PRODUCT INFORMATION
GDC-0449
Item No. 13613
CAS Registry No.:879085-55-9
Formal Name:2-chloro-N-[4-chloro-3(2-pyridinyl)phenyl]-4Cl
(methylsulfonyl)-benzamide
Cl
O
Synonym:Vismodegib
N
MF:C19H14Cl2N2O3S
N
FW:421.3
H
Purity:
≥98%
S
UV/Vis.:
λmax: 262, 344 nm
O
O
Supplied as:
A crystalline solid
Storage:
-20°C
Stability:
As supplied, 2 years from the QC date provided on the Certificate of Analysis, when
stored properly
Laboratory Procedures
GDC-0449 is supplied as a crystalline solid. A stock solution may be made by dissolving the GDC-0449 in the
solvent of choice. GDC-0449 is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide
(DMF), which should be purged with an inert gas. The solubility of GDC-0449 in ethanol is approximately
0.3 mg/ml and approximately 30 mg/ml in DMSO and DMF.
GDC-0449 is sparingly soluble in aqueous buffers. For maximum solubility in aqueous buffers, GDC-0449
should first be dissolved in DMSO and then diluted with the aqueous buffer of choice. GDC-0449 has a
solubility of approximately 0.1 mg/ml in a 1:7 solution of DMSO:PBS (pH 7.2) using this method. We do not
recommend storing the aqueous solution for more than one day.
Description
Smoothened (SMO) is a cell surface receptor that, with Patched, mediates hedgehog signaling to regulate
gene expression through the Gli transcription factors.1 GDC-0449 is a potent antagonist of SMO that
acts in a biphasic manner, with apparent high affinity (Ki = 1.3 nM) and low affinity (Ki = 2.3 µM) binding.2
It suppresses Gli-mediated transcription in Calu-6 tumors with an IC50 value of 13 nM and prevents
hedgehog-dependent medulloblastoma allograft growth in mice.3 GDC-0449 less potently inhibits the
ATP-binding cassette (ABC) proteins ABCG2 and ABCB1 (IC50 = 1.4 and 3.0 µM, respectively), which may
ameliorate drug resistance.4 This compound has potential applications in several forms of cancer, including
basal cell carcinoma.5,6
References
1.
2.
3.
4.
5.
6.
Ruiz-Gómez, A., Molnar, C., Holguín, H., et al. Biochim. Biophys. Acta 1768(4), 901-912 (2007).
Rominger, C.M., Bee, W.-L.T., Copeland, R.A., et al. J. Pharmacol. Exp. Ther. 329(3), 995-1005 (2009).
Robarge, K.D., Brunton, S.A., Castanedo, G.M., et al. Bioorg. Med. Chem. Lett. 19(19), 5576-5581 (2009).
Zhang, Y., Laterra, J., and Pomper, M.G. Neoplasia 11(1), 96-101 (2009).
Scales, S.J. and de Sauvage, F.J. Trends Pharmacol. Sci. 30(6), 303-312 (2009).
Lyseng-Williamson, K.A. and Keating, G.M. Vismodegib. Am. J. Clin. Dermatol. 14(1), 61-64 (2013).
WARNING
THIS PRODUCT IS FOR RESEARCH ONLY - NOT FOR HUMAN OR VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.
SAFETY DATA
This material should be considered hazardous until further information becomes available. Do not ingest, inhale, get in eyes, on skin, or on clothing. Wash thoroughly after
handling. Before use, the user must review the complete Safety Data Sheet, which has been sent via email to your institution.
WARRANTY AND LIMITATION OF REMEDY
Buyer agrees to purchase the material subject to Cayman’s Terms and Conditions. Complete Terms and Conditions including Warranty and Limitation of Liability information
can be found on our website.
Copyright Cayman Chemical Company, 08/19/2016
CAYMAN CHEMICAL
1180 EAST ELLSWORTH RD
ANN ARBOR, MI 48108 · USA
PHONE: [800] 364-9897
[734] 971-3335
FAX: [734] 971-3640
[email protected]
WWW.CAYMANCHEM.COM