Wow, M30 is a very interesting compound. the group in Haifa that developed it has had it
since 2005. Eight years seems like enough time to figure out if it's toxic and get it into humans. I wonder if that's happened yet?
Here's a recent report of an animal experiment:
Mech Ageing Dev. 2012 May;133(5):267-74. doi: 10.1016/j.mad.2012.03.001. Epub 2012 Mar 10.
Neuroprotection by the multitarget iron chelator M30 on age-related alterations in mice.
Kupershmidt L, Amit T, Bar-Am O, Youdim MB, Weinreb O.
Eve Topf Centers of Excellence for Neurodegenerative Diseases Research and Department of Pharmacology, Rappaport Family Research Institute Technion-Faculty of Medicine, Haifa 31096, Israel.
Based on a multimodal drug design paradigm, we have synthesized a multifunctional non-toxic, brain permeable iron chelating compound, M30, possessing the neuroprotective N-propargyl moiety of the anti-Parkinsonian drug, monoamine oxidase (MAO)-B inhibitor, rasagiline and the antioxidant-iron chelator moiety of an 8-hydroxyquinoline derivative of the iron chelator, VK28. Here, we report that a chronic systemic treatment of aged mice with M30 (1 and 5mg/kg; 4 times weekly for 6 months), had a significant positive impact on neuropsychiatry functions and cognitive age-related impairment. M30 significantly reduced cerebral iron accumulation as demonstrated by Perl's staining, accompanied by a marked decrease in cerebral β-amyloid plaques. In addition, our results demonstrate that M30 caused a significant inhibition of both MAO-A and -B activities in the cerebellum of aged mice, compared with vehicle-treated aged control mice. In summary, the present study indicates that the novel MAO inhibitor/iron chelating drug, M30, acting against multiple brain targets could reverse age-associated memory impairment and provide a potential treatment against the progression of neurodegeneration in ageing.
PMID: 22426424
The following might explain where things are going- the guys from the Haifa group have started (or hooked up with) a company in the US. I would guess they are going to try to take it far enough forward to sell it to a big pharma for very large money, or less likely, try to take it all the way to market themselves. Either way, expect it to take a hell of a long time to see the light of day. I imagine that intrepid experimenters could get a batch whipped up by a Chinese synthesis house without too much trouble.
Alzheimers Dis. 2012;30(1):1-16. doi: 10.3233/JAD-2012-120013.
From anti-Parkinson's drug rasagiline to novel multitarget iron chelators with acetylcholinesterase and monoamine oxidase inhibitory and neuroprotective properties for Alzheimer's disease.
Zheng H, Amit T, Bar-Am O, Fridkin M, Youdim MB, Mandel SA.
Department of Medicinal Chemistry, Intra-Cellular Therapies Inc., New York, NY, USA.
Alzheimer's disease (AD) is a multifactorial syndrome involving a complex array of different, while related, factors in its progression. Accordingly, novel approaches that can simultaneously modulate several disease-related targets hold great promise for the effective treatment of AD. This review describes the development of novel hybrid molecules with multimodal activity, including: i) M30, the brain permeable selective monoamine oxidase (MAO)-A and -B inhibitor with chelating and neuroprotective activity; ii) HLA20, a brain permeable metal chelator with neuroprotective activity; iii) HLA20A, an acetylcholinesterase (AChE) inhibitor with site-activated chelating and neuroprotective activity; iv) M30D, an AChE and MAO-A and -B inhibitor with site-activated chelating and neuroprotective activity; and v) analogs of the neuroprotective aminoacid peptide, NAPVSIPQ. HLA20A and M30D act as pro-chelators and can be activated to liberate their respective active chelators HLA20 and M30 through pseudo inhibition of AChE. We first discuss the knowledge and structure-based strategy for the rational design of these novel compounds. Then, we review our recent studies on these drug candidates, regarding their wide range in vitro and in vivo activities, with emphasis on antioxidant-chelating potency and AchE and MAO-A and -B inhibitory activity, as well as neuroprotective/neurorescue effects. Finally, we discuss the diverse molecular mechanisms of action of these compounds with relevance to AD, including modulation of amyloid-β; and amyloid-β; protein precursor expression/processing; induction of cell cycle arrest; inhibition of neuronal death markers; and upregulation of neurotrophic factors, as well as activation of protein kinase signaling pathways.
PMID: 22387411
