Olomoucine 是 ATP 竞争性的CDKs 的抑制剂。Olomoucine 是一种嘌呤 (HY-34431) 衍生物，可抑制 CDC2/cyclin B, Cdk2/cyclin a, Cdk2/cyclin E (IC50=7 μM)，CDK/p35 激酶 (IC50=3 μM) 和 ERK1/p44 MAPK 激酶的活性 (IC50=25 μM)。Olomoucine 也具有调节细胞周期和抗黑色素肿瘤的能力。
| 生物活性 | Olomoucine is an ATP competitive inhibitor ofCDKs. Olomoucine is a purine (HY-34431) derivative and inhibits CDC2/cyclin B, Cdk2/cyclin A, Cdk2/cyclin E (bothIC50=7 μM), CDK/p35 kinase (IC50=3 μM) and ERK1/p44 MAP kinase (IC50=25 μM)[1][2]. Olomoucine regulates cell cycle and shows anti-melanin tumor activity[3][4]. |
| IC50& Target[1] | cdk2-cyclin A 7 μM (IC50) | cdk2-cyclin E 7 μM (IC50) | cdk5-p35 25 μM (IC50) |
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体外研究
(In Vitro) | Olomoucine inhibits CDK2 and CDC2 kinases with IC50of 7 μM (CDC2/cyclin B), 7 μM (CDK2/cyclin A), 7 μM (CDK2/cyclin E), 3 Μm (CDK5/p35), and 25μM (ERK1/p44 MAPK), respectively[1].
Olomoucine (0, 5, 10, 15, and 25 μM) is a competitive inhibitor for ATP and as a non-competitive inhibitor for histone H[1].
Olomoucine (0-1000 μM) inhibits DNA synthesis in interleukin-2-stimulated T lymphocytes (CTLL-2 cells) and triggers a Gl arrest similar to interleukin-2 deprivation[2].
Olomoucine (0-100 μM) inhibits Gl/S transition of non-small cell lung cancer cell line MB65 cells[2].
Olomoucine (0-150 μM) inhibits prophase/metaphase transition of Rdditapes oocytes[2].
Olomoucine inhibits tumor cells survival with IC50s of 32.35 μM (dog melanoma), 42.15 μM (mouse B16 melanoma), 82.30 μM (human melanoma), respectively[3].
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体内研究
(In Vivo) | Olomoucine (8 mg/kg; i.v.; once daily; 7 d) induces apoptosis in tumor cells on the 3rd day after treatment without side effects[3].
Cassette dosing was found to overestimate the AUC while underestimating the Cmax compared with single dosing administration[4].
Cassette dosing pharmacokinetics for olomoucine[4]
| Administration | Cmax(nM) | Clobs(l/h) | Vss(obs) (l) | MRTlast(h) | AUCinf(obs) (nM.h) | t1/2(h) | | cassettle | 9208 (0.9) | 1.10 | 0.67 (2.8)/td> | 0.56 | 3030 | 1.03 (0.7) | | single | 7194 (0.6) | 1.18 | 0.52 (2.1)/td> | 0.40 | 2831 | 0.98 (0.7) |
Note: Single agents dosing=50 mg/kg, cassette dosing=16.66 mg/kg.
| Animal Model: | Dog with spontaneous melanoma (oral and maxillofacial tumors)[3] | | Dosage: | 8 mg/kg | | Administration: | Intravenous injection; once daily; for 7 days | | Result: | Induced programmed cell death of cancer cells and resulted in rapid eradication of at least 68% of the tumor cells. |
| Animal Model: | Female Balb C– mice (6 weeks of age; weight of 20 g (±1.2 g))[4] | | Dosage: | 50 mg/kg (single agent) or 16.6 mg/kg combinded with purines (cassette) | | Administration: | Intravenous injection (tail vein); samples taken at 0.25, 0.5, 1, 2, 4, 6, and 24 h post-dosing | | Result: | Resulted faster plasma concentration decreasing with 50 mg/kg (as single agent) than 16.6 mg/kg (as cassette). |
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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 | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 66.67 mg/mL(223.47 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.3519 mL | 16.7594 mL | 33.5188 mL | | 5 mM | 0.6704 mL | 3.3519 mL | 6.7038 mL | | 10 mM | 0.3352 mL | 1.6759 mL | 3.3519 mL |
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以下溶剂前显示的百
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此方案可获得 ≥ 2.5 mg/mL (8.38 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.5 mg/mL (8.38 mM); Suspended solution; Need ultrasonic
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此方案可获得 ≥ 2.5 mg/mL (8.38 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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