THZ2 is a potent and selective CDK7 inhibitor with an IC₅₀ of 13.9 nM.

THZ2 selectively targets CDK7 and potently inhibits the growth of triple-negative but not ER/PR⁺ breast cancer cells. THZ2 at low nanomolar doses also efficiently suppresses the clonogenic growth of TNBC cells with IC₅₀ of appr 10 nM. THZ2 induces apoptotic cell death in triple-negative but not ER/PR⁺ breast cancer cells or normal human cells^[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.

THZ2 (10 mg/Kg) markedly reduces the growth rate of tumors in mice and demonstrates an anti-tumor activity. Compared to vehicle-treated tumors, tumor tissues isolated from mice treated with THZ2 has reduced proliferation and increased apoptosis, as indicated by immunostaining against Ki67 and cleaved Caspase 3 respectively. THZ2 in NOD-SCID mice leads to reduced body weight, suggesting that THZ2 mayt be less well-tolerated in this particular mouse strain^[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.

566.05

C₃₁H₂₈ClN₇O₂

1604810-84-5

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 : 21.67 mg/mL (38.28 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。

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: ≥ 2.17 mg/mL (3.83 mM); Clear solution

  此方案可获得 ≥ 2.17 mg/mL (3.83 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 21.7 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: ≥ 2.17 mg/mL (3.83 mM); Clear solution

  此方案可获得 ≥ 2.17 mg/mL (3.83 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 21.7 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Wang Y, et al. CDK7-Dependent Transcriptional Addiction in Triple-Negative Breast Cancer. Cell. 2015 Sep 24;163(1):174-186.

For 96-well plate assay, cells are plated at the density of 2000 cells per well, and on the next day treated with THZ1 or THZ2 of various concentrations. After 48-hour incubation, cells are fixed and stained with crystal violet. The staining is then extracted by adding each well with 10% acetic acid, with absorbance measured at 590 nm with 750 nm as a reference.

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.

Mice: Nude mice (CrTac:NCr-Foxn1nu) are γ-irradiated with a single dose of 400 rads six hours before transplantation of cells. Breast cancer cells are harvested and resupended in 40% Matrigel-Basement Membrane Matrix, LDEV-free, and then injected (100 μL per site) into the fourth pair of mammary fat pads of mice. Tumors are measured in two dimensions by using manual calipers. Tumor volume is calculated using the formula: V=0.5× length × width × width. Animal with tumor established (mean tumor volume of appr 200 mm³) are randomLy divided into two groups, which are then treated with vehicle (10% DMSO in D5W, 5% dextrose in water) or THZ2 (3 mg/mL, prepared in vehicle solutions) at the dose of 10 mg/kg intraperitoneally twice daily. Tumor volume is measure every 2-3 days. Upon harvesting tumors, tumors are cut into half, with one half fixed in formalin overnight and then in 70% ethanol for histopathology analysis, and the other half snap frozen in liquid nitrogen for immunoblotting.

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]. Wang Y, et al. CDK7-Dependent Transcriptional Addiction in Triple-Negative Breast Cancer. Cell. 2015 Sep 24;163(1):174-186.