SY-5609 (CDK7-IN-3) 是一种口服有效的，高选择性，非共价的CDK7抑制剂，KD为 0.065 nM。SY-5609 对 CDK2 (Ki=2600 nM)，CDK9 (Ki=960 nM)，CDK12 (Ki=870 nM) 具有较弱的抑制作用。SY-5609 诱导肿瘤细胞凋亡并具有抗肿瘤活性。
| 生物活性 | SY-5609 (CDK7-IN-3) is an orally active, highly selective, noncovalentCDK7inhibitor with aKDof 0.065 nM. SY-5609 shows poor inhibition onCDK2(Ki=2600 nM),CDK9(Ki=960 nM),CDK12(Ki=870 nM). SY-5609 inducesapoptosisin tumor cells and has antitumor activity[1][2]. |
| IC50& Target[1] | CDK7 0.065 nM (Kd) | CDK2 2600 nM (Ki) | CDK9 960 nM (Ki) | CDK12 870 nM (Ki) |
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体外研究
(In Vitro) | SY-5609 (0.01-10000 nM; 72 hours) demonstrates strong antiproliferative effects in triple negative breast cancer (TNBC) and ovarian (OVA) cancer cells[1].
SY-5609 (100-500 nM; 48, 72 hours) induces apoptosis[1].
SY-5609 (100-500 nM; 48 hours) induces G2/M cell cycle arrest in HCC70 cells[1].
SY-5609 (25-500 nM; 6-48 hours) results in inhibition of the phosphorylation of CDK2 at Thr160 via loss of CAK function for 24 and 48 h[1].
SY-5609 (compound 101; 126.4 pM-4 μM; 72 hours) has an EC50of 5.6 nM in HCC70 cell line[2].
Cell Proliferation Assay[1] | Cell Line: | HCC70, MDA-MB453, COV504, A2780, OVCAR3, CAOV3 cells | | Concentration: | 0.01-10000 nM | | Incubation Time: | 72 hours | | Result: | Demonstrated strong antiproliferative effects with IC50of 1-6 nM. |
Apoptosis Analysis[1] | Cell Line: | HCC70, MDA-MB-468, CAOV3 and OVCAR3 cells | | Concentration: | 100, 250, 500 nM | | Incubation Time: | 48 and 72 hours | | Result: | Induced apoptosis. |
Cell Cycle Analysis[1] | Cell Line: | HCC70 cells | | Concentration: | 100, 250, 500 nM | | Incubation Time: | 48 hours | | Result: | Induced G2/M cell cycle arrest. |
Western Blot Analysis[1] | Cell Line: | HCC70 cells | | Concentration: | 25, 50, 100, 250, 500 nM | | Incubation Time: | 6, 24, 48 hours | | Result: | Resulted in inhibition of the phosphorylation of CDK2 at Thr160 via loss of CAK function for 24 and 48 h. |
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体内研究
(In Vivo) | SY-5609 (2 mg/kg/day; orally; for 21 days) induces tumor regression over the 21-day dosing period[1].
Daily oral dosing of 2 mg/kg SY-5609 in mice provided a plasma exposure of 261.28 ng h/mL with a Cmaxof 50.67 ng/mL (103 nM) and an elimination half-life of 3.33 h[1].
| Animal Model: | Six-to-eight-week-old Balb/c nude female mice with HCC70 cell line[1] | | Dosage: | 2 mg/kg | | Administration: | Orally; daily; for 21 days | | Result: | Induced tumor regression over the 21-day dosing period and was well tolerated. No regrowth of tumor was observed out to day 28. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, stored under nitrogen *In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen) |
| 溶解性数据 | In Vitro: DMSO : 40 mg/mL(81.56 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.0389 mL | 10.1945 mL | 20.3890 mL | | 5 mM | 0.4078 mL | 2.0389 mL | 4.0778 mL | | 10 mM | 0.2039 mL | 1.0195 mL | 2.0389 mL |
*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℃, 6 months; -20℃, 1 month (stored under nitrogen)。-80℃ 储存时，请在 6 个月内使用，-20℃ 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 90% (20%SBE-β-CDin saline) Solubility: 4 mg/mL (8.16 mM); Suspended solution; Need ultrasonic
此方案可获得 4 mg/mL (8.16 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 40.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 2. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 4 mg/mL (8.16 mM); Clear solution
此方案可获得 ≥ 4 mg/mL (8.16 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 40.0 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： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (5.10 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.10 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。 *以上所有助溶剂都可在本网站选购。
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