SB-743921 hydrochloride is a potent inhibitor of the mitotic kinesin KSP (Eg5), with a K_i of 0.1 nM.

SB-743921 is a potent inhibitor of Eg5, with a K_i of 0.1 nM^[1]. SB-743921 (1 nM) potently inhibits colony forming cell (CFC) formation of chronic myeloid leukemia (CML) primary cells, but exhibits slight inhibitory activities on the colony-forming ability of normal bone marrow progenitors. SB-743921 (1, 3 nM) induces apoptosis of CML primary CD34 + cells, and shows slight effect on normal CD34 + cells. SB-743921 (2 nM) in combination with imatinib displays additive anti-proliferative effect in KCL22 and CML CD34 + cells. Furthermore, SB-743921 overcomes imatinib resistance in CML cells. SB-743921 (0.5 nM, 1 nM, 3 nM) inhibits MEK/ERK and AKT signaling in CML cells^[2].

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.

SB-743921 has good oral bioavailability and pharmacokinetics and induces complete tumor regression in nude mice bearing lung cancer patient xenografts^[3].

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.

553.52

C₃₁H₃₄Cl₂N₂O₃

940929-33-9

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

DMSO : ≥ 100 mg/mL (180.66 mM)

H₂O : 10 mg/mL (18.07 mM; ultrasonic and warming and heat to 60°C)

* “≥” means soluble, but saturation unknown.

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 (sealed storage, away from moisture)。-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: ≥ 2.5 mg/mL (4.52 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.52 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% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (4.52 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.52 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 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
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (4.52 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.52 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]. Jeffrey R. Jackson, et al. A second generation KSP inhibitor, SB-743921, is a highly potent and active therapeutic in preclinical models of cancer. First AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development, Sep 12-15, 2006.

  [2]. Yin Y, et al. Kinesin spindle protein inhibitor SB743921 induces mitotic arrest and apoptosis and overcomes imatinib resistance of chronic myeloid leukemia cells. Leuk Lymphoma. 2015 Jun;56(6):1813-20.

  [3]. Good JA, et al. Optimized S-trityl-L-cysteine-based inhibitors of kinesin spindle protein with potent in vivo antitumor activity in lung cancer xenograft models. J Med Chem. 2013 Mar 14;56(5):1878-93.

K562 and KCL22 cells are seeded in six-well plates at a number of 5 × 10⁵ in 2 mL RPMI-1640 medium supplemented with 10% FBS in a 5% CO₂ atmosphere at 37°C, and are treated with control (2% DMSO), 50 nM imatinib, 2 nM SB-743921 and 50 nM imatinib + 2 nM SB-743921, respectively. Cell number and viability are determined every 24 h. Results are plotted for live cells against time to generate a growth curve^[2].

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.

The animal experiments are performed with female NMRI nu/nu mice. Tumor fragments are obtained from xenografts in serial passage in nude mice. Mice are randomized to the various groups, and dosing is started when the required number of mice carries a tumor of 50-250 mm³ volume, preferably 80-200 mm³. Vehicle for 1: 10% ethanol, 10% cremophor, 80% D5W (dextrose 5%); vehicle for all other compounds (including SB-743921): 8% DMSO, 2% Tween 80, distilled water (pH 5). All treatments are given intraperitoneally. Vehicle control mice (group 1) are treated with 10 mL/kg vehicle on days 0, 3, 6, 8, 10, 13, 20, 22, 24, 29, 31, 34, 36, 38, 48, 51, 55, 58, 62, 65, and 69^[3].

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]. Jeffrey R. Jackson, et al. A second generation KSP inhibitor, SB-743921, is a highly potent and active therapeutic in preclinical models of cancer. First AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development, Sep 12-15, 2006.

  [2]. Yin Y, et al. Kinesin spindle protein inhibitor SB743921 induces mitotic arrest and apoptosis and overcomes imatinib resistance of chronic myeloid leukemia cells. Leuk Lymphoma. 2015 Jun;56(6):1813-20.

  [3]. Good JA, et al. Optimized S-trityl-L-cysteine-based inhibitors of kinesin spindle protein with potent in vivo antitumor activity in lung cancer xenograft models. J Med Chem. 2013 Mar 14;56(5):1878-93.