Inobrodib (CCS1477) 是一种口服活性的、有效且选择性强的p300/CBP抑制剂。Inobrodib 与 p300 和 CBP 结合，Kd值为 1.3 和 1.7 nM，与 Kd为 222 nM 的 BRD4 相比，具有 170/130 倍的选择性。Inobrodib 抑制前列腺癌细胞系的细胞增殖并降低雄激素受体 (AR) 和 C-MYC 调节的基因表达。
| 生物活性 | Inobrodib (CCS1477) is an orally active, potent, and selective inhibitor of thep300/CBP bromodomain. Inobrodib binds to p300 and CBP withKdvalues of 1.3 and 1.7 nM, respectively, and with 170/130-fold selectivity compared withBRD4with a Kdof 222 nM. CCS1477 inhibits cell proliferation in prostatecancercell lines and decreasesandrogen receptor(AR)- and C-MYC-regulated gene expression[1]. |
| IC50& Target | |
体外研究
(In Vitro) | Inobrodib binding to cellular histones in an in-cell BRET assay gives an IC50 of 19 nM for p300 and 1,060 nM for BRD4. Inobrodib shows potent growth-inhibitory activity in VCaP, 22Rv1, and LNCaP95 (all IC50< 100 nM) that express both AR-FL and AR-V7[1].
Inobrodib (0-3000 nM; 48 hours) reduces expression of AR-regulated genes (KLK2, KLK3, and TMPRSS2) in both 22Rv1 and LNCaP95 cells. Inobrodib also reduces C-MYC protein expression in both 22Rv1 and LNCaP95 cells and AR-V7 protein expression in 22Rv1 cells, without clear impact on AR-FL protein expression in 22Rv1 and LNCaP95 cells. Inobrodib reduces C-MYC mRNA and downstream AR and C-MYC signaling in 22Rv1 and C4-2 cells at 16 hours. Inobrodib regulates AR signaling by affecting the recruitment of CBP, p300, and AR-FL to known AR binding sites, and has the potential to abrogate persistent AR signaling in CRPC[1].
|
体内研究
(In Vivo) | Inobrodib (10-30 mg/kg; oral gavage; 10 or 20 mg/kg daily (QD) or 30 mg/kg every other day (QOD) for 28 days) suppresses growth of a 22Rv1 mouse xenograft model with associated reduction in AR signaling[1].
Inobrodib (20 mg/kg; oral gavage; daily for 8 days) decreases AR and AR-V7 signaling and inhibits growth in a patient- derived model of lethal prostate cancer (NOD/SCID gamma (NSG) male castrated mice)[1].
| Animal Model: | Noncastrated male athymic nude mice[1] | | Dosage: | 10-30 mg/kg | | Administration: | Oral gavage; at 10 or 20 mg/kg daily (QD) or at 30 mg/kg every other day (QOD) for 28 days | | Result: | Affected tumor growth at 10 mg/kg daily, 20 mg/kg daily, and 30 mg/kg every other day. |
|
| 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 : 100 mg/mL(187.06 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.8706 mL | 9.3528 mL | 18.7056 mL | | 5 mM | 0.3741 mL | 1.8706 mL | 3.7411 mL | | 10 mM | 0.1871 mL | 0.9353 mL | 1.8706 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: ≥ 5.25 mg/mL (9.82 mM); Clear solution
此方案可获得 ≥ 5.25 mg/mL (9.82 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 52.5 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%corn oil Solubility: ≥ 5.25 mg/mL (9.82 mM); Clear solution
此方案可获得 ≥ 5.25 mg/mL (9.82 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 52.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 3. 请依序添加每种溶剂： 5% DMSO 40%PEG300 5%Tween-80 50% saline Solubility: ≥ 2.5 mg/mL (4.68 mM); Clear solution 4. 请依序添加每种溶剂： 5% DMSO 95% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (4.68 mM); Clear solution *以上所有助溶剂都可在本网站选购。
|
m.cnreagent.com