Guanidine,N-(3,4-dichlorophenyl)-N'-[4-[(1-ethyl-3-piperidinyl)amino]-6-methyl-2-pyrimidinyl]-

用途

SKOG102是一种有效的OLIG2抑制剂,它直接与OLIG2结合并干扰OLIG2与DNA结合的能力。SKOG102可用于胶质母细胞瘤(GBM)的研究[1]。

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名称

[ CAS 号 ]:
21062-28-2

[ 英文名 ]:
Guanidine,N-(3,4-dichlorophenyl)-N'-[4-[(1-ethyl-3-piperidinyl)amino]-6-methyl-2-pyrimidinyl]-

[英文别名 ]:

生物活性

[ 描述 ]:

SKOG102是一种有效的OLIG2抑制剂,它直接与OLIG2结合并干扰OLIG2与DNA结合的能力。SKOG102可用于胶质母细胞瘤(GBM)的研究[1]。

[ 相关类别 ]:

研究领域 >> 癌症

[ 靶点 ]

OLIG2[1]

[体外研究]

SKOG102(0.1-5μM；72小时)抑制人国标4和 GBM8标准细胞生长为神经球,国际50分别为 10.66和 1.536μM[1]SKOG102(0.5-5μM；12小时)增加国标4细胞中的 p21 RNA水平并降低 OMG RNA水平[1]。 SKOG102(5μM；20小时)抑制 OLIG2-DNA基因结合,并降低 GBM8标准细胞中的丝氨酸磷酸化奥利2和总奥利2蛋白水平[1]。

[体内研究]

SKOG102(10-20mg/kg；腹腔注射)抑制小鼠国标4肿瘤的生长[1]。 SKOG102(5 mg/kg；腹腔注射)即使在相对较短的时间内也会在肿瘤中积聚,注射小鼠后 4.小时血浆和脑浓度几乎相同[1]。动物模型：NSG小鼠每侧接种GBM4细胞[1]剂量：10、15和20 mg/kg；溶于溶质：PEG400：水(20%:40%:40%)给药：腹膜内注射；前2周(从第33天到第46天)10mg/kg,第3周(从47天到第54天)15mg/kg,第4周(从55天到第66天)前3天20mg/kg,休息2天,然后从第60天到66天交替几天。结果：显著减少肿瘤生长。

[参考文献]

[1]. Tsigelny IF, et, al. Multiple spatially related pharmacophores define small molecule inhibitors of OLIG2 in glioblastoma. Oncotarget. 2017 Apr 4;8(14):22370-22384.

物理化学性质

[ 密度 ]:
1.4g/cm3

[ 沸点 ]:
609.7ºC at 760mmHg

[ 分子式 ]:
C₁₉H₂₅Cl₂N₇

[ 分子量 ]:
422.35500

[ 闪点 ]:
322.5ºC

[ 精确质量 ]:
421.15500

[ PSA ]:
88.96000

[ LogP ]:
4.70340

[ 蒸汽压 ]:
8.31E-15mmHg at 25°C

[ 折射率 ]:
1.67

毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: MF0405000

CHEMICAL NAME :: Guanidine, 1-(3,4-dichlorophenyl)-3-(4-((1-ethyl-3-piperidyl)ami no)-6-methyl-2-pyrimi dinyl)-

CAS REGISTRY NUMBER :: 21062-28-2

LAST UPDATED :: 198204

DATA ITEMS CITED :: 7

MOLECULAR FORMULA :: C19-H25-Cl2-N7

MOLECULAR WEIGHT :: 422.41

WISWESSER LINE NOTATION :: T6N CNJ BMYUM&MR CG DG& D1 FM- CT6NTJ A2

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1041 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 17,75,1974

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 65 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 17,75,1974

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1128 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 17,75,1974

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 53 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 17,75,1974

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 640 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 17,75,1974

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 261 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 17,75,1974

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 28 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 17,75,1974