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

生物活性靶点体外研究体内研究 N-[4-氟-3-(三氟甲基)苯基]-N'-[5-(4-吡啶基)-1,3,4-噻二唑-2-基]脲试剂级价格

CAS号:1430213-30-1
英文名:ML216
中文名: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
CBNumber:CB02715652
分子式:C15H9F4N5OS
分子量:383.32
MOL File:1430213-30-1.mol

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 :powder
颜色 :light orange to dark orange

安全信息

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

N-[4-氟-3-(三氟甲基)苯基]-N'-[5-(4-吡啶基)-1,3,4-噻二唑-2-基]脲性质、用途与生产工艺

生物活性 ML216 (CID-49852229)是一种有效地、选择性地、具有抗肿瘤活性的 DNA unwinding activity of BLM(Bloom’s syndrome protein) 的抑制剂。ML216 抑制解旋酶BLM636-1298和BLMfull-length的IC50值分别为0.97 μM和2.98 μM。
靶点
Target Value
BLM 636-1298
(Cell-free assay) 0.97 μM
BLM full-length
(Cell-free assay) 2.98 μM

体外研究

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.

体内研究

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.