FIT-039 是一种选择性，ATP 竞争性且具有口服活性的CDK9抑制剂，对CKD9/cyclin T1的IC50为 5.8 μM。FIT-039 不抑制其他 CDK 和其他激酶。FIT-039 抑制HSV-1(IC50为 0.69 μM)，HSV-2，人腺病毒和人CMV的复制。FIT-039 是一种有前途的抗病毒剂，可用于抑制耐药性HSV和其他 DNA 病毒。
| 生物活性 | FIT-039 is a selective, ATP-competitive and orally activeCDK9inhibitor with anIC50of 5.8 μM forCKD9/cyclin T1. FIT-039 does not inhibit other CDKs and other kinases. FIT-039 inhibits replication ofHSV-1(IC50of 0.69 μM),HSV-2,human adenovirus, andhumanCMV. FIT-039 is a promising antiviral agent for inhibiting drug-resistantHSVsand otherDNA viruses. |
| IC50& Target[1] | CDK9/cyclinT1 5.8 μM (IC50) | HSV-1 0.69 μM (IC50) | HSV-2 | CMV |
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体外研究
(In Vitro) | FIT-039 (30 μM; 3 hours; HEK293 cells) treatment decreases phosphorylated CTD in the infected or noninfected cells to a level lower than that shown by Flavopiridol. FIT-039 reduces the expression levels of HSV-1 immediate-early genes (IEGs) and early and late genes[1].
FIT-039 inhibits replication of the HSV-1 genome in a dose-dependent manner (EC50and EC80are 0.69 μM and 4.0 μM, respectively)[1].
FIT-039 potently suppresses 8 kinases (GSK3β, PKN1, haspin, p70s6K, DYRK1B, GSK3α, IRR, and DYRK3) other than CDK9 on the 332-kinase panel. These kinases are involved in the replication of various viruses[1].
Western Blot Analysis[1] | Cell Line: | HEK293 cells | | Concentration: | 30 μM | | Incubation Time: | 3 hours | | Result: | Decreased phosphorylated carboxyterminal domain (CTD) in the infected or noninfected cells to a level lower than that shown by Flavopiridol. |
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体内研究
(In Vivo) | Treatment with the FIT-039 ointment twice a day suppresses skin lesions and rescues mice (male BALB/c mice injected with HSV-1) from lethality in a dose-dependent manner. The healing of lesions is observed with 5% to 10% FIT-039 ointment, leading to the complete regression of zosteriform spread on day 10, which is also observed with the 5% ACV ointment[1].
FIT-039 does not affect body weight gain in mice administrated with an overdose of this compound (1000 mg/kg/d) for 14 days, and no changes are observed in biological markers in their blood[1].
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(317.05 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.1705 mL | 15.8524 mL | 31.7048 mL | | 5 mM | 0.6341 mL | 3.1705 mL | 6.3410 mL | | 10 mM | 0.3170 mL | 1.5852 mL | 3.1705 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。-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 40%PEG300 5%Tween-80 45% saline Solubility: 2.5 mg/mL (7.93 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (7.93 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 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.5 mg/mL (7.93 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (7.93 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 25.0 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。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (7.93 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (7.93 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。 *以上所有助溶剂都可在本网站选购。
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