GDC-0449 (Vismodegib)

保质期 ：2 years

英文名 ：GDC-0449 (Vismodegib)

库存 ：10

供应商 ：上海伟进生物科技有限公司

CAS号 ：879085-55-9

保存条件 ：-20℃

规格 ：5mg

Biological Activity

GDC-0449 (Vismodegib) is the active ingredient marketed under the brand name of Erivedge^® for the treatment of basal-cell carcinoma (BCC), representing the first Hedgehog (Hh) signaling pathway targeting agent to be approved. GDC-0449 is now undergoing clinical trials for other cancers such as medulloblastoma, advanced stomach cancer, metastatic colorectal cancer and pancreatic cancer. [Note: GDC-0449 sold by Gene Operation is for scientific research use only, not for human and veterinary use.]

GDC-0449 (also known as Hh-Antag691, Vismodegib), a benzimidazole derivative, is a potent, cell permeable and synthetic small molecule inhibitor of Hedgehog (Hh) signaling pathway by targeting Smo protein. GDC-0449 exhibits higher affinity for Smo than cyclopamine, completely blocking Shh function at ＞10-fold lower concentrations. However, the concentration required to inhibit cell growth by GDC-0449 is approximately 1000-fold higher than that needed to suppress Shh activity ^[1-2]. GDC-0449 effectively penetrates the blood-brain barrier after oral delivery, blocks Shh pathway and eliminates medulloblastoma in both Ptc1^+/-p53^-/-and Cxcr6 mutant mice. GDC-0449 produces complete tumor regression at doses as low as 12.5 mg/kg BID in a medulloblastoma allograft mouse model that is wholly dependent on the Hh pathway for growth and is currently in human clinical trials ^[2-4]. Plus, GDC-0449 displays markedly antitumor activity in locally advanced or metastatic BCC. The phase I and phase II clinical trials support its efficacy and safety in the future treatment for patients bearing these tumors ^[5-6]. This compound has been found to be a potent inhibitor of two ABC transporters, ABCG2/BCRP (IC₅₀= 1.4 μM) and ABCB1/Pgp (IC₅₀= 3.0 μM), as well as a mild inhibitor of ABCC1/MRP1.The ability of GDC-0449 and related compounds to inhibit two key ABC transporters may contribute to their effectiveness in treating malignancies ^[7].

Chemical Properties

Cas No.: 879085-55-9	M. Wt.: 421.3
Formula: C19H14Cl2N2O3S	Purity: >99%
Synonym: Hh-Antag691, RG-3616, Vismodegib, Erivedge®
Chemical Name: 2-Chloro-N-(4-chloro-3-(pyridine-2-yl)phenyl)-4-(methylsulfonyl)benzamide
Appearance: Off-white to beige solid
Solubility: Soluble in DMSO at 100 mg/ml. Very slightly soluble in water.
Storage: Store solid at -20 ºC for the stability of two years. Following reconstitution, aliquot and freeze at -20 ºC, prevent from multiple freeze/thaw cycles.