双靶向HDAC抑制剂和ATM激活剂SP-1-303抑制雌激素受体阳性乳腺癌细胞生长，本研究中PK实验通过美迪西进行

Dual-targeting chromatin regulation and DNA damage repair signaling presents a promising avenue for cancer therapy.

SP-1-303 acts as a class I isoform selective histone deacetylase (HDAC) inhibitor and an activator of the ataxia-telangiectasia mutated protein (ATM). SP-1-303 emerges as a novel second generation class I (HDAC1 and HDAC3) selective HDAC inhibitor, and ATM activator, capable of modulating estrogen receptor (ER) expression, and inhibiting growth of ER+ breast cancer (BC) cells. Combined targeting of class I HDACs and ATM by SP-1-303 offers a promising therapeutic approach for treating ER+ breast cancers and supports further preclinical evaluation.

Pharmacokinetic (PK) analysis of SP-1-303

SP-1-303 was administered intravenously at 20 mg/kg in Sprague-Dawley rats (n = 3). Selected PK parameters were determined at various time points (0-8hrs) in blood samples. Pharmacokinetic parameters are as follows: Cmax, the maximum plasma concentration; tmax, the time to reach maximum plasma concentration; AUC, the area under the compound concentration versus time curve; t1/2, the elimination half-life. Pharmacokinetic studies performed by Medicilon.

Pharmacokinetic evaluation demonstrates an area under the curve (AUC) of 5227.55 ng/ml × h with an elimination half-life of 1.26 h following intravenous administration in a rat model.

Reference:

Mira Jung, et al. Dual-targeting class I HDAC inhibitor and ATM activator, SP-1-303, preferentially inhibits estrogen receptor positive breast cancer cell growth. PLoS One . 2024 Jul 15;19(7):e0306168. doi: 10.1371/journal.pone.0306168.