Fimepinostat (CUDC-907) potently inhibits class IPI3Ks as well as classes I and IIHDACenzymes with anIC₅₀of 19/54/39 nM and 1.7/5.0/1.8/2.8 nM for PI3Kα/PI3Kβ/PI3Kδ and HDAC1/HDAC2/HDAC3/HDAC10 , respectively.

Fimepinostat is a potent pan-inhibitor of HDAC classes I and II enzymes and observed that its potency against class I HDACs is similar to that of LBH589 and greater than that of SAHA. Fimepinostat is also a potent inhibitor of class I PI3K kinases with an IC₅₀of 19, 54, and 39 nM for PI3Kα, PI3Kβ, and PI3Kδ, respectively. Fimepinostat markedly induces p21 protein in H460, a non-small cell lung cancer (NSCLC) cell line. Fimepinostat causes the reduction of both p-STAT3 (Y-705) and p-SRC in RPMI-8226 multiple myeloma cells and reduces both phosphorylated and total protein levels of MET and EGFR as well as HER2 and HER3 in H1975 NSCLC cells and BT-474 breast cancer cells, respectively. Fimepinostat induces caspase-3 and -7 activation in HCT-116 colon cancer cells in a dose-dependent manner. Fimepinostat potently inhibits the growth of cancer cells derived from both hematologic and solid tumors. Fimepinostat potently inhibits the proliferation of cells expressing either mutant or wild-type PI3K^[1].

Oral administration of Fimepinostat inhibits growth of the Daudi cancer cell xenografts in a dose-dependent manner. Tumor stasis is observed at 100 mg/kg in this model without obvious toxicity. Importantly, in the same model, Fimepinostat achieves better efficacy than GDC-0941, SAHA, or a combination of these 2 compounds given at their maximal tolerated doses (MTD). Furthermore, Fimepinostat causes tumor regression or stasis after intravenous (50 mg/kg) or oral administration (100 mg/kg) in a xenograft tumor model of SU-DHL4 diffuse large B-cell lymphoma (DLBCL) and causes tumor stasis in KRAS-mutant A549 NSCLC cell xenografts^[1].

508.55

Solid

C₂₃H₂₄N₈O₄S

1339928-25-4

Room temperature in continental US; may vary elsewhere.

DMSO : 50 mg/mL(98.32 mM;Need ultrasonic)

DMF : 5 mg/mL(9.83 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： 30 %SBE-β-CD

  Solubility: 10 mg/mL (19.66 mM); Suspended solution; Need ultrasonic
• 2.

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

  Solubility: ≥ 2.08 mg/mL (4.09 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.09 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% (20%SBE-β-CDin saline)

  Solubility: ≥ 2.08 mg/mL (4.09 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.09 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 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
• 4.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: 2.08 mg/mL (4.09 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.08 mg/mL (4.09 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。