1-(3-fluoro-4-{[2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yl]oxy}phenyl)-3-(2-phenylacetyl)thiourea

• ChemBase编号: 72634
• 分子式: C26H20FN5O2S2
• 平均质量: 517.5977032
• 单一同位素质量: 517.10424513
• SMILES: c1(ccccc1)CC(=O)NC(=S)Nc1ccc(c(c1)F)Oc1c2c(ncc1)cc(s2)c1ncn(c1)C
• Canonical SMILES: S=C(NC(=O)Cc1ccccc1)Nc1ccc(c(c1)F)Oc1ccnc2c1sc(c2)c1ncn(c1)C
• InChI: InChI=1S/C26H20FN5O2S2/c1-32-14-20(29-15-32)23-13-19-25(36-23)22(9-10-28-19)34-21-8-7-17(12-18(21)27)30-26(35)31-24(33)11-16-5-3-2-4-6-16/h2-10,12-15H,11H2,1H3,(H2,30,31,33,35)
• InChIKey: UFICVEHDQUKCEA-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 1-(3-fluoro-4-{[2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yl]oxy}phenyl)-3-(2-phenylacetyl)thiourea
• IUPAC传统名: 1-(3-fluoro-4-{[2-(1-methylimidazol-4-yl)thieno[3,2-b]pyridin-7-yl]oxy}phenyl)-3-(2-phenylacetyl)thiourea
• 别名: MGCD-265

登记号

• CAS号: 875337-44-3
• PubChem SID: 162037559
• PubChem CID: 24901704

理论计算性质

• Acid pKa: 5.1210628
• 质子受体: 3
• 质子供体: 2
• LogD (pH = 5.5): 4.7779
• LogD (pH = 7.4): 4.1694236
• Log P: 4.714878
• 摩尔折射率: 141.5446 cm^3
• 极化性: 56.02342 Å^3
• 极化表面积: 81.07 Å^2
• 可自由旋转的化学键: 6
• 里宾斯基五规则: false

分子性质

理化性质

• 溶解度: DMSO

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: Met; Tie-2; VEGFR

产品相关信息

• 成盐信息: Free Base

详细说明

Selleck Chemicals - S1361

Research Area

• Description: Solid tumours,Non-small cell lung cancer

Biological Activity

• Description: MGCD-265 is a potent, multi-target and ATP-competitive inhibitor of Met, VEGFR1, VEGFR2, VEGFR3, Ron, and Tie2 with IC50 of 1 nM, 3 nM, 3 nM, 4 nM, 2 nM and 7 nM, respectively.
• Targets: Met; VEGFR1; VEGFR2; VEGFR3; Ron; Tie2
• IC50: 1 nM; 3 nM; 3 nM; 4 nM; 2 nM; 7 nM ^[1]
• In Vitro: MGCD-265 is a multi-target inhibitor of receptor tyrosine kinases. MGCD-265 potently inhibits Met, Met^Y1235D, Met^M1250T, VEGFR1, VEGF2, VEGF3, Ron, and Tie2, with IC50 values ranging from 1 nM to 7 nM. ^[1]MGCD-265 inhibits cell proliferation both in c-Met-driven tumor cells (MKN45, MNNG-HOS, and SNU-5) and in non-c-Met-driven tumor cells (HCT116 and MDA-MB-231), with IC50 values of 6 nM–30 nM and 1 μM–3 μM, respectively. In serum starved MKN45 cells, MGCD-265 (40 nM–5 μM) effectively inhibits c-Met phosphorylation and its downstream signaling pathways, including Erk, Akt, Stat3, and Fak. MGCD-265 (6 nM–1 μM) also induces apoptosis in MKN45 cells. ^[2]
• In Vivo: In c-Met-driven or non-c-Met-driven mice xenograft models of MKN45, U87MG, MDA-MB-231, COLO205, and A549 tumor cells, MGCD-265 (20 mg/kg–60 mg/kg) inhibits tumor growth and c-Met signaling. MGCD-265 (40 mg/kg) also downregulates genes involved in angiogenesis, including VEGF and IL-8, both in tumor and plasma of mice with U87MG xenograft. MGCD-265 also inhibits the plasma level of shed-Met. ^[2]
• Clinical Trials: A Phase I clinical trial of MGCD-265 in advanced malignancies has been completed. Currently, MGCD-265, in combination of erlotinib or docetaxel, is under investigation in a Phase I/II clinical trial for advanced malignancies or non-small cell lung cancer.

Protocol

• Protocol: Cell Assay ^[2]
• Cell Lines: HCT116, MDA-MB-231, SNU-5, and MKN45 cells
• Concentrations: 0–5 μM
• Incubation Time: 72 hours
• Methods: Cells are treated with MGCD-265 for 72 hours and cell number is determined as a function of mitochondrial activity, following incubation with MTT for 4 hours.
• Protocol: Animal Study ^[2]
• Animal Models: Mice (CD-1 nude) xenograft models of MKN45, U87MG, MDA-MB-231, COLO205, and A549 cells
• Doses: 20 mg/kg–60 mg/kg
• Administration: Orally

References

• References: [1] Bonfils C. et al. AACR 2012 Annual Meeting, 2012. Abstract 1790.
• References: [2] Beaulieu N. et al. 20th EORTC-NCI-AACR Symposium, 2008.

参考文献

• Bonfils C. et al. AACR 2012 Annual Meeting, 2012. Abstract 1790.
• Beaulieu N. et al. 20th EORTC-NCI-AACR Symposium, 2008.