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Chemical Structure| 2817811-10-0 Chemical Structure| 2817811-10-0

Structure of XR8-69
CAS No.: 2817811-10-0

Chemical Structure| 2817811-10-0

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Shen, Zhengnan ; Ratia, Kiira ; Cooper, Laura ; Kong, Deyu ; Lee, Hyun ; Kwon, Youngjin , et al.

Abstract: Antiviral agents that complement vaccination are urgently needed to end the COVID-19 pandemic. The SARS-CoV-2 papain-like protease (PLpro), one of only two essential cysteine proteases that regulate viral replication, also dysregulates host immune sensing by binding and deubiquitination of host protein substrates. PLpro is a promising therapeutic target, albeit challenging owing to featureless P1 and P2 sites recognizing glycine. To overcome this challenge, we leveraged the cooperativity of multiple shallow binding sites on the PLpro surface yielding novel 2-phenylthiophenes with nanomolar inhibitory potency. New co-crystal structures confirmed that ligand binding induces new interactions with PLpro: by closing of the BL2 loop of PLpro forming a novel “BL2 groove”; and by mimicking the binding interaction of ubiquitin with Glu167 of PLpro. Together, this binding cooperativity translates to the most potent PLpro inhibitors reported to date, with slow off-rates, improved binding affinities, and low micromolar antiviral potency in SARS-CoV-2-infected human cells.

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Product Details of XR8-69

CAS No. :2817811-10-0
Formula : C26H30N4O2S
M.W : 462.61
SMILES Code : O=C(N[C@@H](C1=CC=CC(C2=CC=C(CNC(C)=O)S2)=C1)C)C3=CC(NC4CNC4)=CC=C3C
MDL No. :N/A

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Isoform Comparison

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.16mL

0.43mL

0.22mL

10.81mL

2.16mL

1.08mL

21.62mL

4.32mL

2.16mL

 

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