TELOMESTATIN
| 中文名称 | TELOMESTATIN |
|---|---|
| 中文同义词 | 替莫美他汀;化合物 T28942 |
| 英文名称 | telomestatin |
| 英文同义词 | GM 95;SOT 095;(R)-Telomestatin;telomestatin;YVSQVYZBDXIXCC-INIZCTEOSA-N;3,7,11,15,19,23,27-Heptaoxa-31-thia-33,34,35,36,37,38,39,40-octaazanonacyclo[28.2.1.12,5.16,9.110,13.114,17.118,21.122,25.126,29]tetraconta-2(40),4,6(39),8,10(38),12,14(37),16,18(36),20,22(35),24,26(34),28,30(33)-pentadecaene, 4,8-dimethyl-, (1R)- |
| CAS号 | 265114-54-3 |
| 分子式 | C26H14N8O7S |
| 分子量 | 582.50376 |
| EINECS号 | |
| 相关类别 | |
| Mol文件 | 265114-54-3.mol |
| 结构式 |  |
TELOMESTATIN 性质
| 密度 | 2.01±0.1 g/cm3(Predicted) |
|---|---|
| 酸度系数(pKa) | 0.31±0.20(Predicted) |
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Traditional Cytotoxic Agents
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Telomestatin (0-50 μM) promotes or stabilizes the formation of the intramolecular G-quadruplex. At the DNA concentrations of 0.005 and 0.2 µM, EC 50 values of 0.03 µM and 0.53 µM telomestatin are found. In a parallel experiment with the mutated oligonucleotide d[T2AGAG]4, there is no conversion of the mutated sequence to a G-quadruplex structure by telomestatin.Telomestatin (2-10 μM) effects the expression of DN-hTERT on telomerase activity and telomere length, at 10 μM，the expression of DN-hTERT shows a significant reduction of telomerase activity. Additionally, at 2 μM , the terminal restriction fragment (TRF) length of U937 cells shortens progressively from 9.5 to 3.8 kb at population doubling (PD) 20 in U937 cells.Telomestatin (2-5 μM; short-time or long trem) has less effect on normal diploid human fibroblasts and ALT-positive cells.Telomestatin (5 μM; short-time 3 days) exposure has no affect the viability of normal human fibroblasts BJ or IMR-90; however, 5 μM of telomestatin reduces the viability of GM847 cells.Telomestatin (2 μM; long-term 10-50 days) does not significantly change the proliferation rate or viability to that of control cells in BJ or IMR-90 cells and also does not change the proliferation of GM847 cells.
Telomestatin (intraperitoneal injection; 3-15 mg/kg; two times a week; 4 weeks) decreases tumor telomerase activity and inhibits the growth of U937 xenografts. Systemic administrations of 3 mg/kg or 9 mg/kg or 15 mg/kg of telomestatin decreases tumor telomerase activity by 60.2%, 74% and 92.5% compared to control, respectively.
| Animal Model: | Mice model with U937 xenografts |
| Dosage: | 3-15 mg/kg |
| Administration: | Intraperitoneal injection; 3-15 mg/kg; two times a week; 4 weeks |
| Result: | Treated with PBS for 21 days had a mean tumor volume of 1395 mm 3 compared with telomestatin treated with a mean tumor volume of 291 mm 3 .Exhibited no adverse effects (body weight loss, clinical signs or survival).Reduced U937 cells in bone marrow and recovered the normal hematopoiesis in mice. |