12 Aug The assignment is to summarize the preclinical information that has been collected on the candidate molecule
General Instructions
The assignment is to summarize the preclinical information that has been collected on the candidate molecule, determine which therapeutic indication that you think is most appropriate for this compound, evaluate its competitive viability, estimate its commercial potential, identify major concerns or limitations to the molecule and suggest potential remedies and make a team recommendation regarding advancement to clinical trials.
For the purpose of this exercise, teams can assume that the pharmacological (i.e not pharmacokinetic) properties of ERB-525 are essentially the same as other selective ER-b agonist molecules in the references below. Each team will determine which therapeutic indication to recommend and you are encouraged to review the literature to obtain additional information to support the scientific and commercial rationale for your recommendation.
The references on Blackboard represent some of the earlier target validation but considerably more work has been done on this mechanism. There are a few other potential therapeutic indications that have been identified for this class of drug and some of them are quite compelling. Do your research!
Indication- Antidepressant =data relevant to therapeutic indication
Target: Hypothalamus
THE GOAL IS TO FIND RESEARCH ON THE INDICATION AND TARGET USING COMPETEION COMMERICAL POTENTIAL AND RECCOMENDATION
1.Competition
2. Commercial Potential
3. Recommendation
Presentation Materials
ERB-525 Technical Report – 22 pages Literature References
Harris, HA. Estrogen Receptor-b: Recent lessons from in vivo studies. Mol. Endocrinol. 21:1-13, 2007
Pain and Inflammation
Leventhal, L. et al., An estrogen receptor-b agonist is active in models of inflammatory and chemical- induced pain. Eur. J. of Pharmacol. 553:146-148, 2006.
Harris, HA. et al., Evaluation of an estrogen receptor-b agonist in animal models of human disease. Endocrinol. 144:4241-4249, 2003.
Malamas, MS. et al., Design and synthesis of aryl diphenolic azoles as potent and selective estrogen receptor-b ligands. J. Med. Chem. 47:5021-5040, 2004
Mood Disorders
Clark, JA. et al., Selective estrogen receptor-beta (SERM-beta) compounds modulate raphe nuclei tryptophan hydroxylase-1 (TPH-1) mRNA expression and cause antidepressant-like effects in the forced swim test. Neuropharmacol. 63:1051-1063, 2012.
Hughes, ZA., et al., WAY-200070, a selective agonist of estrogen receptor beta as a potential novel anxiolytic/antidepressant agent. Neurophamacol. 54:1136-1142, 2008.
Wilkening, RR. et al., The discovery of tetrahydrofluorenones as a new class of estrogen receptor b- subtype selective ligands. Bioorganic & Med. Chem. Lett. 16:3489-3494, 2006
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