WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 203500
CAS#: 879085-55-9
Description: Vismodegib, also known as GDC-0449 or RG3616, is a hedgehog antagonist, is also a n orally bioavailable small molecule with potential antineoplastic activity. Hedgehog antagonist GDC-0449 targets the Hedgehog signaling pathway, blocking the activities of the Hedgehog-ligand cell surface receptors PTCH and/or SMO and suppressing Hedgehog signaling.
MedKoo Cat#: 203500
Name: Vismodegib
CAS#: 879085-55-9
Chemical Formula: C19H14Cl2N2O3S
Exact Mass: 420.01022
Molecular Weight: 421.3
Elemental Analysis: C, 54.17; H, 3.35; Cl, 16.83; N, 6.65; O, 11.39; S, 7.61
Synonym: GDC0449, GDC 0449, GDC-0449, RG3616, RG 3616, RG-3616, Vismodegib, Erivedge
IUPAC/Chemical Name: 2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide
InChi Key: BPQMGSKTAYIVFO-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: O=C(NC1=CC=C(Cl)C(C2=NC=CC=C2)=C1)C3=CC=C(S(=O)(C)=O)C=C3Cl
Appearance: White solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Vismodegib (GDC-0449) is a hedgehog pathway inhibitor with an IC50 of 3 nM. |
| In vitro activity: | Cell proliferation, apoptosis and the expression of EMT (epithelial mesenchymal transition) related genes for three prostate cancer cell lines were evaluated; androgen-dependent LNCaP and independent C4-2B and PC-3 in the presence of vismodegib in vitro. Vismodegib significantly inhibited cell proliferation and induced cell apoptosis in all cell lines in vitro (p<0.05). The results indicate that vismodegib inhibited cell proliferation via apoptosis and also suppressed EMT. Reference: Anticancer Res. 2020 Sep;40(9):5107-5114. https://ar.iiarjournals.org/content/40/9/5107.long |
| In vivo activity: | The effects of the SMO (Smoothened) antagonist, vismodegib, were investigated in the rat MPM (malignant pleural mesothelioma) model to elaborate the role of Hh (Hedgehog) signaling. Vismodegib was administered and six days later, it was observed that tumor volume measured by MRI was significantly reduced in the treated group compared with control (3-fold difference, P = 0.03; Fig. 3B). Consistently, significant reduction in macroscopic tumor volume (P = 0.03) of the treated group was detected (Fig. 3D). Tumor growth monitored by BLI (bioluminescence) seems to be reduced in the treated group compared with control (see images in Fig. 3E). Reference: Mol Cancer Ther. 2016 May;15(5):1095-105. https://mct.aacrjournals.org/content/15/5/1095.long |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 50.0 | 118.68 |
The following data is based on the product molecular weight 421.3 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Meerang M, Bérard K, Felley-Bosco E, Lauk O, Vrugt B, Boss A, Kenkel D, Broggini-Tenzer A, Stahel RA, Arni S, Weder W, Opitz I. Antagonizing the Hedgehog Pathway with Vismodegib Impairs Malignant Pleural Mesothelioma Growth In Vivo by Affecting Stroma. Mol Cancer Ther. 2016 May;15(5):1095-105. doi: 10.1158/1535-7163.MCT-15-0583. Epub 2016 Feb 2. PMID: 26839306. 2. Ishii A, Shigemura K, Kitagawa K, Sung SY, Chen KC, Yi-Te C, Liu MC, Fujisawa M. Anti-tumor Effect of Hedgehog Signaling Inhibitor, Vismodegib, on Castration-resistant Prostate Cancer. Anticancer Res. 2020 Sep;40(9):5107-5114. doi: 10.21873/anticanres.14514. PMID: 32878799. |
| In vitro protocol: | 1. Ishii A, Shigemura K, Kitagawa K, Sung SY, Chen KC, Yi-Te C, Liu MC, Fujisawa M. Anti-tumor Effect of Hedgehog Signaling Inhibitor, Vismodegib, on Castration-resistant Prostate Cancer. Anticancer Res. 2020 Sep;40(9):5107-5114. doi: 10.21873/anticanres.14514. PMID: 32878799. |
| In vivo protocol: | 1. Meerang M, Bérard K, Felley-Bosco E, Lauk O, Vrugt B, Boss A, Kenkel D, Broggini-Tenzer A, Stahel RA, Arni S, Weder W, Opitz I. Antagonizing the Hedgehog Pathway with Vismodegib Impairs Malignant Pleural Mesothelioma Growth In Vivo by Affecting Stroma. Mol Cancer Ther. 2016 May;15(5):1095-105. doi: 10.1158/1535-7163.MCT-15-0583. Epub 2016 Feb 2. PMID: 26839306. 2. Ishii A, Shigemura K, Kitagawa K, Sung SY, Chen KC, Yi-Te C, Liu MC, Fujisawa M. Anti-tumor Effect of Hedgehog Signaling Inhibitor, Vismodegib, on Castration-resistant Prostate Cancer. Anticancer Res. 2020 Sep;40(9):5107-5114. doi: 10.21873/anticanres.14514. PMID: 32878799. |
1: Poggi L, Kolesar JM. Vismodegib for the treatment of basal cell skin cancer. Am J Health Syst Pharm. 2013 Jun 15;70(12):1033-8. doi: 10.2146/ajhp120311. Review. PubMed PMID: 23719880.
2: Dubey AK, Dubey S, Handu SS, Qazi MA. Vismodegib: the first drug approved for advanced and metastatic basal cell carcinoma. J Postgrad Med. 2013 Jan-Mar;59(1):48-50. Review. PubMed PMID: 23525058.
3: Cirrone F, Harris CS. Vismodegib and the hedgehog pathway: a new treatment for basal cell carcinoma. Clin Ther. 2012 Oct;34(10):2039-50. doi: 10.1016/j.clinthera.2012.08.011. Epub 2012 Oct 1. Review. PubMed PMID: 23036338.
4: Amaria RN, Bowles DW, Lewis KD, Jimeno A. Vismodegib in basal cell carcinoma. Drugs Today (Barc). 2012 Jul;48(7):459-67. doi: 10.1358/dot.2012.48.7.1808490. Review. PubMed PMID: 22844657.
5: Keating GM. Vismodegib: in locally advanced or metastatic basal cell carcinoma. Drugs. 2012 Jul 30;72(11):1535-41. doi: 10.2165/11209590-000000000-00000. Review. PubMed PMID: 22788238.
6: De Smaele E, Ferretti E, Gulino A. Vismodegib, a small-molecule inhibitor of the hedgehog pathway for the treatment of advanced cancers. Curr Opin Investig Drugs. 2010 Jun;11(6):707-18. Review. PubMed PMID: 20496266.
The Hedgehog signaling pathway plays an important role in tissue growth and repair; aberrant constitutive activation of Hedgehog pathway signaling and uncontrolled cellular proliferation may be associated with mutations in the Hedgehog-ligand cell surface receptors PTCH and SMO.
