RMC-6272 (RM-006) is a bi-steric mTORC1-selective inhibitor. RMC-6272 exhibits potent and selective (> 10-fold) inhibition of mTORC1 over mTORC2. RMC-6272 shows improved inhibition of mTORC1 in comparison to Rapamycin, and induces more cell death in TSC2 null tumors^[1].

RMC-6272 shows more effective growth inhibition in multiple TSC1 or TSC2 mutant tumor cell lines compared to Rapamycin. RMC-6272 causes a more profound growth inhibition in the TSC1 or TSC2 mutant cells than the wild type cells. RMC-6272 at ~1 nM shows near complete inhibition of p4E-BP1^T37/46, while inhibition of pS6^S240/244 levels is similar for Rapamycin and RM compounds^[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.

RMC-6272 markedly reduces kidney tumor burden in Tsc2^+/- A/J mice after four weeks of treatment. Tumor regrowth is assessed two months after treatment cessation, tumor burden is significantly reduced in the RMC-6272 group as compared to the Rapamycin and MLN0128 groups^[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.

1850.22

C₉₅H₁₄₁FN₆O₂₇S

2382769-46-0

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Heng Du, et al. Bi-steric mTORC1-selective inhibitors demonstrate improved potency and efficacy in tumors with mTORC1 hyperactivation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1026.

RMC-0331 (RM-023) is a potent, selective and orally bioavailable SOS1 inhibitor. RMC-0331 is an in vivo tool compound that blocks RAS activation via disruption of the RAS-SOS1 interaction^[1].

RMC-0331 has an IC₅₀ of 71 nM measuring by the rate of GDP/GTP exchange in vitro^[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.

RMC-0331 (100-250 mg/kg; p.o.; qd; immunocompetent mice) shows single agent anti-tumor activity in SHP2-mutant models^[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.

499.91

C₂₂H₂₅ClF₃N₅O₃

2488788-52-7

Room temperature in continental US; may vary elsewhere.

DMSO : 125 mg/mL (250.05 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 (4.16 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.16 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 (4.16 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.08 mg/mL (4.16 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 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 (4.16 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.16 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]. Andreas Buckl, et al. Discovery of a Potent, Selective and Orally Bioavailable SOS1 Inhibitor, RMC-0331 (RM-023), an in vivo Tool Compound that Blocks RAS Activation via Disruption of the RAS-SOS1 Interaction.