Chelsea’s unique portfolio of novel antifolate compounds was originally developed by Dr. Gopal Nair, PhD of the University Of South Alabama College Of Medicine, and licensed by the company in 2004. These orally available, metabolically inert, non-metabolized antifolate compounds were engineered to be analogs of methotrexate (MTX). Diseases that may potentially
be treated with antifolates include rheumatoid arthritis, psoriasis, inflammatory
bowel disease, uveitis, ankylosing spondylitis, cancer and other immunological disorders.
MTX, a disease modifying antirheumatic drug and the most widely prescribed treatment for rheumatoid arthritis, is associated with a host of side effects, including gastrointestinal disturbances, renal toxicity and hepatic toxicity, that are thought to be due its metabolic conversion to more toxic and less efficacious metabolites.1,2 Thus, there continues to be an unmet medical need for a safe, well tolerated and efficacious oral therapeutic agent for the treatment of rheumatoid arthritis.2
CH-4051, the lead drug candidate from Chelsea's portfolio of non-metabolized antifolates, is derived from a family of orally available molecules that pre-clinical data suggests potently inhibit several key enzymes that are required for cell proliferation, including dihydrofolate reductase.3 CH-4051 was developed as the L-isomer of CH-1504, another inert antifolate in Chelsea’s portfolio.
CH-1504 has completed a Phase II clinical trial in patients with rheumatoid arthritis. CH-4051 has completed Phase I clinical trials in healthy volunteers. A Phase II clinical trial of CH-4051 in patients with treatment resistant rheumatoid arthritis is currently ongoing. Descriptions of completed clinical trials may be viewed
1. Disease Modification in Rheumatoid Arthritis Market Forecast, Interactive Model. 8 Sep 2011. Datamonitor- Pharmaceuticals & Healthcare. 5 Jan 2012.
2. Castaneda O, Nair MG. Controlled trial of methotrexate versus CH-1504 in the treatment of rheumatoid arthritis. J Rheumatol. 2006 May;33(5):862-4.
3. McGuire JJ, Haile WH. Metabolism-blocked antifolates as potential anti-rheumatoid arthritis agents: 4-amino-4-deoxy-5,8,10-trideazapteroyl-d,l-4'-methyleneglutamic acid (CH-1504) and its analogs. Biochem Pharmacol. 2009 Apr 1;77(7):1161-72.