Vismodegib

Chemical compound

EU EMA: by INN
US FDA: Vismodegib

Pregnancy
category

AU: X (High risk)^[1]

Routes of
administrationBy mouthATC code

L01XJ01 (WHO)

AU: S4 (Prescription only)^[1]
CA: ℞-only
UK: POM (Prescription only)
US: WARNING^[2]Rx-only^[3]
EU: Rx-only

Pharmacokinetic dataBioavailability31.8%Protein binding>99%Metabolism<2% metabolised by CYP2C9, CYP3A4, CYP3A5Elimination half-life4 days (continuous use),
12 days (single dose)ExcretionFecal (82%), Urinary (4.4%)Identifiers

IUPAC name

2-Chloro-N-(4-chloro-3-pyridin-2-ylphenyl)-4-methylsulfonylbenzamide

CAS Number

879085-55-9

PubChem CID

24776445

IUPHAR/BPS

6975

DrugBank

DB08828

ChemSpider

23337846

UNII

25X868M3DS

KEGG

D09992

ChEBI

CHEBI:66903^Y

ChEMBL

ChEMBL473417

CompTox Dashboard (EPA)

DTXSID40236689

ECHA InfoCard100.234.019

Chemical and physical dataFormulaC₁₉H₁₄Cl₂N₂O₃SMolar mass421.29 g·mol⁻¹3D model (JSmol)

Interactive image

SMILES

CS(=O)(=O)C1=CC(=C(C=C1)C(=O)NC2=CC(=C(C=C2)Cl)C3=CC=CC=N3)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)
Key:BPQMGSKTAYIVFO-UHFFFAOYSA-N

Vismodegib, sold under the brand name Erivedge, is a medication used for the treatment of basal-cell carcinoma (BCC).^[3] The approval of vismodegib on January 30, 2012, represents the first Hedgehog signaling pathway targeting agent to gain U.S. Food and Drug Administration (FDA) approval.^[4] The drug is also undergoing clinical trials for metastatic colorectal cancer, small-cell lung cancer, advanced stomach cancer, pancreatic cancer, medulloblastoma and chondrosarcoma as of June 2011^[update].^[5] The drug was developed by the biotechnology/pharmaceutical company Genentech.^[4]

Indication

Vismodegib is indicated for people with basal-cell carcinoma (BCC) which has metastasized to other parts of the body, relapsed after surgery, or cannot be treated with surgery or radiation.^[4]^[6]

Mechanism of action

The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the Hedgehog signaling pathway.^[5] SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway.^[7] This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas.^[8]

Side effects

In clinical trials, common side effects included gastrointestinal disorders (nausea, vomiting, diarrhoea, constipation), muscle spasms, fatigue, hair loss, and dysgeusia (distortion of the sense of taste).^[3]

Development

Vismodegib has undergone several promising phase I and phase II clinical trials for its use in treating medulloblastoma.^[9]

References

^ ^a ^b "Erivedge® (vismodegib)". Australian Prescribing Information, Australian Register of Therapeutic Goods (ARTG). Roche Products Pty Limited. 17 November 2022.
^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
^ ^a ^b ^c "Erivedge- vismodegib capsule". DailyMed. U.S. National Library of Medicine. 9 April 2019. Retrieved 8 January 2023.
^ ^a ^b ^c "FDA approves Erivedge (vismodegib) capsule, the first medicine for adults with advanced basal cell carcinoma". Roche. 30 January 2012. Retrieved 9 August 2020.
^ ^a ^b "Vismodegib". Molecule of the Month. Prous Science. June 2011. Archived from the original on 27 September 2011.
^ Lacroix M (2014). Targeted Therapies in Cancer. Hauppauge, NY: Nova Sciences Publishers. ISBN 978-1-63321-687-7. Archived from the original on 2015-06-26. Retrieved 2014-07-13.
^ "Vismodegib (GDC-0449) Smoothened Inhibitor". BioOncology. Genentech. Archived from the original on 4 June 2011.
^ Spreitzer H (4 July 2011). "Neue Wirkstoffe – Vismodegib". Österreichische Apothekerzeitung (in German) (14/2011): 10.
^ Li Y, Song Q, Day BW (July 2019). "Phase I and phase II sonidegib and vismodegib clinical trials for the treatment of paediatric and adult MB patients: a systemic review and meta-analysis". Acta Neuropathologica Communications. 7 (1): 123. doi:10.1186/s40478-019-0773-8. PMC 6668073. PMID 31362788.

