BET bromodomain inhibitor 1 is an orally active, selective bromodomain and extra-terminal (BET) bromodomain inhibitor with an IC₅₀ of 2.6 nM for BRD4. BET bromodomain inhibitor 1 binds to BRD2(2), BRD3(2), BRD4(1), BRD4(2), and BRDT(2) with high affinities (K_d values of 1.3 nM, 1.0 nM, 3.0 nM, 1.6 nM, 2.1 nM, respectively). bromodomain inhibitor 1 has anti-cancer activity^[1].

BET bromodomain inhibitor 1 (compound 38; 31.25-125 nM; 24 hours) leads to more pronounced G1-phase cell cycle arrest^[1].
BET bromodomain inhibitor 1 (31.25-500 nM; 6 or 24 hours) is highly effective in inducing dose-dependent inhibition on c-Myc expression and upregulation of p21 levels^[1].
BET bromodomain inhibitor 1 (31.25-125 nM; 6 hours) robustly reduces the expressions of c-Myc, BCL-2, and CDK6^[1].
BET bromodomain inhibitor 1 does not inhibit five cytochrome P450 enzymes (IC₅₀>20 μM)^[1].
BET bromodomain inhibitor 1 demonstrates an excellent selectivity for the BET bromodomain family over other bromodomains, with an ∼1500-fold selectivity for BRD4(1) over EP300 (IC₅₀=3857 nM)^[1].
BET bromodomain inhibitor 1 strongly inhibited the growth of acute myeloid leukemia cell line MV4-11, acute leukemia cell lines Kasumi-1 and RS-4-11, and multiple myeloma cancer cell line MM1.S cells with IC₅₀ values of 2.4, 4.8, 17.6 and 15.1 nM, respectively^[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

BET bromodomain inhibitor 1 (compound 38; 6.25, 12.5 mg/kg; PO; daily ; for 28 days) exhibits stronger antitumor activities and completely inhibits the growth of tumor with a tumor growth inhibition (TGI) of 99.7% at 12.5 mg/kg^[1].
BET bromodomain inhibitor 1 (1 mg/kg; IV) has a T_1/2 of 1.3 and 0.9 hours, a CL of 21.5 and 15.3 mL/min•kg, and a V_ss of 1464 and 782 mL/kg for rats and mouse, respectively^[1].
BET bromodomain inhibitor 1 (3 mg/kg; PO) has a T_1/2 of 3.6 hours, a C_max of 159 ng/mL and an AUC of 884 ng•h/mL for rats^[1].
BET bromodomain inhibitor 1 (1.3 mg/kg; PO) has a T_1/2 of 1.3 hours, a C_max of 399 ng/mL and an AUC of 1710 ng•h/mL for mouse^[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

459.47

C₂₂H₁₉F₂N₃O₄S

2411226-02-1

Room temperature in continental US; may vary elsewhere.

DMSO : 62.5 mg/mL (136.03 mM; ultrasonic and warming and heat to 60°C)

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    90% corn oil

  Solubility: ≥ 2.5 mg/mL (5.44 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.44 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。

• 2.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.08 mg/mL (4.53 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.53 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。

  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

• 3.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.08 mg/mL (4.53 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.53 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 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明

• [1]. Zizhou Li, et al. Discovery of 8-Methyl-pyrrolo[1,2- a]pyrazin-1(2 H)-one Derivatives as Highly Potent and Selective Bromodomain and Extra-Terminal (BET) Bromodomain Inhibitors. J Med Chem. 2020 Apr 23;63(8):3956-3975.