1430213-30-1
基本信息
N-[4-氟-3-(三氟甲基)苯基]-N'-[5-(4-吡啶基)-1,3,4-噻二唑-2-基]脲
CS-1561
CID49852229
CID-49852229
CID 49852229
ML216(CID4985229)
ML216(CID-49852229)
ML 216
ML-216
CID-49852229
CID49852229
CID 49852229
1-[4-Fluoro-3-(trifluoromethyl)phenyl]-3-[5-(4-pyridinyl)-1,3,4-t hiadiazol-2-yl]ure
N-[4-Fluoro-3-(trifluoromethyl)phenyl]-N'-[5-(4-pyridinyl)-1,3,4-thiadiazol-2-yl]urea
物理化学性质
| 密度 | 1.583±0.06 g/cm3(Predicted) |
| 储存条件 | 2-8°C |
| 溶解度 | DMSO:29.0(Max Conc. mg/mL);75.65(Max Conc. mM) |
| 酸度系数(pKa) | 6.40±0.50(Predicted) |
| 形态 | 粉末 |
| 颜色 | 浅橙色至深橙色 |
安全数据
| 危险性符号(GHS) |  GHS06 |
| 警示词 | 危险 |
| 危险性描述 | H301-H413 |
| 防范说明 | P273-P301+P310+P330 |
| 危险品标志 | T |
| 危险类别码 | 25 |
| 安全说明 | 45 |
| 危险品运输编号 | UN 2811 6.1 / PGIII |
| WGK Germany | 3 |
常见问题列表
| Target | Value |
|
BLM 636-1298
(Cell-free assay) | 0.97 μM |
|
BLM full-length
(Cell-free assay) | 2.98 μM |
ML216 (12.5-50 µM; 24-72 hours; PSNG5 and PSNG13cells) treatment inhibits the proliferation of PSNF5 cells in a concentration-dependent manner, but not of PSNG13 cells.
ML216 treatment leads to a statistically significant increase in the frequency of sister chromatid exchanges (SCEs) in PSNF5 cells, but not in PSNG13 cells.
ML216 increases the sensitivity of PSNF5 cells to aphidicolin but has no sensitizing effect on isogenic PSNG13 cells devoid of BLM.
ML216 inhibits both the full length WRN (
IC
50
of 5 μM) and a truncated WRN
500-946
(
IC
50
of 12.6 μM), with the former being 2.5-fold more sensitive to inhibition. BLM is a little more sensitive than WRN to inhibition by ML216 (1.7-fold based on
IC
50
values). Despite the detectable inhibition of WRN by ML216, this compound appears selective for BLM in human cells. ML216 inhibits proliferation of WRN
+
and WRN
−
cells equally well, and similarly sensitized both cell types to aphidicolin.
Cell Proliferation Assay
| Cell Line: | PSNG5 and PSNG13cells |
| Concentration: | 12.5 μM or 50 µM |
| Incubation Time: | 24 hours, 48 hours, 72 hours |
| Result: | Inhibited the proliferation of PSNF5 cells, but not of PSNG13 cells, and did so in a concentration-dependent manner. |
Although ML216 inhibits unwinding by the sequence-related BLM and WRN helicases similarly in vitro, the apparent dependence on BLM for ML216 to exert its biological effects in human cells suggests BLM specificity for the drug’s mechanism of action in vivo. A co-crystal structure of BLM in complex with inhibitor would be informative. Cellular cues in vivo may induce a specific conformation of WRN that makes it resistant to ML216.