Inobrodib (CCS1477) is an orally active, potent, and selective inhibitor of the p300/CBP bromodomain. Inobrodib binds to p300 and CBP with K_d values of 1.3 and 1.7 nM, respectively, and with 170/130-fold selectivity compared with BRD4 with a K_d of 222 nM. CCS1477 inhibits cell proliferation in prostate cancer cell lines and decreases androgen receptor (AR)- and C-MYC-regulated gene expression^[1].

p300/CBP^[1]

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

534.60

C₃₀H₃₂F₂N₄O₃

2222941-37-7

Room temperature in continental US; may vary elsewhere.

DMSO : 100 mg/mL (187.06 mM; Need ultrasonic)

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°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

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。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 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-CD in saline)

  Solubility: ≥ 2.5 mg/mL (4.68 mM); Clear solution

• [1]. Rasool RU, et al. Toppling the HAT to Treat Lethal Prostate Cancer. Cancer Discov. 2021;11(5):1011-1013.