N-{3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl}propane-1-sulfonamide

• ChemBase ID: 72603
• Molecular Formular: C23H18ClF2N3O3S
• Molecular Mass: 489.9221264
• Monoisotopic Mass: 489.07254657
• SMILES: c1(cnc2c(c1)c(c[nH]2)C(=O)c1c(c(ccc1F)NS(=O)(=O)CCC)F)c1ccc(cc1)Cl
• Canonical SMILES: CCCS(=O)(=O)Nc1ccc(c(c1F)C(=O)c1c[nH]c2c1cc(cn2)c1ccc(cc1)Cl)F
• InChI: InChI=1S/C23H18ClF2N3O3S/c1-2-9-33(31,32)29-19-8-7-18(25)20(21(19)26)22(30)17-12-28-23-16(17)10-14(11-27-23)13-3-5-15(24)6-4-13/h3-8,10-12,29H,2,9H2,1H3,(H,27,28)
• InChIKey: GPXBXXGIAQBQNI-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-{3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl}propane-1-sulfonamide
• IUPAC Traditional name: vemurafenib; N-{3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl}propane-1-sulfonamide
• Synonyms: N-[3-[[5-(4-Chlorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]-2,4-difluorophenyl]-1-propanesulfonamide; PLX 4032; RG 7204; Ro 51-85426; Vemurafenib; RG7204; R7204; RO5185426; PLX-4032

Database IDs

• CAS Number: 918504-65-1
• PubChem SID: 162037528
• PubChem CID: 42611257

CALCULATED PROPERTIES

• Acid pKa: 7.1725626
• H Acceptors: 4
• H Donor: 2
• LogD (pH = 5.5): 4.612394
• LogD (pH = 7.4): 4.269431
• Log P: 4.6224833
• Molar Refractivity: 121.9691 cm^3
• Polarizability: 48.621117 Å^3
• Polar Surface Area: 91.92 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: B-Raf

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S1267

Research Area

• Description: Malignant melanoma,Colorectal cancer

Protocol

• Protocol: Kinase Assay ^[1]
• RAF kinase activity measurements: The kinase activities of wild-type RAF and mutants are determined by measuring phosphorylation of biotinylated-BAD protein. For each enzyme (0.01 ng), 20 μL reactions are carried out in 20 mM Hepes (pH 7.0), 10 mM MgCl₂, 1 mM DTT, 0.01% (v/v) Tween-20, 50 nM biotin-BAD protein, and 1 mM ATP at room temperature. Reactions are stopped at 5 min with 5 μL of a solution containing 20 mM Hepes (pH 7.0), 200 mM NaCl, 80 mM EDTA, 0.3% (w/v) bovine serum albumin (BSA). The stop solution also includes phospho-BAD (Ser112) antibody, streptavidin-coated donor beads, and protein A acceptor beads. The antibody and beads are pre-incubated in stop solution in the dark at room temperature for 30 min. The final dilution of antibody is 1/2000 and the final concentration of each bead is 10 μg/mL. The assay plates are incubated at room temperature for one hour and then are read on a PerkinElmer AlphaQuest reader. Mutant activities are the average of two different batches of purified protein assayed in duplicate in three different experiments.
• Protocol: Cell Assay ^[2]
• Cell Lines: MALME-3M, Colo829, Colo38, A375, SK-MEL28, and A2058 cells
• Concentrations: 0–10 μM , dissolved in DMSO
• Incubation Time: 5 days
• Methods: Cellular proliferation is evaluated by MTT assay. Briefly, cells are plated in 96-well microtiter plates at a density of 1000 to 5000 cells per well in a volume of 180 μL. PLX4032 is prepared at 10 times the final assay concentration in media containing 1% DMSO. Twenty-four hours after cell plating, 20 μL of the appropriate dilution of PLX4032 are added to plates in duplicate. The plates are assayed for proliferation 6 days after the cells are plated. Percent inhibition is calculated and the IC50 is determined from the regression of a plot of the logarithm of the concentration versus percent inhibition.
• Protocol: Animal Study ^[2]
• Animal Models: Mice (athymic nude) xenograft models of LOX, Colo829, and A375 cells
• Formulation: Formulated as microprecipitated bulk powder (MBP), suspended at the desired concentration in an aqueous vehicle containing 2% Klucel LF, and adjusted to pH 4 with dilute HCl
• Doses: 12.5 mg/kg–100 mg/kg
• Administration: Oral gavage twice daily

References

• References: [1] Bollag G, et al. Nature, 2010, 467(7315), 596-599.
• References: [2] Yang H, et al. Cancer Res, 2010, 70(13), 5518-5527.
• References: [3] Prahallad A, et al. Nature, 2012, 483(7387), 100-103.
• References: [4] Kumar A, et al. J Mol Biol, 2005, 348(1), 183-193.

Toronto Research Chemicals - V118500

Vemurafenib selective BRAFV600E kinase inhibitor; an antitumor agent. Vemurafenib functions by inhibiting the proliferation and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase and ERK phosphorylation in a panel of tumor cell l

REFERENCES

• Bollag G, et al. Nature, 2010, 467(7315), 596-599.
• Yang H, et al. Cancer Res, 2010, 70(13), 5518-5527.
• Prahallad A, et al. Nature, 2012, 483(7387), 100-103.
• Kumar A, et al. J Mol Biol, 2005, 348(1), 183-193.
• Halaban, R. et al.: Pigm. Cell. Melonoma Res., 23, 190 (2010)
• Yang, H. et al.: Cancer Res., 70, 5518 (2010)
• Comin-Anduix, B. et al.: Clin. Cancer Res., 16, 6040 (2010)