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

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.

Product information

CAS Number: 1504588-00-4

Molecular Weight: 389.88

Formula: C23H20ClN3O

Synonym:

alphaSYN-IN-NAB2

alphaSYN inhibitor NAB2

α-Synuclein inhibitor NAB2

Rsp5/Nedd4 actovator NAB2

Chemical Name: 2-(4-benzoylphenoxy)-N-(1-benzylpiperidin-4-yl)acetamide

Smiles: CC1C=C(C(C)=CC=1)N1C=NC2=CC(=CC=C12)C(=O)NCC1=CC=CC=C1Cl

InChiKey: 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)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 50 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

NAB2 was used at 2.5-5 µM final concentration in vitro and in cellular assays.

In Vivo:

n/a

References:

1. Tardiff DF, et al. Yeast reveal a "druggable" Rsp5/Nedd4 network that ameliorates α-synuclein toxicity in neurons. (2013) Science. 342(6161):979-83.
2. Chung CY, et al. Identification and rescue of α-synuclein toxicity in Parkinson patient-derived neurons. (2013) Science. 342(6161):983-7.

Products are for research use only. Not for human use.

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