TP-472 是一种选择性的BRD9/7抑制剂，对 BRD9 和 BRD7 作用的Kd值分别为 33 nM 和 340 nM。TP-472 对 BRD9 的选择性比 BRD7 以外的其他溴结构域家族成员高 30 倍以上。TP-472 诱导黑色素瘤细胞凋亡 (apoptosis)。
| 生物活性 | TP-472 is a selectiveBRD9/7inhibitor, withKds of 33 nM and 340 nM forBRD9andBRD7, respectively. TP-472 exhibits >30-fold selectivity forBRD9over other bromodomain family members exceptBRD7[1][2]. TP-472 inducesapoptosisof melanoma cells[3]. |
| IC50& Target[1] | BRD9 33 nM (Kd) | BRD7 0.34 μM (Kd) |
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体外研究
(In Vitro) | TP-472 (1 μM, 3 μM; 24-216 hours) yields concentration-dependent growth defects in ESCs[2].
TP-472 (0.1-10 μM; 24 h) effectively inhibits the growth of both the BRAF mutant melanoma cell lines at 5 and 10 μM concentrations[3].
TP-472 (for 2 weeks) also strongly inhibits the long-term survival of multiple melanoma cell lines (M14, SKMEL-28, A375, and A2058) at concentrations of 5 and 10 μM[3].
TP-472 (5-10 μM; 24 h) treatment downregulates genes encoding various extracellular matrix (ECM) proteins, including integrins, collagens, and fibronectins in A375 cells[3].
TP-472 (0.1-10 μM; 24 h) results in the upregulation of pro-apoptotic genes (BAX, MDM2, CDKN1A) in A375 cells[3].
Cell Viability Assay[2] | Cell Line: | Embryonic stem cells | | Concentration: | 1 μM, 3 μM | | Incubation Time: | 24 hours, 72 hours, 120 hours, 168 hours, 216 hours | | Result: | Yields concentration-dependent growth defects in ESCs. |
Cell Proliferation Assay[3] | Cell Line: | M14 and SKMEL-28 cells[3] | | Concentration: | 0.1 μM, 0.5 μM, 1 μM, 2 μM, 5 μM, 10 μM | | Incubation Time: | 24 h | | Result: | Effectively inhibited the growth of both the BRAF mutant melanoma cell lines. |
Western Blot Analysis[3] | Cell Line: | A375 cells | | Concentration: | 10 μM | | Incubation Time: | 24 h | | Result: | Resulted in the upregulation of pro-apoptotic genes. |
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体内研究
(In Vivo) | TP-472 (20 mg/kg; i.p.; three times a week; for 5 weeks) significantly inhibits the subcutaneous tumor growth in melanoma xenograft mouse model[3].
| Animal Model: | NSG mice injected with A375-MA2 cells (male five- to six-week-old)[3] | | Dosage: | 20 mg/kg | | Administration: | i.p.; three times a week; for 5 weeks | | Result: | Significantly inhibited the subcutaneous tumor growth in melanoma xenograft mouse model. |
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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(299.96 mM;ultrasonic and warming and heat to 60℃) 配制储备液 | 1 mM | 2.9996 mL | 14.9979 mL | 29.9958 mL | | 5 mM | 0.5999 mL | 2.9996 mL | 5.9992 mL | | 10 mM | 0.3000 mL | 1.4998 mL | 2.9996 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: ≥ 2.5 mg/mL (7.50 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (7.50 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 (7.50 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (7.50 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。 *以上所有助溶剂都可在本网站选购。
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