RVX-297 是一种高效、具有口服活性、对BD2有选择性的BET抑制剂。RVX-297 对 BRD2(BD2)，BRD3(BD2)，BRD4(BD2) 的IC50分别为 0.08、0.05、0.02 μM。RVX-297 抑制多种免疫细胞炎症基因的表达。RVX-297 对临床前模型急性炎症和自身免疫的有效。
| 生物活性 | RVX-297 is a potent, orally activeBET bromodomaininhibitor with selectivity forBD2. RVX-297 showsIC50s of 0.08, 0.05, and 0.02 μM for BRD2(BD2), BRD3(BD2), and BRD4(BD2), respectively. RVX-297 suppresses inflammatory gene expression in multiple immune cell types. RVX-297 is effective in acute inflammation and autoimmunity models[1][2]. |
| IC50& Target[2] | BRD2 (BD1) 3.76 μM (IC50) | BRD2 (BD2) 0.08 μM (IC50) | BRD3 (BD1) 2.34 μM (IC50) | BRD3 (BD2) 0.05 μM (IC50) | BRD4 (BD1) 1.16 μM (IC50) | BRD4 (BD2) 0.02 μM (IC50) | BRDT (BD1) 2.69 μM (IC50) |
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体外研究
(In Vitro) | RVX-297 (1-30 μM; 24 hours) decreases proinflammatory gene expression in synovial fibroblasts[1].
RVX-297 displaces BET proteins from the promoters of sensitive genes and disrupted recruitment of active RNA polymerase II, a property shared with pan-BET inhibitors that nonselectively bind BET BDs[1].
RVX-297 reduces gene expression of inflammatory mediators in vitro. RVX-297 suppresses IL-6 gene induction in human U937 macrophages, mouse primary B cells isolated from the spleen, mouse BMDMs, and THP-1 monocytes in a dose-dependent manner. RVX-297 represses IL-1β expression in LPS-stimulated mouse BMDMs, with an IC50of 0.4-3 μM. RVX-297 inhibits MCP-1 expression in unstimulated human PBMCs with an IC50of 0.4 μM. RVX-297 inhibits antigen stimulation of T cells and the induction of IL-17 expression[1].
RT-PCR[1] | Cell Line: | Synovial fibroblasts | | Concentration: | 1-30 μM | | Incubation Time: | 24 hours | | Result: | Downregulated IL-6 and VCAM-1 gene expression in synovial fibroblasts. |
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体内研究
(In Vivo) | RVX-297 (25-75 mg/kg; p.o.; per day for 6 day) inhibits progression of pathology in the rat collagen-induced arthritis model[1].
RVX-297 (75-150 mg/kg) inhibits progression of pathology in the mouse collagen-induced arthritis model[1].
RVX-297 suppresses cytokine production in LPS-treated mice[1].
| Animal Model: | Female Lewis rats are 6-8 weeks old, approximately 150 g (rat collagen-induced arthritis)[1] | | Dosage: | 25, 50, and 75 mg/kg | | Administration: | P.o.; per day for 6 days | | Result: | Prevented swelling and inflammation of the ankle and knee joints. |
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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 : 50 mg/mL(118.06 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.3613 mL | 11.8064 mL | 23.6128 mL | | 5 mM | 0.4723 mL | 2.3613 mL | 4.7225 mL | | 10 mM | 0.2361 mL | 1.1806 mL | 2.3613 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: ≥ 2.08 mg/mL (4.91 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.91 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 (4.91 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.91 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。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (4.91 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.91 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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