AG-270 是非竞争性的、首创的、可逆的、具有口服活性的MAT2A变构抑制剂,其IC50值为 14 nM。
生物活性 | AG-270 is an allosteric, noncompetitive, first-in-class, reversible and orally activeMAT2Ainhibitor, with anIC50of 14 nM[1].
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体外研究 (In Vitro) | AG-270 demonstrates potent reduction in levels of intracellularSAM, as well as MTAP-null–selective antiproliferative activity in the HCT116 MTAP isogenic cell modelin vitro[1]. AG-270 exhibits an IC50of 20 nM in HCT116 MTAP-null cell SAM at 72 h[1]. MAT2A is a key enzyme in the methionine salvage pathway, responsible for generating the universal methyl donor, S-adenosylmethionine (SAM)[2].
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体内研究 (In Vivo) | AG-270 shows excellent microsomal, hepatocyte, and in vivo metabolic stability across species (human, mouse, rat, dog, and monkey). AG-270 exhibits T1/2 values of 5.9 h, 4.2 h, 4.8 h and 21.3 h in mouse, rat, monkey and dog, respectively[1]. AG-270 (200 mg/kg, orally, q.d. for 38 days) results in dose-dependent reduction in tumor SAM levels and tumor growth of KP4 MTAP-null xenografts and is well tolerated, with mean body weight loss<5%[1]. Combining AG-270 with taxanes and gemcitabine yielded additive-tosynergistic antitumor activity, with the docetaxel combination yielding 50% complete tumor regressions in select models; combination benefits are observed in PDX models derived from esophageal, NSCLC, and pancreatic cancers[2].
Animal Model: | Pancreatic KP4MTAP-null xenograft mouse model[1].
| Dosage: | 10-200 mg/kg. | Administration: | Orally, q.d. for 38 days. | Result: | Led to dose-dependent reductions in tumor SAM levels and tumor growth of KP4 MTAP-null xenografts (TGI = 36% (10 mg/kg), 48% (30 mg/kg), 66% (100 mg/kg), 67% (200 mg/kg). |
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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 : 8.33 mg/mL(17.01 mM;ultrasonic and warming and heat to 60℃) 配制储备液 1 mM | 2.0426 mL | 10.2130 mL | 20.4261 mL | 5 mM | 0.4085 mL | 2.0426 mL | 4.0852 mL | 10 mM | 0.2043 mL | 1.0213 mL | 2.0426 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: ≥ 4.75 mg/mL (9.70 mM); Clear solution
此方案可获得 ≥ 4.75 mg/mL (9.70 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 47.5 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: ≥ 4.75 mg/mL (9.70 mM); Clear solution
此方案可获得 ≥ 4.75 mg/mL (9.70 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 47.5 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。 *以上所有助溶剂都可在本网站选购。
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