Three new Neuroscience small molecules – only at REAGENCY
AUTEN-67 MTMR14 inhibitor (RGNCY-0046)
AUTEN-67 is a specific inhibitor of MTMR14, a myotubularin-related phosphatase antagonizing the formation of autophagic membrane structures. It significantly increases autophagic flux in cell lines and in vivo models. AUTEN-67 promotes longevity and protects neurons from undergoing stress-induced cell death. It also restores nesting behavior in a murine model of Alzheimer disease,without apparent side effects. Therefore, AUTEN-67 can be used as a potent drug candidate to decelerate the aging process and counter various age-dependent degenerative diseases.
LDDN-0003499 Src inhibitor (RGNCY-0045)
LDDN-0003499 is a novel small molecule Src family tyrosine kinase inhibitor with anti-inflammatory effects in response to Aβ stimulation of microglia. It produced a dose dependent decrease in basal levels of active, phosphorylated Src and Lyn in BV2 cells (microglial cell line). LDDN-0003499 treatment also attenuated the Aβ-stimulated increase in active, phosphorylated levels of Lyn/Src and TNFα and IL-6 secretion. This compound also has properties that suggest oral availability and blood brain barrier penetration. Furthermore, in vitro/in vivo characterization of LDDN-0003499 as well as structural modification may provide a new tool for attenuating microglial-mediated brain inflammatory conditions such as that occurring in AD.
TBTC RXR alpha agonist (RGNCY-0044)
TBTC, a thiophene derivative, is a selective agonist of retinoid X receptor α (RXRα). It can effectively activate the heterodimerization of RXRα, with either liver X receptor α (LXRα) or peroxisome proliferator activated receptor γ (PPARγ), stimulate the expressions of the genes of apoE, ABCA1and ABCG1, and decrease Aβ content both in cells and animal models. In addition, administration of TBTC (30mg/kg/day) in the transgenic APP–PS1 mice could also reduce the formation of senile plaques and improve the daily living activity of the mice. Thus, TBTC may be a potential drug lead compound for the treatment of AD. RXRαLBD KD = 8.86 μM.
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