P005091 is a selective and potent inhibitor of ubiquitin-specific protease 7(USP7) with anEC₅₀ of 4.2 μM.

EC50: 4.2 μM (USP7)

P005091 is a trisubstituted thiophene with dichlorophenylthio, nitro, and acetyl substituents mediating anti-USP7 activity. P005091 exhibits potent, specific, and selective deubiquitylating activity against USP7. In contrast, P005091 does not inhibit other DUBs or other families of cysteine proteases tested (EC₅₀>100 mM). P005091 inhibits the labeling of USP7 with HA-UbVME in a concentration-dependent manner. USP7-mediated cleavage of high molecular weight polyubiquitin chains is inhibited in a dose-dependent manner by P005091. Moreover, P005091 inhibits USP7- but not USP2- or USP8-mediated cleavage of poly K48-linked ubiquitin chains. USP7 inhibition by P005091 induces HDM2 polyubiquitylation and accelerates degradation of HDM2. P005091 inhibits USP7 deubiquitylating activity, without blocking proteasome activity in MM Cells. P005091 inhibits growth in MM cells and overcomes bortezomib-resistance. P005091 induces a dose-dependent decrease in viability of various MM cell lines, including those that are resistant to conventional therapies dexamethasone (Dex) (MM.1R), doxorubicin (Dox-40), or melphalan (LR5) (IC₅₀range 6-14 μM). P005091 overcomes bone marrow stromal cell-induced growth of MM Cells. P005091 decreases HDM2 and HDMX, as well as upregulated p53 and p21 levels. Overall, P005091-induced cytotoxicity is mediated in part via HDM2-p21 signaling axis and although p53 is upregulated in response to P005091 treatment, the cytotoxic activity of P005091 is not dependent on p53^[1].

In animal tumor model studies, P005091 is well tolerated, inhibits tumor growth, and prolongs survival. Combining P005091 with lenalidomide, HDAC inhibitor SAHA, or dexamethasone triggers synergistic anti-MM activity^[1].

348.22

Solid

C₁₂H₇Cl₂NO₃S₂

882257-11-6

Room temperature in continental US; may vary elsewhere.

1-Methyl-2-pyrrolidinone : 100 mg/mL(287.17 mM;Need ultrasonic)

DMSO : 25 mg/mL(71.79 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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 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： 4% NMP    3%Tween-80   20%PEG400   73% ddH2O

  Solubility: 8 mg/mL (22.97 mM); Suspended solution; Need ultrasonic
• 2.

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

  Solubility: 2.5 mg/mL (7.18 mM); Suspended solution; Need ultrasonic and warming

  此方案可获得 2.5 mg/mL (7.18 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 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: ≥ 2.5 mg/mL (7.18 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (7.18 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。