Fresolimumab

Fresolimumab
GC 1008, GC1008
UNII-375142VBIA
cas 948564-73-6
Structure

• immunoglobulin G4, anti-(human transforming growth factors beta-1, beta-2 (G-TSF or cetermin) and beta-3), human monoclonal GC-1008 γ4 heavy chain (134-215′)-disulfide with human monoclonal GC-1008 κ light chain, dimer (226-226”:229-229”)-bisdisulfide
• immunoglobulin G4, anti-(transforming growth factor β) (human monoclonal GC-1008 heavy chain), disulfide with human monoclonal GC-1008 light chain, dimer

For Idiopathic Pulmonary Fibrosis, Focal Segmental Glomerulosclerosis,and Cancer
An anti-TGF-beta antibody in phase I clinical trials (2011) for treatment-resistant primary focal segmental glomerulosclerosis.
A pan-specific, recombinant, fully human monoclonal antibody directed against human transforming growth factor (TGF) -beta 1, 2 and 3 with potential antineoplastic activity. Fresolimumab binds to and inhibits the activity of all isoforms of TGF-beta, which may result in the inhibition of tumor cell growth, angiogenesis, and migration. TGF-beta, a cytokine often over-expressed in various malignancies, may play an important role in promoting the growth, progression, and migration of tumor cells.


Fresolimumab (GC1008) is a human monoclonal antibody^[1] and an immunomodulator. It is intended for the treatment of idiopathic pulmonary fibrosis (IPF), focal segmental glomerulosclerosis, and cancer^[2][3] (kidney cancer and melanoma).
It binds to and inhibits all isoforms of the protein transforming growth factor beta (TGF-β).^[2]

History

Fresolimumab was discovered by Cambridge Antibody Technology (CAT) scientists^[4] and was one of a pair of candidate drugs that were identified for the treatment of the fatal condition scleroderma. CAT chose to co-develop the two drugs metelimumab (CAT-192) and fresolimumab with Genzyme. During early development, around 2004, CAT decided to drop development of metelimumab in favour of fresolimumab.^[5]
In February 2011 Sanofi-Aventis agreed to buy Genzyme for US$ 20.1 billion.^[6]
As of June 2011 the drug was being tested in humans (clinical trials) against IPF, renal disease, and cancer.^[7][8] On 13 August 2012, Genzyme applied to begin a Phase 2 clinical trial in primary focal segmental glomerulosclerosis^[9] comparing fresolimumab versus placebo.
As of July 2014, Sanofi-Aventis continue to list fresolimumab in their research and development portfolio under Phase II development.^[10]

References

1 WHO Drug Information
2 National Cancer Institute: Fresolimumab

• 3 Statement On A Nonproprietary Name Adopted By The USAN Council – Fresolimumab
• 4 Grütter, Christian; Wilkinson, Trevor; Turner, Richard; Podichetty, Sadhana; Finch, Donna; McCourt, Matthew; Loning, Scott; Jermutus, Lutz; Grütter, Markus G. (2008-12-23). “A cytokine-neutralizing antibody as a structural mimetic of 2 receptor interactions”. Proceedings of the National Academy of Sciences 105 (51): 20251–20256. doi:10.1073/pnas.0807200106. ISSN 0027-8424. PMC 2600578. PMID 19073914.
• 5 http://www.independent.co.uk/news/business/news/cat-may-abandon-skin-drug-after-trial-results-disappoint-569445.html
• 6 http://www.bbc.co.uk/news/business-12477750
• 7 http://www.genengnews.com/gen-news-highlights/scientists-trigger-white-fat-to-become-brown-fat-like-to-treat-obesty-and-type-2-diabetes/81245389/
• 8 Clinicaltrials.gov for Fresolimumab
• 9 http://clinicaltrials.gov/show/NCT01665391
• 10 http://en.sanofi.com/rd/rd_portfolio/rd_portfolio.aspx

Fresolimumab

Monoclonal antibody
Type	Whole antibody
Source	Human
Target	TGF beta 1, 2 and 3
Clinical data
Legal status	Investigational
Identifiers
CAS Number	948564-73-6
ATC code	None
ChemSpider	none
KEGG	D09620
Chemical data
Formula	C6392H9926N1698O2026S44
Molar mass	144.4 kDa

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Monoclonal antibodies for the immune system
Immune system (“-l(i[m])-“)	Human (“-limu-“) immunosuppression: Abrilumab Adalimumab Anifrolumab Atorolimumab Belimumab Brodalumab Carlumab Dupilumab Durvalumab Eldelumab Fresolimumab Golimumab Lerdelimumab Lirilumab Mavrilimumab Metelimumab Morolimumab Namilumab Oxelumab§ Placulumab Sarilumab Sifalimumab Tabalumab Ulocuplumab Varlilumab immune activation: Ipilimumab Nivolumab Pembrolizumab Tremelimumab Urelumab other: Bertilimumab Zanolimumab Mouse (“-limo-“) Afelimomab Elsilimomab Faralimomab Gavilimomab Inolimomab Maslimomab Nerelimomab Odulimomab Telimomab aritox Vepalimomab Zolimomab aritox Chimeric (“-lixi-“) Basiliximab Clenoliximab Galiximab Gomiliximab Infliximab Keliximab Lumiliximab Priliximab Teneliximab Vapaliximab Humanized (“-lizu-“) immunosuppressive: Aselizumab Apolizumab Benralizumab† Cedelizumab Certolizumab pegol Daclizumab Eculizumab Efalizumab Epratuzumab Erlizumab Etrolizumab Fontolizumab Itolizumab Lampalizumab Ligelizumab Lulizumab pegol Mepolizumab Mogamulizumab Natalizumab Ocrelizumab Omalizumab Ozoralizumab Pascolizumab Pateclizumab Pembrolizumab Pexelizumab Pidilizumab PRO 140† Reslizumab Rontalizumab Rovelizumab Ruplizumab Quilizumab Samalizumab Siplizumab Talizumab Teplizumab Tocilizumab Toralizumab Tregalizumab Vatelizumab Vedolizumab Visilizumab TGN1412§ non-immunosuppressive: Ibalizumab† Chimeric + humanized (“-lixizu-“) Otelixizumab
Interleukin (“-k(i[n])-“)	Human (“-kinu-“) Briakinumab Canakinumab Fezakinumab Fletikumab Guselkumab Secukinumab Sirukumab Tralokinumab Ustekinumab Humanized (“-kizu-“, “-kinzu-“) Anrukinzumab Clazakizumab Enokizumab Gevokizumab Ixekizumab Lebrikizumab Olokizumab Perakizumab Tildrakizumab
Inflammatory lesions (“-les-“)	Mouse (“-leso-“) Besilesomab Fanolesomab‡ Lemalesomab Sulesomab
#WHO-EM ‡Withdrawn from market Clinical trials: †Phase III §Never to phase III v t e Index of the immune system Description Physiology cells autoantigens autoantibodies complement surface antigens IG receptors Disease Allergies Immunodeficiency Immunoproliferative immunoglobulin disorders Hypersensitivity and autoimmune disorders Neoplasms and cancer Treatment Procedures Drugs antihistamines immunostimulants immunosuppressants monoclonal antibodies

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