SAR-260301 is an orally available and selective PI3Kβ inhibitor with an IC₅₀ of 23 nM^[1][2].

In the UACC-62 tumor cell line assay, SAR-260301 inhibits pAktS473 with a measured IC₅₀ at 0.06 μM and an estimated IC₉₀ at 2 μM^[1]. In MEF-3T3-myr-p110β mechanistic model, SAR260301 inhibits PI3Kβ-dependent proliferation/viability in low serum conditions with an IC₅₀ of 196 nM. In PTEN-deficient human prostate tumor cells, SAR260301 inhibits LNCaP cell proliferation in low and high serum conditions with IC₅₀ values of 2.9 and 5.0 μM, respectively, after 4-day treatment, whereas it is inactive in these conditions in PC3 cells at concentrations up to 10 μM, despite target engagement. After prolonged treatment, SAR260301 at 3 or 10 μM inhibits PC3 cell proliferation in low serum conditions, with a cytostatic effect achieved for 14 days, despite some cell death induction observed at 10 μM. SAR260301 also leads to antitumor activities in PTEN-deficient/BRAF-mutant human melanoma cells, inhibiting cell proliferation with IC₄₀ values of 6.5 and 3.3 μM for UACC-62 and WM-266.4, respectively, after 4-day treatment^[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.

SAR-260301 displays antitumor efficacy in human PTEN-deficient melanoma models in mice as a single agent. SAR-260301 treatment leads to a statistically significant tumor growth inhibition as measured by a ΔT/ΔC of 39% (p = 0.054 versus control mice) on day 15 post-tumor implantation. SAR-260301 is well tolerated at the active dose, with no sign of toxicity and no body weight loss. Oral administration of SAR-260301 reveals sustained target inhibition (≥50%) of pAkt-S473 for at least 7 h. SAR-260301 has moderate terminal elimination half-life (t_1/2=0.87 h, 1.4 h, 2.5 h, 0.87h, 6.9 h and 4.5 h for female SCID mice (3 mg/kg, iv), mice (10 mg/kg, po), mice (100 mg/kg, po), female nude rats (3 mg/kg, iv), rat (10 mg/kg, po), male beagle dogs (10 mg/kg, po))^[1].

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.

354.40

C₁₉H₂₂N₄O₃

1260612-13-2

Room temperature in continental US; may vary elsewhere.

DMSO : 125 mg/mL (352.71 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°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。

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 (5.87 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.87 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 (5.87 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.87 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 (5.87 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.87 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]. Certal V, et al. Discovery and optimization of pyrimidone indoline amide PI3Kβ inhibitors for the treatment of phosphatase and tensin homologue (PTEN)-deficient cancers. J Med Chem. 2014 Feb 13;57(3):903-20.

  [2]. Bonnevaux H, et al. Concomitant Inhibition of PI3Kβ and BRAF or MEK in PTEN-Deficient/BRAF-Mutant Melanoma Treatment: Preclinical Assessment of SAR260301 Oral PI3Kβ-Selective Inhibitor. Mol Cancer Ther. 2016 Jul;15(7):1460-71.

Cell proliferation is measured by quantifying intracellular ATP using CellTiter-Glo kit. Cells seeded into 96-well black microplates in complete medium, are treated with single or combined agents (e.g., SAR260301) 0.3 nM-30 μM (0.1% DMSO final concentration) for 96 hours^[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.

Mice^[1]
SAR-260301 is evaluated for its antitumor effects in UACC-62 melanoma subcutaneous xenografts in SCID mice. Tumors are allowed to reach at least 150 mm³ before treatment, and tumor volume is measured regularly over the treatment period. Mice are treated orally with SAR-260301 at the dose of 150 mg/kg using a bidaily (BID) schedule in order to favor sustained pathway inhibition and allow comparison with the study performed in PC3 model^[1].

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]. Certal V, et al. Discovery and optimization of pyrimidone indoline amide PI3Kβ inhibitors for the treatment of phosphatase and tensin homologue (PTEN)-deficient cancers. J Med Chem. 2014 Feb 13;57(3):903-20.

  [2]. Bonnevaux H, et al. Concomitant Inhibition of PI3Kβ and BRAF or MEK in PTEN-Deficient/BRAF-Mutant Melanoma Treatment: Preclinical Assessment of SAR260301 Oral PI3Kβ-Selective Inhibitor. Mol Cancer Ther. 2016 Jul;15(7):1460-71.