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Small Molecule Inhibitors of TNF-a (10 GB 44O7 3ID8)
A London-based university has identified an off-target effect of a marketed, small molecule anti-depressant, which inhibits TNF-a (Tissue Necrosing Factor) production by blocking TLR-8 (Toll Like Receptor-8). This work demonstrates that TLR-8 is a potential new target for RA (Rheumatoid Arthritis) & the researchers are developing analogues which retain the anti-inflammatory action without sedative effects. The researchers are now seeking a partner to further test, develop & market the compound.
Country: United Kingdom
Type: OFFER
Date: 21.10.2010
Background:
Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to a progressive decline in joint function with a decreased life expectancy. RA is characterized by the proliferation and neovascularisation of synovial tissue and it is the most common autoimmune disease effecting approximately 0.5-1% of the population. At present, steroids such as dexamethasone and methyl-prednisolone, are widely used in the treatment of RA. While treatment with steroids can be effective, there are a number of serious side effects associated with long-term use such as osteoporosis and hypertension.
New and alternative treatments currently used for RA are biologicals (e.g. antibodies and soluble receptors), disease modifying anti-rheumatic drugs (DMARDS) and non-steroidal anti-inflammatory drugs (NSAIDs). However, these drug classes also suffer from disadvantages. NSAIDs have proven to help relieve the pain associated with RA; however they do not protect against disease progression. Although DMARDs help to slow disease progression, they are associated with toxicity. The most widely used DMARD, methotrexate has side effects such as skin reactions, damage to liver, kidney, lungs and gastrointestinal tract and infections such as pneumonia. Biological DMARDs directed against the inflammatory mediator TNF-a (infliximab, adalimumab, entanercept) are effective in only 60% of patients and in those with long standing disease, the response can be transient with approximately half of patients becoming refractory to treatment within 2 years.
There is clearly a need for an orally-available, well tolerated, inexpensive drug that could block the production of TNF associated with pathological inflammation found in RA and related conditions.
Invention:
Researchers based at a London-based university have identified an off-target effect of a marketed, small molecule anti-depressant, which inhibits TNF-a production by blocking TLR-8. The effects have been demonstrated in both in vitro human RA synovial and in vivo collagen induced models of RA. This work demonstrates that TLR-8 is a potential new target for RA and the research group are developing second generation, more potent analogues which retain the anti-inflammatory action but have no sedative effects.
Development Stage:
This project is currently in the lead-optimization phase and a pre-candidate likely within 12-18 months. A composition of matter patent has been filed and the group are now seeking a partner to further test, develop and market these compounds for the treatment for rheumatoid arthritis.
Innovative Aspects:
TNF-a inhibitor that is:
- orally available
- reduced side-effect profile
- inexpensive
Degree of development:
Patents/Rights: Patent(s) applied for but not yet granted
Requested Cooperation: License Agreement
- Type of partner sought: Pharmaceutical, drug discovery.
- Specific area of activity of the partner: pharmaceutical, drug discovery, drug developing and testing.
- Task to be performed by the partner sought: testing, developing and marketing.
Type of Organisation:
Status: NEW
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