Mitochondrial dysfunction target discovery in lymphangioleiomyomatosis
exploratoryresearch program · medium
Identify therapeutic strategies for lymphangioleiomyomatosis by targeting mitochondrial biogenesis and mitochondrial dysfunction in LAM cells.
Array-based and metabolic molecular analysis of patient-derived LAM cell lines.
2019 publication identified mitochondrial biogenesis and dysfunction as a potential treatment target in LAM cells.
The study concluded that mitochondrial dysfunction is a key determinant of LAM and provides a novel therapeutic target for this orphan disease.
Novel flavonoids for breast cancer research program
exploratoryresearch program · medium
Evaluate flavonoids and improved novel flavonoid derivatives as potential breast cancer therapeutics.
Review and mechanistic synthesis of flavonoid anticancer mechanisms including antioxidant effects, phyto-oestrogen activity, CYP1 and ABC protein modulation, apoptosis induction, cell-cycle arrest, and signalling-pathway regulation.
2014 review summarized mechanisms and rationale for developing novel flavonoids with improved properties for breast cancer.
The review concluded that flavonoids have multiple anticancer mechanisms and that novel flavonoids with improved pharmacological properties held promise for breast cancer applications.
Novel flavonoid therapeutic antioxidant platform
exploratoryplatform · medium
Create flavonoid compounds with improved therapeutic antioxidant properties and better applicability in vivo.
Synthetic flavonoid chemistry focused on antioxidant compounds with modified properties, including improved lipid solubility relative to natural flavonoids.
European patent EP1534698B1 was granted in 2007 and is listed as expired in the supplied patent record.
The patent record describes flavonoid compounds as therapeutic antioxidants and notes that natural flavonoids have limited in vivo antioxidant application due to limited lipid solubility.
Oncamex breast cancer program
preclinicaldrug program · high
Develop a mitochondria-targeted redox-modulating flavonoid as an anticancer agent, with evidence in breast cancer models.
Second-generation myricetin-derived flavonoid analogue tested across breast cancer cell lines and in an MDA-MB-231 breast cancer xenograft mouse model.
2016 publication reported antiproliferative and antitumour activity in preclinical breast cancer models.
Oncamex reduced cell viability, induced cytotoxicity and apoptosis, altered cell-cycle and apoptosis gene expression, targeted mitochondria, modulated reactive oxygen species, and inhibited tumour growth in a preliminary mouse xenograft study without reported untoward effects.
Proxison neuroprotective antioxidant program
preclinicaldrug program · high
Protect neural cells from acute oxidative stress and potential oxidative-stress-related neurodegeneration.
Synthetic cell-permeable flavonoid antioxidant with a lipophilic hydrocarbon tail and modified polyphenolic head group; tested in vitro and in a zebrafish dopaminergic neurodegeneration model.
2017 publication reported in vitro rescue of oxidative-stress-damaged neural cells and in vivo neuroprotection in zebrafish.
Proxison showed radical scavenging activity, strong cellular protection against oxidative stress, moderate mitochondrial enrichment, and well tolerated neuroprotection against dopaminergic cell loss in zebrafish.
