N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzamide

• ChemBase编号: 4754
• 分子式: C16H14F3IN2O4
• 平均质量: 482.1930396
• 单一同位素质量: 481.9950396
• SMILES: c1(ccc(cc1F)I)Nc1c(ccc(c1F)F)C(=O)NOC[C@@H](CO)O
• Canonical SMILES: OC[C@H](CONC(=O)c1ccc(c(c1Nc1ccc(cc1F)I)F)F)O
• InChI: InChI=1S/C16H14F3IN2O4/c17-11-3-2-10(16(25)22-26-7-9(24)6-23)15(14(11)19)21-13-4-1-8(20)5-12(13)18/h1-5,9,21,23-24H,6-7H2,(H,22,25)/t9-/m1/s1
• InChIKey: SUDAHWBOROXANE-SECBINFHSA-N

名称和登记号

名称

• IUPAC标准名: N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzamide
• IUPAC传统名: N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzamide
• 别名: N-{[(2R)-2,3-dihydroxypropyl]oxy}-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzamide; (R)-N-(2,3-Dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzamide; PD0325901; N-[(2R)-2,3-Dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-benzamide; PD 0325901; N-[(2R)-2,3-Dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzamide; PD 0325901; PD-0235901; (R)-N-(2,3-Dihydroxypropoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamide

登记号

• CAS号: 391210-10-9
• MDL号: MFCD08435926
• PubChem SID: 99443572; 160968186
• PubChem CID: 9826528

理论计算性质

JChem

• 质子受体: 5
• 质子供体: 4
• LogD (pH = 5.5): 3.975204
• LogD (pH = 7.4): 3.975191
• Log P: 3.9752042
• 摩尔折射率: 96.136 cm^3
• 极化性: 36.12947 Å^3
• 极化表面积: 90.82 Å^2
• 可自由旋转的化学键: 7
• 里宾斯基五规则: true
• Acid pKa: 11.877684

ALOGPS 2.1

• Log P: 2.64
• LOG S: -4.19
• 溶解度: 3.13e-02 g/l

分子性质

理化性质

• 溶解度: DMSO; DMSO: ≥20 mg/mL; Methanol
• 外观: white to off-white powder; White to Off-White Solid
• 熔点: 112-114°C
• 比旋光度: [α]/D -1.8 to -3.0°, c = 1 mg/mL in methanol

安全信息

• 保存条件: -20°C; -20°C Freezer, Under Inert Atmosphere
• 保存注意事项: IRRITANT
• 欧盟危险性物质标志: 环境危害性(Nature polluting) (N); 有毒(Toxic) (T)
• 德国WGK号: 3
• 危险公开号: 25-48-50
• 安全公开号: 22-36/37/39-61
• TSCA收录: false
• GHS危险品标识: GHS06; GHS08; GHS09
• GHS警示词: Danger
• GHS危险声明: H301-H373-H410
• GHS警示性声明: P273-P301 + P310-P501
• 保存温度: 2-8°C

药理学性质

• 作用靶点: MEK

产品相关信息

• 纯度: ≥98% (HPLC); 95%; 95+%
• 成盐信息: Free Base
• Empirical Formula (Hill Notation): C16H14F3IN2O4

详细说明

DrugBank - DB07101

Drug information: experimental

Selleck Chemicals - S1036

Research Area

• Description: Cancer

Protocol

• Protocol: Kinase Assay ^[1]
• In vitro cascade assay: Incorporation of ^32P into myelin basic protein (MBP) is assayed in the presence of a glutathione S-transferase fusion protein containing p44MAP kinase (GST-MAPK) and a glutathione S-transferase protein containing p45MEK (GST-MEK). The assay solution contained 20 mM HEPES, pH 7.4, 10 mM MgCl₂, 1 mM MnCl₂, 1 mM EGTA, 50 mM [gamma-^32P]ATP, 10 mg GST-MEK, 0.5 mg GST-MAPK and 40 mg MBP in a final volume of 100 mL. Reactions are stopped after 20 minutes by addition of trichloroacetic acid and filtered through a GF/C filter mat. ^32P retained on the filter mat is determined using a 1205 Betaplate. PD0325901 is assessed at various dose ranges in order to determine dose response curves.
• Protocol: Cell Assay ^[3]
• Cell Lines: PTC cells
• Concentrations: 0.1 nM- 1 μM
• Incubation Time: 48 hours
• Methods: PTC cells (1 × 10^4) are seeded in 24-well plates with 1 mL of medium for 4 days in a 37 °C incubator. MEK inhibitor PD0325901 at varying concentrations is added to the cells in triplicate on day 0. MTT dissolved in 0.8% NaCl solution at 5 mg/mL is added to each well (0.2 mL) on day 2 to test GI50 or every day for cell growth curves. The cells are incubated at 37 °C for 3 hours with MTT. The liquid is then aspirated from the wells and discarded. Stained cells are dissolved in 0.5 mL of DMSO and their absorption at 570 nm is measured using a Synergy HT multidetection microplate reader. For GI50, cell growth is calculated as 100 × (T ? T₀)/(C ? T₀), where T is the optical density of the wells treated with inhibitors after a 48-hour period, T₀ is the optical density at time zero, and C is the control optical density with DMSO only.
• Protocol: Animal Study ^[3]
• Animal Models: Ncr-nu/nu mice bearing PTC cells
• Formulation: 80 mM citric buffer (pH 7)
• Doses: 20-25 mg/kg
• Administration: Oral gavage

References

• References: [1] Barrett SD, et al. Bioorg Med Chem Lett, 2008, 18(24), 6501-6504.
• References: [2] Judith SS, et al. Proc Amer Assoc Cancer Res.2004,45, Abstract #4003
• References: [3] Henderson YC, et al. Mol Cancer Ther, 2010, 9(7), 1968-1976.

Sigma Aldrich - PZ0162

Legal Information
Sold for research purposes under agreement from Pfizer Inc.
Biochem/physiol Actions
PD 0325901 is a potent MKK1 (MEK1) and MKK2 (MEK2) inhibitor. The Ki is 1.1 and 0.79 nM for MEK1 and MEK2, respectively. PD 0325901 was inactive against a panel of 27 other kinases. PD 0325901 inhibited C26 tumor pERK by 75% when dosed at 25 mg/kg in mice.

Toronto Research Chemicals - P217450

The mitogenic extracellular kinase 1/2 (MEK1/2) inhibitor; has potent activity in a no. of cancer cell types in vitro.

参考文献

• Barrett SD, et al. Bioorg Med Chem Lett, 2008, 18(24), 6501-6504.
• Judith SS, et al. Proc Amer Assoc Cancer Res.2004,45, Abstract #4003
• Henderson YC, et al. Mol Cancer Ther, 2010, 9(7), 1968-1976.
• Davies, H., et al.: Nature, 417, 949 (2002)
• Wellbrock, C., et al.: Cancer Res., 64, 2338 (2002)
• Solit, D., et al.: Cancer Res., 67, 11463 (2002)
• Adjei, A., et al.: J. Clin. Oncol., 26, 2139 (2002)