Pracinostat is a potent histone deacetylase (HDAC) inhibitor, with IC₅₀s of 40-140 nM, used for cancer research.

Pracinostat (SB939) is a potent novel hydroxamate-based inhibitor of HDACs class I, II, and IV, inhibiting the isolated enzymes with a K_i of 19 to 48 nM (class I), 16 to 247 nM (class II), and 43 nM (class IV), but with no activity against the class III isoenzyme SIRT I. SB939 has effects on HCT-116 colon cancer cell line and the HL-60 acute myeloid leukemia cell line, with IC₅₀s of 0.48 μM and 70 nM, respectively. SB939 does not inhibit the proliferation of normal human dermal fibroblasts at concentrations up to 100 μM^[1]. Pracinostat (SB939, compound 3) inhibits CYP2C19 with IC₅₀ of 5.78 μM. SB939 shows potent activities against A2780, COLO 205, HCT-116, and PC-3 cell lines, with IC₅₀s of 0.48 ± 0.21, 0.56 ± 0.08, 0.48 ± 0.27, and 0.34 ± 0.06^[2]. Pracinostat downregulates JAK and FLT3 signaling in JAK2^V617F and FLT-ITD cell lines, and shows synergy in combination with pacritinib. Pracinostat and pacritinib show in vitro synergy on STAT signaling and apoptosis. Pracinostat potently inhibits proliferation of different AML subtypes as a single agent and is synergistic with pacritinib in JAK2^V617F or FLT3-ITD AML cell lines^[3].

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.

Pracinostat (SB939, 25-100 mg/kg) shows significant dose-dependent growth inhibition of HCT-116 xenografts. SB939 selectively accumulates in tumor tissue. SB939 (50 or 75 mg/kg) exhibits anti-tumor activities in the Apcmin genetic colon cancer mouse model^[1]. Pracinostat (25 or 50 mg/kg per day for 21 days) induces significant inhibition of tumor growth (TGI), by 59 and 116%, respectively, in mice bearing MV4-11 xenografts. Pracinostat (75 mg/kg, q.o.d) in combination with pacritinib is efficacious and synergistic in vivo in two different models of human AML. Pracinostat and pacritinib have synergistic effects on AML-induced plasma cytokines/growth factors/chemokines^[3].

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.

358.48

C₂₀H₃₀N₄O₂

929016-96-6

Room temperature in continental US; may vary elsewhere.

DMSO : 250 mg/mL (697.39 mM; Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.75 mg/mL (7.67 mM); Clear solution

  此方案可获得 ≥ 2.75 mg/mL (7.67 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 27.5 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 2.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.08 mg/mL (5.80 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.80 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.08 mg/mL (5.80 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.80 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Novotny-Diermayr V, et al. SB939, a novel potent and orally active histone deacetylase inhibitor with high tumor exposure and efficacy in mouse models of colorectal cancer. Mol Cancer Ther. 2010 Mar;9(3):642-52.

  [2]. Wang H, et al. Discovery of (2E)-3-{2-butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl}-N-hydroxyacrylamide (SB939), an orally active histone deacetylase inhibitor with a superior preclinical profile. J Med Chem. 2011 Jul 14;54(13):4694-720.

  [3]. Novotny-Diermayr V, et al. The oral HDAC inhibitor pracinostat (SB939) is efficacious and synergistic with the JAK2 inhibitor pacritinib (SB1518) in preclinical models of AML. Blood Cancer J. 2012 May;2(5):e69.

Cells are seeded in 96-well plates at a predetermined optimal density, in the log growth phase, and rested for 24 h (adherent cells) or 2 h (suspension cells), respectively, before treatment with SB939. All experiments are done in triplicates for 96 h, with 1% solvent, using either the CyQUANT Cell proliferation assay kit for adherent cells or the CellTiter96 Aqueous One solution cell proliferation kit for suspension cells, in a total volume of 100 μL with SB939 concentrations from 100 μM to 1.5 nM in nine serial dilution steps. IC₅₀ are determined using the XLfit software^[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.

Male Apc^Min/+ mice and female C57BL/6 mice are fed a standard rodent diet. Mice with the confirmed mutation, between 16 and 20.5 wk of age, with a positive scoring in the hemocult assay are recruited to the experiment. During treatment, mice are injected i.p. with 40 mg/kg of 5-FU in a volume of 200 μL per 20 g body weight, once daily, for 5 d of treatment, followed by a 9-d recovery period and an additional 5 d of treatment. Treatment with SB939 per oral at 50 or 75 mg/kg once daily is given continuously for 21 d. At the last day of the treatment, the small intestine, caecum, and colon are removed; fixed by multiple injections of 4% PBS-buffered formaldehyde into the gut lumen; cut into segments; and spread flat on a plastic film in a formaldehyde bath. Tumor load is measured in a dissection microscope. Assessment and analysis of the samples are done blinded^[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.

• [1]. Novotny-Diermayr V, et al. SB939, a novel potent and orally active histone deacetylase inhibitor with high tumor exposure and efficacy in mouse models of colorectal cancer. Mol Cancer Ther. 2010 Mar;9(3):642-52.

  [2]. Wang H, et al. Discovery of (2E)-3-{2-butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl}-N-hydroxyacrylamide (SB939), an orally active histone deacetylase inhibitor with a superior preclinical profile. J Med Chem. 2011 Jul 14;54(13):4694-720.

  [3]. Novotny-Diermayr V, et al. The oral HDAC inhibitor pracinostat (SB939) is efficacious and synergistic with the JAK2 inhibitor pacritinib (SB1518) in preclinical models of AML. Blood Cancer J. 2012 May;2(5):e69.