BAY-299 is a very potent, dual inhibitor with IC₅₀s of 67 nM for BRPF2 bromodomains (BD), 8 nM for TAF1 BD2, and 106 nM for TAF1L BD2.

BAY-299 is a dual inhibitor of the bromodomain and PHD finger (BRPF) family member BRPF2 and the TATA box binding protein-associated factors TAF1 and TAF1L. TR-FRET assays showed that BAY-299 is a potent inhibitor of BRPF2 BD with an IC₅₀ of 67 nM, and a selectivity of 47- and 83-fold over BRPF1 and BRPF3 BDs. The profile of BAY-299 is further confirmed by AlphaScreen assay, where an IC₅₀ of 97 nM and a selectivity of 23- and 25-fold over BRPF1 and BRPF3 BDs are measured. NanoBRET experiments show that the interaction of BRPF2 BD with histones H4 and H3.3 is blocked by BAY-299 with IC₅₀ values of 575 and 825 nM, respectively. For TAF1 BD2, the IC₅₀ values are 970 and 1400 nM, respectively. No inhibitory effect is observed for the interaction between BRPF1 or BRD4 and histone H4 up to 10 μM for BAY-299. BAY-299 inhibits MOLM-13, MV4-11, 769-P, Jurkat, NCI-H526, CHL-1, and 5637 cells proliferation with GI₅₀s of 1060, 2630, 3210, 3900, 6860, 7400, and 7980 nM, respectively^[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.

Studies of the in vivo pharmacokinetic properties of BAY-299 in rat reveal that blood clearance is low (ca. 17% of hepatic blood flow), volume of distribution in steady-state high, terminal half-life long to very long (t_1/2=10 h), and bioavailability high (F=73%). In vivo blood clearance is as anticipated based on rat liver microsome values but lower than expected based on hepatocyte data^[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.

429.47

C₂₅H₂₃N₃O₄

2080306-23-4

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : 25 mg/mL (58.21 mM; Need ultrasonic and warming)

*

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。

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 (5.82 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.82 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。

  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: ≥ 2.5 mg/mL (5.82 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.82 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Bouché L, et al. Benzoisoquinolinediones as Potent and Selective Inhibitors of BRPF2 and TAF1/TAF1L Bromodomains. J Med Chem. 2017 May 11;60(9):4002-4022.

MOLM-13, MV4-11, 769-P, Jurkat, NCI-H526, CHL-1, and 5637 cell lines are treated with BAY-299 while in the logarithmic growth phase, and their viability is determined by AlamarBlue staining^[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.

Rats^[1]
BAY-299 is administered to three male Wistar rats per arm, either intravenously or intragastrally formulated as solutions. BAY-299 is given as i.v. bolus, and blood samples are taken at 2 min, 8 min, 15 min, 30 min, 45 min, 1 h, 2 h, 4 h, 6 h, 8 h, and 24 h after dosing. For pharmacokinetics after intragastral administration, BAY-299 is given intragastrally to fasted rats and blood samples are taken at 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 4 h, 6 h, 8 h, and 24 h after dosing. Blood is collected into lithium-heparin tubes and centrifuged for 15 min at 3000 rpm^[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.

• [1]. Bouché L, et al. Benzoisoquinolinediones as Potent and Selective Inhibitors of BRPF2 and TAF1/TAF1L Bromodomains. J Med Chem. 2017 May 11;60(9):4002-4022.