Thioridazine-d3 2-Sulfone is the deuterium labeled Thioridazine hydrochloride. Thioridazine hydrochloride, an orally active antagonist of the dopamine receptor D2 family proteins, exhibits potent anti-psychotic and anti-anxiety activities. Thioridazine hydrochloride is also a potent inhibitor of PI3K-Akt-mTOR signaling pathways with anti-angiogenic effect. Thioridazine hydrochloride shows antiproliferative and apoptosis induction effects in various types of cancer cells, with specificity on targeting cancer stem cells (CSCs)[1][2][3][4].
体外研究 (In Vitro)
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
405.59
Formula
C21H23D3N2O2S2
CAS 号
1329652-09-6
中文名称
盐酸硫利达嗪 Sulfone
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.
参考文献
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
[2]. Tschanz JT, et, al. Atypical antipsychotic drugs block selective components of amphetamine-induced stereotypy. Pharmacol Biochem Behav. 1988 Nov;31(3):519-22.
[3]. Mu J, et, al. Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer. Oncol Rep. 2014 May;31(5):2107-14.
[4]. Aguilar-Vega L, et, al. Antibacterial properties of phenothiazine derivatives against multidrug-resistant Acinetobacter baumannii strains. J Appl Microbiol. 2021 Apr 22.
[5]. Kang S, et, al. Thioridazine induces apoptosis by targeting the PI3K/Akt/mTOR pathway in cervical and endometrial cancer cells. Apoptosis. 2012 Sep;17(9):989-97.
[6]. Loehr AR, et, al. Targeting Cancer Stem Cells with Differentiation Agents as an Alternative to Genotoxic Chemotherapy for the Treatment of Malignant Testicular Germ Cell Tumors. Cancers (Basel). 2021 Apr 23;13(9):2045.
Thioridazine hydrochloride, an orally active antagonist of the dopamine receptor D2 family proteins, exhibits potent anti-psychotic and anti-anxiety activities. Thioridazine hydrochloride is also a potent inhibitor of PI3K-Akt-mTOR signaling pathways with anti-angiogenic effect. Thioridazine hydrochloride shows antiproliferative and apoptosis induction effects in various types of cancer cells, with specificity on targeting cancer stem cells (CSCs)[1][2][3][4].
IC50 & Target
serotonin
体外研究 (In Vitro)
Thioridazine (0.01-100 μM; 48 h) reduces the cell viability of NCI-N87 and AGS cells in a concentration-dependent manner[2]. Thioridazine (15 μM; 24 h) reduces cell viability of the cervical (HeLa, Caski and C33A) and endometrial (HEC-1-A and KLE) cancer cells[4]. Thioridazine (1-15 μM; 24-48 h) induces gastric cancer cell death via the mitochondrial apoptosis pathway and mitochondrial pathway[2]. Thioridazine (15 μM; 24 h) modulates the regulation of cell cycle progression by interfering with the PI3K/Akt pathway and induces G1 cell cycle arrest in cervical and endometrial cancer cells [4]. Thioridazine inhibits the growth of antibiotic-sensitive and multidrug-resistant strains of A. baumannii[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.
Cell Proliferation Assay[1]
Cell Line:
NCI-N87 and AGS cells
Concentration:
0.01, 0.1, 0.5, 1, 5, 10, 20, 50, 100 μM
Incubation Time:
48 hours
Result:
Exhibited cytotoxicity in gastric cancer cells.
Western Blot Analysis[1]
Cell Line:
NCI-N87 and AGS cells
Concentration:
1, 5, 10, 15 μM
Incubation Time:
24, 48 hours
Result:
Downregulated the precursors of caspase-9, caspase-8 and caspase-3.
体内研究 (In Vivo)
Thioridazine (25 mg/kg; i.p. every 3 days for 3 weeks) extends the survival of tumor-bearing mice and reduces the number of pluripotent embryonal carcinoma (EC) cells within tumors[5]. Thioridazine (1.0-5.0 mg/kg; s.c.) reduces oral behavior and selectively blocks repetitive head bobbing[1].
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.
Animal Model:
Nude and Rag2KO mice were injected with iPS cells or NT2D1 cells[5]
Dosage:
25 mg/kg
Administration:
I.p. every 3 days for 3 weeks
Result:
Reduced the number of OCT4-expressing cells within malignant teratocarcinomas and extended the survival of tumor-bearing mice. With no effect on fertility.
Clinical Trial
分子量
407.04
Formula
C21H27ClN2S2
CAS 号
130-61-0
中文名称
盐酸硫利达嗪;盐酸硫代利哒;甲硫达嗪盐酸盐;甲硫哒嗪盐酸盐
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Tschanz JT, et, al. Atypical antipsychotic drugs block selective components of amphetamine-induced stereotypy. Pharmacol Biochem Behav. 1988 Nov;31(3):519-22.
[2]. Mu J, et, al. Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer. Oncol Rep. 2014 May;31(5):2107-14.
[3]. Aguilar-Vega L, et, al. Antibacterial properties of phenothiazine derivatives against multidrug-resistant Acinetobacter baumannii strains. J Appl Microbiol. 2021 Apr 22.
[4]. Kang S, et, al. Thioridazine induces apoptosis by targeting the PI3K/Akt/mTOR pathway in cervical and endometrial cancer cells. Apoptosis. 2012 Sep;17(9):989-97.
[5]. Loehr AR, et, al. Targeting Cancer Stem Cells with Differentiation Agents as an Alternative to Genotoxic Chemotherapy for the Treatment of Malignant Testicular Germ Cell Tumors. Cancers (Basel). 2021 Apr 23;13(9):2045.