NAB2, Rsp5/Nedd4 pathway activator, rescuing α-synuclein toxicity

Overview
Catalog #	bs-60153c-2mg-solid
Product Name	NAB2, Rsp5/Nedd4 pathway activator, rescuing α-synuclein toxicity
Specifications
Storage Buffer	Powder
Storage Condition	Store in dry, dark place at -20C for 1 year.
Target
Product Information	Molecular Weight: 389.88 Formula: C23 H20 Cl N3 O CAS Number: 1504588-00-4 InChi Key: CZSLEMCYYGEGKP-UHFFFAOYSA-N InChi: InChI=1S/C23H20ClN3O/c1-15-7-8-16(2)22(11-15)27-14-26-20-12-17(9-10-21(20)27)23(28)25-13-18-5-3-4-6-19(18)24/h3-12,14H,13H2,1-2H3,(H,25,28) Smiles: CC1C=CC(C)=CC=1N1C=NC2=CC(=CC=C12)C(=O)NCC1=CC=CC=C1Cl Purity: 98.0 Solubility: DMSO up to 50 mM Appearance: Solid Power. Shelf Life: 1.0 years
Description	NAB2 is a novel and highly potent small molecule that was shown to strongly and selectively protect diverse cell types from α-synuclein toxicity. NAB2 was identified by an unbiased phenotypic screening. Three chemical genetic screens in wild-type yeast cells established that NAB2 promoted endosomal transport events dependent on the E3 ubiquitin ligase Rsp5/Nedd4. These same steps were perturbed by α-synuclein itself. NAB2 reduced protein nitration in the yeast synucleinopathy model and decreased NO levels in A53T patient neurons. Moreover, NAB2 reduced the accumulation of immature ER forms of CPY in yeast. It increased the post-ER forms, and decreased the immature forms, of Nicastrin and GCase in PD patient neurons. NAB2 could be a useful chemical probe to study a druggable node in the biology of α-synuclein that can correct multiple aspects of its underlying pathology, including dysfunctional endosomal and endoplasmic reticulum-to-Golgi vesicle trafficking.