External links

"Vismodegib". Drug Information Portal. U.S. National Library of Medicine.

Targeted cancer therapy / antineoplastic agents (L01)

CI monoclonal antibodies ("-mab")

Receptor tyrosine kinase	ErbB: HER1/EGFR (Cetuximab Panitumumab) HER2/neu (Pertuzumab, Trastuzumab (+hyaluronidase) Trastuzumab emtansine Trastuzumab deruxtecan)
Others for solid tumors	EpCAM (Catumaxomab Edrecolomab) VEGF-A (Bevacizumab)
Leukemia/lymphoma	lymphoid: CD3 (Glofitamab, Elranatamab, Mosunetuzumab), CD20 (Glofitamab Ibritumomab Mosunetuzumab Obinutuzumab Ofatumumab Rituximab Tositumomab), CD30 (Brentuximab), CD52 (Alemtuzumab) myeloid: CD33 (Gemtuzumab ozogamicin)
Other	Amivantamab Atezolizumab Avelumab Belantamab mafodotin Bermekimab Blinatumomab Cemiplimab Daratumumab Dinutuximab beta Dostarlimab Durvalumab Elotuzumab Enfortumab vedotin Epcoritamab Inotuzumab ozogamicin Ipilimumab Isatuximab Loncastuximab tesirine Mirvetuximab soravtansine Mogamulizumab Moxetumomab pasudotox Naxitamab Necitumumab Nivolumab Olaratumab Oportuzumab monatox Pembrolizumab Polatuzumab vedotin Prolgolimab Ramucirumab Retifanlimab Sabatolimab Sacituzumab govitecan Serplulimab Sugemalimab Tafasitamab Talquetamab Tarlatamab Teclistamab Tislelizumab Tisotumab vedotin Toripalimab Tremelimumab

Tyrosine kinase inhibitors ("-nib")

Receptor tyrosine kinase	ErbB: HER1/EGFR (Afatinib Brigatinib Dacomitinib Erlotinib Gefitinib Icotinib Mobocertinib Olmutinib Osimertinib Rociletinib Vandetanib) HER1/EGFR and HER2/neu Lapatinib Neratinib Tucatinib RTK class III: C-kit and PDGFR (Avapritinib Axitinib Masitinib Pazopanib Ripretinib Sorafenib Sunitinib Toceranib) FLT3 (Lestaurtinib, Gilteritinib (AXL, ALK, LTK)) VEGFR Axitinib Cediranib Fruquintinib Lenvatinib Nintedanib Pazopanib Regorafenib Semaxanib Sorafenib Sunitinib Tivozanib Toceranib Vandetanib ALK Alectinib Brigatinib Ceritinib RET inhibitors: Entrectinib (ALK, ROS1, NTRK), Futibatinib (FGFR2), Infigratinib, Larotrectinib (NTRK), Pemigatinib (FGFR), Pralsetinib, Repotrectinib (ROS1, TRK, ALK), Selpercatinib (VEGFR, FGFR), Vandetanib (VEGFR, EGFR). c-MET inhibitors: Cabozantinib (VEGFR), Capmatinib, Crizotinib (ALK)
Non-receptor	bcr-abl Asciminib Bosutinib Dasatinib Imatinib Nilotinib Ponatinib Radotinib Src (Bosutinib Dasatinib) Janus kinase Baricitinib Fedratinib Filgotinib Lestaurtinib Momelotinib Pacritinib Ruxolitinib MAP2K Binimetinib Cobimetinib Selumetinib Trametinib EML4-ALK Crizotinib Entrectinib Lorlatinib Bruton's Acalabrutinib Ibrutinib Pirtobrutinib Zanubrutinib

Receptor tyrosine kinase