ACY-738 is a potent, selective and orally-bioavailable HDAC6 inhibitor, with an IC₅₀ of 1.7 nM; ACY-738 also inhibits HDAC1, HDAC2, and HDAC3, with IC₅₀s of 94, 128, and 218 nM.

ACY-738 (2.5 μM) increases the acetylated (lysine 40) fraction of α-tubulin in RN46A-B14 cells^[1]. ACY-738 (10 μM) induces cell death comparable to LBH589 and FK228^[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.

ACY-738 (5 mg/kg) leads to significant increase in α-tubulin acetylation in whole-brain lysates. ACY-738 (50 mg/kg) fails to produce an enhancement of locomotor activity in WT mice tested in a home cage environment^[1]. ACY-738 (5 mg/kg) reaches a maximum plasma concentration of 1310 ng/mL at 0.0830 h following treatment. ACY-738 (5 mg/kg BW) alters BM B cell differentiation, but shows no significant effect on IgG and C3 deposition in NZB/W mice. ACY-738 (20 mg/kg) significantly attenuates the severity of proteinuria in NZB/W F1 mice. ACY-738 (5 mg/kg) shows a significant decrease in anti-dsDNA production in NZB/W mice as they aged. ACY-738 (5, 20 mg/kg) attenuates sera IL-1β production as the NZB/W mice aged. ACY-738 (5 mg/kg) significantly reduces glomerular IL-6 and IL-10 mRNA levels by more than 50% while treatment with 20 mg/kg ACY-738 reduced IL-6 and IL-10 mRNA to non-detectable levels^[2].

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.

270.29

C₁₄H₁₄N₄O₂

1375465-91-0

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : ≥ 32 mg/mL (118.39 mM)

* “≥” means soluble, but saturation unknown.

*

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。

In Vivo:

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    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.08 mg/mL (7.70 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (7.70 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

• 2.

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

  Solubility: ≥ 2.08 mg/mL (7.70 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (7.70 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 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
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.08 mg/mL (7.70 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (7.70 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]. Jochems J, et al. Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability. Neuropsychopharmacology. 2014 Jan;39(2):389-400.

  [2]. Regna NL, et al. Specific HDAC6 inhibition by ACY-738 reduces SLE pathogenesis in NZB/W mice. Clin Immunol. 2016 Jan;162:58-73.

  [3]. Mithraprabhu S, et al. Histone deacetylase (HDAC) inhibitors as single agents induce multiple myeloma cell death principally through the inhibition of class I HDAC. Br J Haematol. 2013 Aug;162(4):559-62.

Mice are injected i.p. 5 days/week with the vehicle control (DMSO), ACY-738 treatment at 5 mg/kg (low-dose), or ACY-738 treatment at 20 mg/kg (high-dose) beginning at 22-weeks-of-age until euthanasia at 38 weeks-of-age. The total volume injected is 80 μL. Proteinuria and weight are measured every 2 weeks and blood is collected every four weeks for sera analysis. Proteinuria is measured by a standard semi-quantitative test using Siemens Uristix dipsticks. Results are quantified and scored as follows: dipstick reading of 0 mg/dL = 0, trace = 1, 30-100 mg/dL = 2, 100-300 mg/dL = 3, 300-2000 mg/dL = 4, and 2000 + mg/dL = 5^[2].

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]. Jochems J, et al. Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability. Neuropsychopharmacology. 2014 Jan;39(2):389-400.

  [2]. Regna NL, et al. Specific HDAC6 inhibition by ACY-738 reduces SLE pathogenesis in NZB/W mice. Clin Immunol. 2016 Jan;162:58-73.

  [3]. Mithraprabhu S, et al. Histone deacetylase (HDAC) inhibitors as single agents induce multiple myeloma cell death principally through the inhibition of class I HDAC. Br J Haematol. 2013 Aug;162(4):559-62.