M3258|cas:2285330-15-4|西域试剂

M3258,98.0%

产品编号：Bellancom-111790| CAS NO：2285330-15-4| 分子式：C₁₇H₂₀BNO₅| 分子量：329.16

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货号	包装	价格	库存与货期	购买量	操作
Bellancom-111790		￥4900.00	杭州北京（现货）
Bellancom-111790		￥7900.00	杭州北京（现货）

增值税发票√顺丰快递√订货电话：18601927057

M3258

产品介绍

M3258 是一种口服生物利用度高、有效、可逆、高选择性的免疫蛋白酶体亚单位 LMP7 (β5i) 抑制剂。M3258 对 LMP7 的 IC₅₀ 为 3.6 nM，在细胞中 IC₅₀ 为 3.4 nM。M3258 在多发性骨髓瘤异种移植模型中显示出很强的抗肿瘤作用。在多发性骨髓瘤细胞中，M3258 导致肿瘤 LMP7 活性和泛素化蛋白转换的显著且持久的抑制以及诱导凋亡 (apoptosis)。

生物活性

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.

体外研究

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.
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).

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay

Cell Line:	MM.1S cells
Concentration:	0.01-100 nM
Incubation Time:	2 hours
Result:	Potently inhibited LMP7 in the human multiple myeloma cell lines MM.1S (IC₅₀=2.2 nM).

体内研究
(In Vivo)

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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Female H2d Rag2 mice or female CB-17 SCID mice (U266B1 subcutaneous xenograft model; MM.1S subcutaneous xenograft model)
Dosage:	1 mg/kg in U266B1 subcutaneous xenograft model; 10 mg/kg in MM.1S subcutaneous xenograft model
Administration:	P.o.; either once daily, every 2 days or twice weekly (days 1 and 4)
Result:	Displayed significant and strong antitumor efficacy.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Female H2d Rag2 mice or female CB-17 SCID mice (U266B1 subcutaneous xenograft model; MM.1S subcutaneous xenograft model)
Dosage:	1 mg/kg in U266B1 subcutaneous xenograft model; 10 mg/kg in MM.1S subcutaneous xenograft model
Administration:	P.o.; either once daily, every 2 days or twice weekly (days 1 and 4)
Result:	Displayed significant and strong antitumor efficacy.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Female H2d Rag2 mice or female CB-17 SCID mice (U266B1 subcutaneous xenograft model; MM.1S subcutaneous xenograft model)
Dosage:	1 mg/kg in U266B1 subcutaneous xenograft model; 10 mg/kg in MM.1S subcutaneous xenograft model
Administration:	P.o.; either once daily, every 2 days or twice weekly (days 1 and 4)
Result:	Displayed significant and strong antitumor efficacy.

性状

Solid

溶解性数据

In Vitro:

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

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	3.0380 mL	15.1902 mL	30.3804 mL
5 mM	0.6076 mL	3.0380 mL	6.0761 mL
10 mM	0.3038 mL	1.5190 mL	3.0380 mL

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 (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。