Synucleozid

Synucleozid (NSC 377363) is a potent inhibitor of the SNCA mRNA that encodes α-synuclein protein (IC50=1.5 μM). Synucleozid selectively targets the α-synuclein mRNA 5′ UTR at the designed IRE site, decreases the amount of SNCA mRNA loaded into polysomes and thereby inhibits SNCA translation. Synucleozid has the potential for the investigation of Parkinson’s disease.

Product information

CAS Number: 502139-01-7

Molecular Weight: 368.43

Formula: C22H20N6

Synonym:

NSC 377363

Chemical Name: 2-{4-[(4-carbamimidoylphenyl)amino]phenyl}-1H-indole-6-carboximidamide

Smiles: NC(=N)C1=CC2NC(=CC=2C=C1)C1C=CC(=CC=1)NC1C=CC(=CC=1)C(N)=N

InChiKey: TZRXNWCLKYWDNH-UHFFFAOYSA-N

InChi: InChI=1S/C22H20N6/c23-21(24)14-5-9-18(10-6-14)27-17-7-3-13(4-8-17)19-11-15-1-2-16(22(25)26)12-20(15)28-19/h1-12,27-28H,(H3,23,24)(H3,25,26)

Technical Data

Appearance: Solid Power

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

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:

Synucleozid (0.25-1 μM; 24 hours) abrogates cytotoxicity induced by α-synuclein preformed fibrils, which act as seeds and recruit endogenous α-synuclein to aggregate. Synucleozid (0-1 μM; 24 hours) binds to the A bulge near the base of the IRE hairpin, reduced levels of α-synuclein in a dose-dependent manner with an IC50 of 500 nM, and inhibits α-synuclein protein expression in SH-SY5Y neuroblastoma cells. Synucleozid (100 nM-100 μM; 24 hours) binds to 2-AP-labeled and native IRE RNA with similar affinities. It decreases 2-AP emission with an EC50 value of 2.7 μM, recovery of 2-AP emissions is observed as a function of unlabeled SNCA IRE RNA (RNA-0) concentration, affording a competitive Kd of 1.5 μM. Synucleozid (0.25-1 μM; 24 hours) decreases α-synuclein and other proteins that have IREs in their mRNA’s UTR including APP, PrP, Ferritin and TfR as a dose-dependent mannner. All panels is completed in SH-SY5Y cells, except for PrP protein which is assessed in Neuro-2A cells.

References:

1. Zhang P, et al. Translation of the intrinsically disordered protein α-synuclein is inhibited by a small molecule targeting its structured mRNA.Proc Natl Acad Sci U S A. 2020 Jan 21;117(3):1457-1467.

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