KA2507 is a potent, orally active and selective HDAC6 inhibitor, with an IC50 of 2.5 nM. KA2507 shows antitumor activities and immune modulatory effects in preclinical models[1].
IC50 & Target[1]
HDAC6
2.5 nM (IC50)
HDAC8
621 (IC50)
体外研究 (In Vitro)
KA2507 did not inhibit the in vitro proliferation of mouse or human cancer cells at concentrations that are selective for HDAC6 inhibition[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
KA2507 (100-200 mg/kg; p.o.; daily; for 20 days) inhibits tumor growth in the syngeneic B16-F10 mouse melanoma model[1]. KA2507 also demonstrates antitumor efficacy in CT26 and MC38 colorectal cancer models[1]. Analysis of tumor samples also indicates modulation of biomarkers of antitumor immunity at efficacious dosing, with KA2507 administration resulting in reduced STAT3 activation (as measured by phospho-STAT3, an important suppressor of the antitumor immune response), reduced PD-L1 expression, and increased expression of MHC class I[1]. KA2507 exhibits poor oral bioavailability (mice 15%) and Cmax (mice 300 ng/mL) following oral administration (mice 200 mg/kg)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Male C57BL/6 mice, B16-F10 melanoma model[1]
Dosage:
100 mg/kg, 200 mg/kg, 200 mg/kg
Administration:
Oral gavage, daily, for 20 days
Result:
Demonstrated antitumor efficacy.
Animal Model:
Male C57BL/6 mice[1]
Dosage:
200 mg/kg (Pharmacokinetic Analysis)
Administration:
Oral administration
Result:
Oral bioavailability (15%), Cmax (300 ng/mL).
Clinical Trial
分子量
322.32
Formula
C16H14N6O2
CAS 号
1636894-46-6
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Apostolia M Tsimberidou, et al. Preclinical Development and First-in-Human Study of KA2507, a Selective and Potent Inhibitor of Histone Deacetylase 6, for Patients with Refractory Solid Tumors. Clin Cancer Res. 2021 May 4.
KA2507 hydrochloride is a potent and highly selective inhibitor of HDAC6 (IC50=2.5 nM) with no significant toxicities. KA2507 hydrochloride shows antitumor efficacy and immune modulatory effects[1].
体外研究 (In Vitro)
KA2507 hydrochloride does not inhibit the in vitro proliferation of mouse or human cancer cells at concentrations that are selective for HDAC6 inhibition. The anti-proliferative effects are only observed at high concentrations of KA2507 hydrochloride, which combines with the increased acetylation of histone H3 suggests that the anti-proliferative effects of KA2507 hydrochloride are attributable to off-target inhibition of class I HDAC as well as HDAC6[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
KA2507 hydrochloride (100-200 mg/kg; p.o.; daily; for 20 days) inhibits tumor growth in the syngeneic B16-F10 mouse melanoma model[1]. KA2507 hydrochloride also demonstrates antitumor efficacy in CT26 and MC38 colorectal cancer models[1]. Analysis of tumor samples also indicates modulation of biomarkers of antitumor immunity at efficacious dosing, with KA2507 hydrochloride administration resulting in reduced STAT3 activation (as measured by phospho-STAT3, an important suppressor of the antitumor immune response), reduced PD-L1 expression, and increased expression of MHC class I[1]. KA2507 hydrochloride exhibits poor oral bioavailability (mice 15%) and Cmax (mice 300 ng/mL) following oral administration (mice 200 mg/kg)[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Male C57BL/6 mice, B16-F10 melanoma model[1]
Dosage:
100 mg/kg, 200 mg/kg,
Administration:
P.o.; once a day for 20 days
Result:
Inhibited tumor growth in the syngeneic B16-F10 mouse melanoma model.
Animal Model:
Male C57BL/6 mice, B16-F10 melanoma model[1]
Dosage:
200 mg/kg (Pharmacokinetic Analysis)
Administration:
Oral administration
Result:
Oral bioavailability (15%), Cmax (300 ng/mL).
Clinical Trial
分子量
358.78
Formula
C16H15ClN6O2
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
4°C, sealed storage, away from moisture and light
*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
参考文献
[1]. Tsimberidou AM, et al. Preclinical Development and First-in-Human Study of KA2507, a Selective and Potent Inhibitor of Histone Deacetylase 6, for Patients with Refractory Solid Tumors. Clin Cancer Res. 2021;27(13):3584-3594.
