Batoprotafib (TNO155) 是一种有效的，选择性的，和具有口服活性野生型SHP2的变构抑制剂 (IC50= 0.011 μM)。Batoprotafib 有研究 RTK 依赖性恶性肿瘤的潜力，尤其是晚期实体瘤。
| 生物活性 | Batoprotafib (TNO155) is a potent selective and orally active allosteric inhibitor of wild-typeSHP2(IC50=0.011 μM). Batoprotafib has the potential for the study of RTK-dependent malignancies, especially advanced solid tumors[1]. |
| IC50& Target | |
体外研究
(In Vitro) | Batoprotafib shows an IC50of 0.008 μM in KYSE520 pERK assay and shows an IC50of 0.100 μM in KYSE520 5-day cell proliferation assay. The off-target IC50values are 18 μM, 6.9 μM, and 11 μM for Cav1.2, VMAT, and SST3, respectively[1].Batoprotafib (0-1000 nM; 6 days) inhibits the viability of NCI-H3255, HCC827, and PC9 cells with IC50values lower than 1.5 μM. Batoprotafib is efficacious in EGFR-mutant NSCLC cell lines[2].
Batoprotafib is efficacious in acquired resistance models of EGFR inhibitors and demonstrates combination benefit with EGFR inhibitors[2].
Batoprotafib enhances the efficacy of KRASG12Cinhibitors against KRASG12Clung and colorectal cancers[2].
Batoprotafib inhibits immune-suppressive macrophages and synergizes with PD1 blockade[2].
Cell Proliferation Assay[2] | Cell Line: | PC-9, PC-9 EGFRT790M/C797S, HCC827, HCC827-GR (gefinitib-resistant) | | Concentration: | 0-1000 nM | | Incubation Time: | 6 days | | Result: | Inhibited cell viability with IC50s of 1.56, 1.38, 0.77 and 1.38 μM against PC-9 and PC-9 EGFRT790M/C797S, HCC827 and HCC827-GR cells, respectively. |
Western Blot Analysis[2] | Cell Line: | PC-14 (EGFRex19del) | | Concentration: | 3 μM | | Incubation Time: | 4h and 24 h | | Result: | Effectively reduced p-ERK levels at 4 hours but suffered a rebound at 24 hours. |
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体内研究
(In Vivo) | The oral bioavailability in mouse, rat and money are 78%, 86%, and 60%, respectively[1].
Batoprotafib (20 mg/kg; p.o.; twice daily for 40 days) inhibits tumor growth and is more effective when combined withDabrafenib(HY-14660) plusTrametinib(HY-10999) in nude mice bearing HT-29 xenografts[2].
Batoprotafib (7.5 mg/kg; p.o.; b.i.d. or q.d. for 36 days) plusJDQ-443(HY-139612) (100 mg/kg; p.o.; q.d.) improves the single-agent activity of JDQ443 inKRASG12C-mutated cell-derived (CDX) models in nude mice[3].
| Animal Model: | Female athymic nude mice bearing HT-29 xenografts[2] | | Dosage: | 20 mg/kg alone or 10 mg/kg in combination with Dabrafenib and Trametinib | | Administration: | PO, twice daily for 40 days | | Result: | Resulted in moderate tumor growth inhibition. Maintained tumor stasis for more than 40 days when combined with Dabrafenib plus Trametinib. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(236.99 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.3699 mL | 11.8497 mL | 23.6995 mL | | 5 mM | 0.4740 mL | 2.3699 mL | 4.7399 mL | | 10 mM | 0.2370 mL | 1.1850 mL | 2.3699 mL |
*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。 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 (5.92 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.92 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (5.92 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.92 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 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 5% DMSO 40%PEG300 5%Tween-80 50% saline Solubility: ≥ 2.5 mg/mL (5.92 mM); Clear solution 4. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (4.93 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.93 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。 *以上所有助溶剂都可在本网站选购。
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