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

• ChemBase ID: 4754
• Molecular Formular: C16H14F3IN2O4
• Molecular Mass: 482.1930396
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzamide
• IUPAC Traditional name: N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzamide
• Synonyms: 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

Database IDs

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

CALCULATED PROPERTIES

JChem

• H Acceptors: 5
• H Donor: 4
• LogD (pH = 5.5): 3.975204
• LogD (pH = 7.4): 3.975191
• Log P: 3.9752042
• Molar Refractivity: 96.136 cm^3
• Polarizability: 36.12947 Å^3
• Polar Surface Area: 90.82 Å^2
• Rotatable Bonds: 7
• Lipinski's Rule of Five: true
• Acid pKa: 11.877684

ALOGPS 2.1

• Log P: 2.64
• LOG S: -4.19
• Solubility (Water): 3.13e-02 g/l

PROPERTIES

Physical Property

• Solubility: DMSO; DMSO: ≥20 mg/mL; Methanol
• Apperance: white to off-white powder; White to Off-White Solid
• Melting Point: 112-114°C
• Optical Rotation: [α]/D -1.8 to -3.0°, c = 1 mg/mL in methanol

Safety Information

• Storage Condition: -20°C; -20°C Freezer, Under Inert Atmosphere
• Storage Warning: IRRITANT
• European Hazard Symbols: Nature polluting (N); Toxic (T)
• German water hazard class: 3
• Risk Statements: 25-48-50
• Safety Statements: 22-36/37/39-61
• TSCA Listed: false
• GHS Pictograms: GHS06; GHS08; GHS09
• GHS Signal Word: Danger
• GHS Hazard statements: H301-H373-H410
• GHS Precautionary statements: P273-P301 + P310-P501
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: MEK

Product Information

• Purity: ≥98% (HPLC); 95%; 95+%
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C16H14F3IN2O4

DETAILS

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.

REFERENCES

• 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)