Pan-RAS-IN-1 is a pan-Ras inhibitor that disrupts the interaction of Ras proteins and their effectors.

Pan-RAS-IN-1 binds to KRas^G12D-GppNHp with an affinity less than 20 μM. Pan-RAS-IN-1 binds to Ras proteins and exhibits lethality in cells partially dependent on expression of Ras proteins. The potency of pan-RAS-IN-1 correlates with the degree of dependency on the mutated isoform over a 5-fold concentration range. At some concentrations, pan-RAS-IN-1 is cytostatic, possibly due to pan-RAS inhibition. Pan-RAS-IN-1 is evaluated in primary T cell acute lymphoblastic leukemia (T-ALL) cells. Selective lethality is observed, with mutant NRAS cells retaining only 20%-40% viability after 5 μM treatment^[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.

Pan-RAS-IN-1 administration results in inhibition of tumor growth over 15 days of treatment. Pan-RAS-IN-1-treated mice exhibits decreased tumor pERK levels compared with vehicle treated mice. A modest increase in cleaved caspase-3 is also observed, showing that in this model, pan-RAS-IN-1 has the capacity to induce caspase activation^[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.

717.65

C₃₆H₄₁Cl₂F₃N₆O₂

1835283-94-7

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : ≥ 50 mg/mL (69.67 mM)

* “≥” means soluble, but saturation unknown.

*

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: ≥ 2.5 mg/mL (3.48 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (3.48 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 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: ≥ 2.5 mg/mL (3.48 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (3.48 mM，饱和度未知) 的澄清溶液。

  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 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: ≥ 2.5 mg/mL (3.48 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (3.48 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。

• [1]. Welsch ME, et al. Multivalent Small-Molecule Pan-RAS Inhibitors. Cell. 2017 Feb 23;168(5):878-889.e29.

For 384-well cancer cell viability assays, cells are trypsinized, counted, and seeded into 384-well plates at 1,000 cells/well. After 16 hr, pan-RAS-IN-1 (from 10 mM stocks in DMSO) are arrayed in an 8-point or 16-point dilution series in 384-well polypropylene plates. Compound solutions are transferred at a 1:5 dilution into the assay plates. After 48 hr, a 50% Alamar blue solution is added to a final concentration of 10% Alamar blue. After 6 hr of incubation, fluorescence intensity is determined at 535 and 590 nm^[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.

Mice: Mice tumor Xenograft are dosed with 180 mg/kg pan-RAS-IN-1 orally (12 mg/mL, 10% DMSO, pH 4), vehicle orally, or by a combination of i.p. and i.v. injections at 30 mg/kg (4 mg/mL, 5% DMSO in HBSS at pH 4). Over 14 d, mice receive a total of 10 doses of pan-RAS-IN-1 or vehicle orally, or six i.p. injections and 4 i.v. injections. Tumor size is measured by electronic caliper every 2 d and calculated^[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]. Welsch ME, et al. Multivalent Small-Molecule Pan-RAS Inhibitors. Cell. 2017 Feb 23;168(5):878-889.e29.