HDAC6-IN-1 is a potent and selective inhibitor for HDAC6 with an IC50 of 17 nM and shows 25-fold and 200-fold selectivity relative to HDAC1 (IC50=422 nM) and HDAC8 (IC50=3398 nM), respectively
SKLB-23bb is a potent and selective HDAC6 inhibitor, showcasing an IC50 of merely 17 nM. It distinguishes itself by being 25 times more selective against HDAC1 (IC50 = 422 nM) and 200 times more selective against HDAC8 (IC50 = 3398 nM)[1].
体内研究
In vivo studies further underscore SKLB-23bb's efficacy in tumor suppression, both in hematological tumor MV4-11 xenografts and solid tumor HCT116 xenografts, via intravenous administration at a dosage of 50 mg/kg. This treatment resulted in the suppression of MV4-11 and HCT116 cancer cell xenograft growth by 55.0% and 76.3% (TGI values), respectively. Remarkably, the oral administration of SKLB-23bb at 25 mg/kg in the HCT116 xenograft model achieved a TGI value of 60.4%, outperforming the SAHA group treated at 100 mg/kg (59.2% TGI value). The treatment was well-tolerated, with acceptable body weight reduction and no observed adverse effects. SKLB-23bb is characterized by low clearance rates (CL = 7.008 L/kg per hour for iv, CL = 12.877 L/kg per hour for po) and prolonged terminal half-lives (t1/2 = 7.658 hours for iv, t1/2 = 9.62 hours for po), showcasing an excellent oral bioavailability of up to 47.0% in rats[1].
体外研究
TSKLB-23bb exhibits strong antiproliferative effects across a variety of cancer cell lines, demonstrating particularly potent activities against human malignant melanoma A375 cells and cervical cancer HeLa cells with IC50 values of 50 and 49 nM, respectively. The comprehensive evaluation of SKLB-23bb's antiproliferative effectiveness spans 11 types of hematological tumors—including myeloma U266, RPMI8226, human leukemia MV4-11, K562, and human B cell lymphoma Ramos cells—as well as solid tumors like ovarian cancer A2780s, SKOV-3, breast cancer SKBR3, liver cancer HepG2, lung cancer H460, A549, cervical cancer HeLa, and colon cancer HCT116, HT29 cell lines, using MTT assay. Compared to SAHA and ACY-1215 as positive controls, SKLB-23bb significantly inhibits tumor cell proliferation, with IC50 values ranging from 14 to 104 nM in these cell lines[1].
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