Chlorpromazine 是一种口服有效的、可透过血脑屏障的抗精神病剂，能有效拮抗D2多巴胺受体和5-HT2A，已广泛用于精神分裂症和其他精神疾病。Chlorpromazine 可通过多种途径发挥抗癌活性，包括抗增殖、诱导自噬和周期停滞 (G2-M 期)、抑制细胞色素 c 氧化酶 (CcO)、抑制肿瘤生长和转移以及抑制肿瘤免疫逃逸等。Chlorpromazine 还能阻断 hNav1.7 通道 (IC50=25.9 μM; 浓度依赖的方式) 和 HERG 钾通道 (IC50=21.6 μM) ，其在止痛以及心律失常方面也具有较好的研究潜力。Chlorpromazine 也能抑制网格蛋白介导的内吞作用。
| 生物活性 | Chlorpromazine is an orally active, blood-brain barrier-transparent antipsychotic agent that effectively antagonisesD2 dopamine receptorsand5-HT2A, which is widely used in schizophrenia and other psychiatric disorders. Chlorpromazine exerts anti-cancer activity through a variety of pathways, including anti-proliferation, induction ofautophagyand cycle arrest (G2-M phase), inhibition ofcytochrome c oxidase(CcO), inhibition of tumour growth and metastasis, and inhibition of tumour immune escape. Chlorpromazine also blocks hNav1.7 channels (IC50=25.9 μM; concentration-dependent) and HERG potassium channels (IC50=21.6 μM), which has potential for analgesic and cardiac arrhythmic studies. Chlorpromazine also can inhibit clathrin-mediated endocytosis[1][2][3][4][5]. |
| IC50& Target | D2 dopamine receptors; 5-HT2A[1][6]. |
体外研究
(In Vitro) | Chlorpromazine (0, 10, 20, 40 μM; 0, 24, 48 h) inhibits growth of U-87MG glioma cells in a dose- and time- dependent manner[2].
Chlorpromazine (20 μM; 0, 12, 24, 48 h) decreases the levels of cyclin A and cyclin B1 in U-87MG glioma cells, 12 h later[2].
Chlorpromazine (20 μM) causes inhibition of cell cycle progression[2].
Chlorpromazine (10 μM; 1 h) significantly suppresses the sEV internalization and dramatically reduces MDSCs in sEV-treated bone marrow cells (MDSCs can significantly suppress the immune cell response, causing immunosuppression in cancer cells)[3].
Chlorpromazine (3, 10, 20, 40, 60 μM) blocks the hNav1.7 current in a concentration-dependent manner[4].
Chlorpromazine blocks HERG potassium channels with an IC50value of 21.6 μM and a Hill coefficient of 1.11[5].
Cell Proliferation Assay[2] | Cell Line: | U-87MG glioma cells | | Concentration: | 0, 10, 20, 40 μM | | Incubation Time: | 0, 24, 48 h | | Result: | Showed anti-proliferative activity in a dose- and time-dependent manner. |
Immunofluorescence[3] | Cell Line: | Bone marrow cells (sEV-treated) | | Concentration: | 10 μM | | Incubation Time: | 1 h | | Result: | Reduced MDSCs and suppressed the sEV internalization. |
Western Blot Analysis[2] | Cell Line: | U-87MG glioma cells | | Concentration: | 20 μM | | Incubation Time: | 0, 12, 24, 48 h | | Result: | Decreased the levels of cyclin A and cyclin B1 12 h later, whereas levels of cyclin D1, proliferating cell nuclear antigen and GAPDH remained unchanged. |
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体内研究
(In Vivo) | Chlorpromazine (20 mg/kg; i.p.; single daily for 7 days) inhibits xenograft tumor growth in nude mouse[2].
| Animal Model: | 5- to 6-week-old athymic nude mice bearing intracranial U-87MG xenograft tumors[2]. | | Dosage: | 20 mg/kg | | Administration: | Injected intraperitoneally; single daily for 7 days | | Result: | Inhibited tumor growth on day 17. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
