and overcome HDACi resistance. HDAC-IN-45 has a high toxicity (IC50= 0.33 μM) in three leukemic cell lines, K-562, KG-1 and THP-1. HDAC-IN-45 (Compound 14) has substantial inhibitory effects towards HDAC1, 2 and 3 isoforms with IC50 values of 0.108, 0.585 and 0.563 μM respectively. HDAC-IN-45 (Compound 14) can elevate acetylation level of histone H3 and expression of p21. HDAC-IN-45 (Compound 14) exerts a dose-dependent upregulation of ac-H3K9 in MDA-MB-231 cells, triggers cell cycle arrest in G1 phase. HDAC-IN-45 (Compound 14) exhibits a potent antitumor efficacy in xenograft mouse model[1]. Cell Proliferation Assay[1] Cell Line: Triple-negative breast cancer cells; liver cancer cells; YCC11 and YCC3/7 Concentration: a series of concentration Incubation Time: 72 h Result: Inhibited the cell growth viability of HepG2 and triple-negative breast cancer cells. Cell Cytotoxicity Assay[1] Cell Line: Three leukemic cell lines (K-562, KG-1 and THP-1); YCC3/7 and YCC11 cell lines Concentration: a series of concentration Incubation Time: 72 h Result: Showed a potent anti-cancer effect, exhibited high sensitivities and strong toxicities with IC50 values below micromolar in leukemic cell lines. Western Blot Analysis[1] Cell Line: MDA-MB-231 cells Concentration: 2 µM Incubation Time: 24 h Result: Elevated acetylation level of histone H3 and expression of p21. Cell Cycle Analysis[1] Cell Line: MDA-MB-231cells Concentration: 4 µM Incubation Time: 24 h Result: Arrested cell cycle in G1 and trigger apoptosis.

HDAC-IN-45 (Compound 14) (25 mg/kg or 50mg/kg; i.p.; every day) exhibits a potent antitumor efficacy in human MDA-MB-231 breast cancer xenograft mouse model[1]. Animal Model: Human MDA-MB-231 breast cancer xenograft mouse model[1] Dosage: 25 mg/kg or 50mg/kg Administration: 25 mg/kg or 50mg/kg; i.p.; every day. Result: Exhibited a potent antitumor efficacy.

[1]. Kunal Nepali, et al. Purine/purine isoster based scaffolds as new derivatives of benzamide class of HDAC inhibitors. Eur J Med Chem. 2020 Jun 15;196:112291.