Lead-like libraries from 3D-fragments
Cresset Discovery Services has provided in silico design expertise and robust cheminformatics capabilities to Liverpool ChiroChem (LCC) in order to ...
Profitable reprofiling opportunities are often created by the publication of new biological targets. When new targets are identified, Blaze can be used to make a rapid assessment of whether any existing drugs are likely to be active against the new target.
In traditional development cycles compounds are usually narrowly tested against one disease indication. This means that a compound may make it all the way to market for a particular medical need without ever having been tested for other indications, often for good economic and ethical reasons.
However, such marketed drugs do represent an excellent source of medications for other indications due to their having well-known safety profiles. Such changes of use are referred to as reprofiling or repurposing.
Recent months have seen a steady news flow about reprofiling successes. Examples include PsiOxus’ reprofiling of s-pindolol for treatment of cachexia in cancer patients and Noven Pharmaceuticals’ launch of reprofiled paroxetine for menopausal ‘hot flashes’. These results highlight the scientific, economic and health benefits of reprofiling.
Reprofiling typically will not lead to a substance of matter (SOM) patent, but it can lead to a new use patent for the existing compound. New use patents offer the same 20 years of patent protection, and due to shorter development paths, usually have a much longer marketable life than a typical substance of matter patent. The comparison is typically 15 years for a new use compared to perhaps only 7 years for an SOM patent. This means that there is an economic benefit as well as a medical benefit to finding new uses.
However, one issue with reprofiled compounds has always been the existence of the original compound, usually available as a generic product, licensed for the original indication. Now there is an increasing trend to litigation of off-label use of medicines and, particularly in the US, a reluctance for reimbursers (typically the large HMO’s and insurance companies) to pay for off-label use. These factors result in an increasingly attractive environment for reprofiled compounds.
Reprofiling opportunities are often created by the publication of new biological targets. When such new targets are identified it is advantageous to be able to rapidly assess whether any existing drugs may thus find an alternative use.
Computational reprofiling is a very efficient way of identifying these new opportunities. It proceeds by comparing existing drug molecules against compounds active against a particular disease in order to look for similarities that will indicate potential for activity against that new indication. Blaze from Cresset is an ideal means of doing this. Blaze utilizes 3D properties of molecules, not just 2D structures; and our innovation for 2013, BlazeGPU, makes it possible to do this faster than ever before, utilizing affordable computer hardware. In combination with strong clinical and pharmacological knowledge, BlazeGPU is an excellent means of finding the possibilities hidden among existing drug compounds.