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

SKOG102 is a potent OLIG2 inhibitor that is directly engaging OLIG2 and interferes with the ability of OLIG2 to bind DNA. SKOG102 can be used for the research of glioblastoma (GBM)[1].

Research Areas >> Cancer

OLIG2[1]

SKOG102 (0.1-5 μM; 72 h) 抑制人 GBM4 和 GBM8 细胞生长为神经球，IC50 分别为 10.66 和 1.536 μM[1]。 SKOG102 (0.5-5 μM; 12 h) 增加 GBM4 细胞中的 p21 RNA 水平并降低 OMG RNA 水平[1]。 SKOG102 (5 μM; 20 h) 抑制 OLIG2-DNA 结合，并降低 GBM8 细胞中的丝氨酸磷酸化 OLIG2 和总 OLIG2 蛋白水平[1]。

SKOG102 (10-20 mg/kg; i.p.) 抑制小鼠 GBM4 肿瘤的生长[1]。 SKOG102 (5 mg/kg; i.p.) 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]。 Animal Model: NSG mice were inoculated in each flank with GBM4 cells[1] Dosage: 10, 15, and 20 mg/kg; dissolved in solutol:PEG400:water (20%:40%:40%) Administration: Intraperitoneal injection; first 2 weeks (from day 33 to 46) 10 mg/kg, third week (from day 47 to 54) 15 mg/kg, fourth week (from 55 to 66) first 3 days 20 mg/kg, 2 days break, then alternate days from day 60 to 66 Result: Significantly attenuated tumor growth.

[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.  

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