2-chloro-N-[4-chloro-3-(pyridin-2-yl)phenyl]-4-methanesulfonylbenzamide

• ChemBase ID: 72498
• Molecular Formular: C19H14Cl2N2O3S
• Molecular Mass: 421.29706
• Monoisotopic Mass: 420.01021868
• SMILES: c1(c(cc(cc1)NC(=O)c1ccc(cc1Cl)S(=O)(=O)C)c1ncccc1)Cl
• Canonical SMILES: O=C(c1ccc(cc1Cl)S(=O)(=O)C)Nc1ccc(c(c1)c1ccccn1)Cl
• InChI: InChI=1S/C19H14Cl2N2O3S/c1-27(25,26)13-6-7-14(17(21)11-13)19(24)23-12-5-8-16(20)15(10-12)18-4-2-3-9-22-18/h2-11H,1H3,(H,23,24)
• InChIKey: BPQMGSKTAYIVFO-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-chloro-N-[4-chloro-3-(pyridin-2-yl)phenyl]-4-methanesulfonylbenzamide
• IUPAC Traditional name: vismodegib
• Synonyms: HhAntag691; Vismodegib; GDC-0449(Vismodegib); GDC 0449; 2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)-benzamide; Vismodegib

Database IDs

• CAS Number: 879085-55-9
• PubChem SID: 162037423
• PubChem CID: 24776445

CALCULATED PROPERTIES

• Acid pKa: 10.269497
• H Acceptors: 4
• H Donor: 1
• LogD (pH = 5.5): 3.9222856
• LogD (pH = 7.4): 3.9282904
• Log P: 3.9289317
• Molar Refractivity: 107.812 cm^3
• Polarizability: 42.74018 Å^3
• Polar Surface Area: 76.13 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: ABC; Hedgehog; P-gp

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S1082

Research Area

• Description: Sarcoma,Medulloblastoma, Medulloblastoma,Cancer

Protocol

• Protocol: Cell Assay ^[2]
• Cell Lines: MDCKII cells
• Concentrations: 20 μM
• Incubation Time: 2 hours
• Methods: MDCKII cells are seeded into 24-well plates at a density of 3 × 10^5 cells per well and are allowed to attach. Medium is then changed to that containing different drugs (50 μM VP, 50 μM indomethacin, or 20 μM GDC-0449 in DMSO or DMSO alone as control, and nonfluorescent calcein-AM is added to a final concentration of 1.0 μM and incubated at 37 °C for 2 hours. Cells are then washed twice with Ca^2+, Mg^2+-containing Hank's balanced salt solution buffer and lysed by shaking in 0.01% Triton X-100 in PBS buffer for 1 hour at room temperature or overnight at 4 °C. The lysate is then transferred into 96-well plates, and the fluorescence signal caused by the cell-derived calcein was quantified spectrophotometrically with a SpectraMax M5 Multi-Detection Readerusing an excitation wavelength of 495 nm and an emission wavelength of 515 nm. All manipulations are performed in the dark. All readings are expressed as mean ± SEM normalized to the control.
• Protocol: Animal Study ^[4]
• Animal Models: Ptch(+/-) allograft model, D5123 and 1040830
• Formulation: In 0.5% methyl-cellulose, 0.2% tween-80
• Doses: ~ 100 mg/kg
• Administration: Orally

References

• References: [1] Scales SJ, et al. Trends Pharmacol Sci. 2009, 30(6), 303-312.
• References: [2] Zhang Y, et al. Neoplasia. 2009, 11(1), 96-101.
• References: [3] Tian F, et al. Anticancer Res. 2012, 32(1), 89-94.
• References: [4] Wong H, et al. Clin Cancer Res. 2011, 17(14), 4682-4692.

Toronto Research Chemicals - V674700

Targets the Hedgehog (Hh) pathway. Inhibition of the Hh signaling may be effective in the treatment and prevention of many types of human cancers.

REFERENCES

• Scales SJ, et al. Trends Pharmacol Sci. 2009, 30(6), 303-312.
• Zhang Y, et al. Neoplasia. 2009, 11(1), 96-101.
• Tian F, et al. Anticancer Res. 2012, 32(1), 89-94.
• Wong H, et al. Clin Cancer Res. 2011, 17(14), 4682-4692.
• Gupta, S. et al.: Ther. Advances in Med. Oncology 2,237(2010)