M3258 is an orally bioavailable, potent, reversible and highly selective immunoproteasome subunit LMP7 (β5i) inhibitor. M3258 exerts high biochemical (IC₅₀=3.6 nM) and cellular (IC₅₀=3.4 nM) potency against the LMP7 subunit. M3258 shows strong antitumor efficacy in multiple myeloma xenograft models. M3258 leads to a significant and prolonged suppression of tumor LMP7 activity and ubiquitinated protein turnover and the induction of apoptosis in multiple myeloma cells^[1][2].

LMP7^[1]

M3258 inhibits human LMP7 with a mean IC₅₀ of 4.1 nM. M3258 displays weak activity against the constitutive proteasome subunit β5 (mean IC₅₀=2519 nM). M3258 potently inhibits LMP7 in the human multiple myeloma cell lines MM.1S and U266B1 and in human, rat, and dog PBMCs with IC₅₀s between 2 and 37 nM^[2].
M3258 induces a >four fold accumulation of ubiquitinated proteins with an EC₅₀ of 1980 nM in MM.1S cells. M3258 interferes with immunoproteasome function. M3258 also induces apoptosis assessed by caspase 3/7 activity (EC₅₀=420 nM;>3.5-fold induction) and reduces MM.1S cell viability (IC₅₀=367 nM)^[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.

M3258 (1 mg/kg; 10 mg/kg) shows superior antitumor efficacy in selected multiple myeloma and mantle cell lymphoma xenograft models compared with the approved nonselective proteasome inhibitors bortezomib and ixazomib^[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.

329.16

C₁₇H₂₀BNO₅

2285330-15-4

Room temperature in continental US; may vary elsewhere.

DMSO : 250 mg/mL (759.51 mM; Need ultrasonic)

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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
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• 1.

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

  Solubility: ≥ 2.08 mg/mL (6.32 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (6.32 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 (6.32 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (6.32 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 (6.32 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (6.32 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]. Klein M, et al. Structure-Based Optimization and Discovery of M3258, a Specific Inhibitor of the Immunoproteasome Subunit LMP7 (β5i) [published online ahead of print, 2021 Jul 6]. J Med Chem. 2021;10.1021/acs.jmedchem.1c00604.

  [2]. Sanderson MP, et al. M3258 Is a Selective Inhibitor of the Immunoproteasome Subunit LMP7 (β5i) Delivering Efficacy in Multiple Myeloma Models [published online ahead of print, 2021 May 27]. Mol Cancer Ther. 2021;10.1158/1535-7163.MCT-21-0005.