RBN-2397 是一种强效的,跨物种的,且具有口服活性的 NAD+竞争性PARP7抑制剂,IC50值小于 3 nM。RBN-2397 有选择性地结合 PARP7 (Kd=0.001 μM) 并可以恢复干扰素 I 型信号转导。RBN-2397 有潜力用于研究晚期或转移性实体肿瘤。
生物活性 | RBN-2397 is a potent, accross species and orally active NAD+competitive inhibitor ofPARP7(IC50<3 nm). rbn-2397 selectively binds toPARP7(Kd=0.001 μM) and restores IFN signaling. RBN-2397 has the potential for the study of advanced or metastatic solid tumors[1][2]. |
IC50& Target[2] | PARP-7 3 nM (IC50) | PARP-7 1 nM (Kd) |
|
体外研究 (In Vitro) | RBN-2397 (0.0001-100 μM; 24 hours) inhibits cells proliferation with an IC50value of 20 nM in NCI-H1373 lung cancer cells[2].RBN-2397 (0.4 nM-1 μM; 24 hours) shows a restoration of type I IFN response by an increase in STAT1 phosphorylation as a dose-dependent manner in NCI-H1373 human lung cancer cells[2].RBN-2397 (0.0001-1 μM; 24 hours) inhibits cell MARylation in a cell biochemial assay with an EC50value of 1 nM[2].
Cell Proliferation Assay[2] Cell Line: | NCI-H1373 lung cancer cells | Concentration: | 0.0001 μM; 0.001 μM; 0.001 μM; 0.1 μM; 1 μM; 10 μM; 100 μM | Incubation Time: | 24 hours | Result: | Blocked cell proliferation. |
Western Blot Analysis[2] Cell Line: | NCI-H1373 lung cancer cells | Concentration: | 0.4 nM-1 μM | Incubation Time: | 24 hours | Result: | Increased p-STAT1 protein expression. |
|
体内研究 (In Vivo) | RBN-2397 (oral administration; 3-100 mg/kg; once daily; 24-32 days) induces tumor-specific adaptive immune memory in CT26 syngeneic model with durable complete responses in CT26 tumor-bearing BALB/c mice[2].RBN-2397 (oral administration; 3-100 mg/kg; once daily; 32 days) causes complete regressions at the dose 100 mg/kg and exerts a dose-dependent effects on tumor growth at dose levels of ≥30 mg/kg[2].The half-life (t1/2) of RBN-2397 in vivo is 325 mins[2].
Animal Model: | CB17 SCID mice with NCI-H1373 xenografts[2] | Dosage: | 3 mg/kg, 10mg/kg, 30 mg/kg, 100 mg/kg | Administration: | Oral administration; once daily; 24-32 days | Result: | Decreased tumor volume and exerted anti-tumor effects. |
|
Clinical Trial | |
分子量 | |
性状 | |
Formula | |
CAS 号 | |
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 |
|
溶解性数据 | In Vitro: DMSO : 200 mg/mL(382.10 mM;Need ultrasonic) 配制储备液 1 mM | 1.9105 mL | 9.5524 mL | 19.1048 mL | 5 mM | 0.3821 mL | 1.9105 mL | 3.8210 mL | 10 mM | 0.1910 mL | 0.9552 mL | 1.9105 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: 5% DMSO 95% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (4.78 mM); Clear solution 2. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (3.97 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.97 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。 3. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (3.97 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.97 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 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 4. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (3.97 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.97 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。 5. 请依序添加每种溶剂: 1% DMSO 99% saline Solubility: ≥ 0.5 mg/mL (0.96 mM); Clear solution *以上所有助溶剂都可在本网站选购。
|