DBPR112 是一种口服有效的基于氟嘧啶的EGFR抑制剂，对 EGFRWT和 EGFRL858R/T790M的IC50分别为 15 nM 和 48 nM。DBPR112 可以占据 ATP 结合位点。DBPR112 具有显着的抗肿瘤功效。
| 生物活性 | DBPR112 is an orally active furanopyrimidine-basedEGFRinhibitor withIC50s of 15 nM and 48 nM forEGFRWTandEGFRL858R/T790M, respectively. DBPR112 can occupy the ATP-binding site. DBPR112 has significant antitumor efficacy[1]. |
| IC50& Target | EGFRL858R/T790M 48 nM (IC50) | EGFRWT 15 nM (IC50) |
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体外研究
(In Vitro) | DBPR112 (compound 78; 0.32-1000 nM; 16 hours) induces reduction of phosphorylated EGFR in a dose-dependent manner[1].
DBPR112 shows the inhibitory activity against HCC827 (CC50=25 nM), H1975 (CC50=620 nM) and A431 Cell (CC50=1.02 μM) cell lines[1].
DBPR112 occupies the ATP-binding site and interacts with surrounding residues by covalent bonding, hydrogen bonds, and hydrophobic interactions, which give it a potent inhibitory activity against WT EGFR[1].
Western Blot Analysis[1] | Cell Line: | H1975 cells | | Concentration: | 0.32, 1.6, 8.0, 40, 200, 1000 nM | | Incubation Time: | 16 hours | | Result: | Induced reduction of phosphorylated EGFR in a dose-dependent manner in H1975 cells. |
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体内研究
(In Vivo) | DBPR112 (orally; 20-50 mg/kg; 5 days/week for 2 consecutive weeks) significantly reduces tumor growth in HCC827 tumor model. DBPR112 (orally; 50 mg/kg; once a day for 15 days) has a significant antitumor effect (mean tumor growth inhibition of 34%) in H1975 tumor model[1].
DBPR112 (IV; 5 mg/kg) has a T1/2of 2.3 hours, a CL of 55.6 mL/minokg, and a Vssof 8.6 L/kg for rats[1].
| Animal Model: | HCC827 tumor model (6- to 8-week-old athymic NU-Fox1nu nude mice)[1] | | Dosage: | 20, 50 mg/kg | | Administration: | Orally; 5 days/week for 2 consecutive weeks (days 1-5 and 8-12) | | Result: | Significantly reduced tumor growth. |
| Animal Model: | Rats[1] | | Dosage: | 5 mg/kg for IV and 20 mg/kg for PO (Pharmacokinetic Analysis) | | Administration: | IV or PO | | Result: | Had a T1/2of 2.3 hours, a CL of 55.6 mL/minokg, and a Vssof 8.6 L/kg by IV.
Had a T1/2of 3.4 hours, a Cmaxof 508 ng/mL and an AUC of 2978 ng/mLoh by PO. |
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| Clinical Trial | |
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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 : 250 mg/mL(468.50 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.8740 mL | 9.3700 mL | 18.7399 mL | | 5 mM | 0.3748 mL | 1.8740 mL | 3.7480 mL | | 10 mM | 0.1874 mL | 0.9370 mL | 1.8740 mL |
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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: ≥ 2.08 mg/mL (3.90 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.90 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.08 mg/mL (3.90 mM); Suspended solution; Need ultrasonic
此方案可获得 2.08 mg/mL (3.90 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 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： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (3.90 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.90 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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