Tumour Vascular Targeting Agents

A new pharmacophore for selective targeting of tumour blood-supply BACKGROUND Cancer is a huge killer, responsible for more than 500,000 deaths in the US and 150,000 in the UK each year, thus making new anti-cancer drugs a key driver in the pharmaceutical industry. Most cancer treatments are poorly targeted and inherently toxic to the patient. Anti-vascular drugs for cancer treatment offer a potential solution to these problems, since they specifically target the tumour vasculature which is non-malignant and less likely to become resistant to this type of therapy. The key advantage of anti-vascular drugs is their ability to induce the shutdown of bloodflow to a tumour both selectively and rapidly (e.g. within minutes), whilst leaving normal vasculature intact. Thus, they have potential as pharmaceuticals of inherently low toxicity, capable of slowing down or stopping the proliferation of solid tumours. THE TECHNOLOGY Tumour growth must be supported by a concomitant expansion of blood vessels but, unlike normal vessels, tumour vasculature is highly disorganised, vessels being tortuous and dilated, with uneven diameter, excessive branching and shunts. Agents which can selectively disrupt such vasculature should have an important role in cancer therapy. In this context, the natural product combretastatin A4 (CA4) has been shown to be capable of selectively destroying tumour vasculature. Scientists in Manchester and Salford have recently generated a novel series of heterocyclic compounds which have been screened for growth inhibitory activity (IC50) against the K562 human chronic myelogenous leukemia cell-line using the MTT assay, and for their ability to inhibit the assembly of tubulin, a key cellular protein. Tubulin is a primary screen for anti-vascular agents as all the agents which target tumour vasculature also target tubulin. These heterocycles have also shown the ability to shutdown bloodflow in in vivo models. At present these heterocycles are being optimised to produce the most effective analogue (increased bioactivity, increased solubility). TURNING INNOVATIVE KEY BENEFITS
• Act primarily on the rapidly proliferating tumour vasculature.
• Unlikely to give rise to resistance to direct acting anti-tumour drugs.
• Endothelial cells are exposed to the highest drug concentration.
• Rapid clearance of drug reduces the side effects.
• Potential to treat any type of solid tumours. APPLICATIONS
• Oncology – esp. solid tumours
• Macular degeneration
• Diabetic retinopathy
• Psoriasis
• Endometriosis INTELLECTUAL PROPERTY A UK preliminary patent has been filed. Further intellectual property is being developed. OPPORTUNITY The technology is currently at an early-stage with in vitro and initial in vivo data indicating that the pharmacophore interacts with tubulin and is able to damage tumour vasculature. We seek discussion, under confidentiality agreement, with a potential licensee/collaboration partner to assist in the development and commercialisation of this technology. CONTACT Richard Price Business Manager, UMIP, The Fairbairn Building, PO Box No 88 Manchester M60 1QD [email protected] Tel: 0161 306 8528

Type of Offer: Licensing



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