GRL0617 | CAS#1093070-16-6 | SARS PLPro inhibitor

MedKoo Cat#: 593151 | Name: GRL0617

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

GRL0617 is a potent, selective and competitive noncovalent inhibitor of SARS PLPro. GRL0617, inhibited SARS-CoV viral replication in Vero E6 cells with an EC(50) of 15 microM and had no associated cytotoxicity. The X-ray structure of PLpro in complex with GRL0617 indicates that the compound has a unique mode of inhibition whereby it binds within the S4-S3 subsites of the enzyme and induces a loop closure that shuts down catalysis at the active site.

Chemical Structure

GRL0617

CAS#1093070-16-6

Theoretical Analysis

MedKoo Cat#: 593151

Name: GRL0617

CAS#: 1093070-16-6

Chemical Formula: C20H20N2O

Exact Mass: 304.1576

Molecular Weight: 304.39

Elemental Analysis: C, 78.92; H, 6.62; N, 9.20; O, 5.26

Price and Availability

Size	Price	Availability	Quantity
25mg	USD 550.00	2 Weeks
100mg	USD 1,050.00	2 Weeks

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Related CAS #

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Synonym

GRL-0617; GRL 0617; GRL0617; (-)-GRL-0617;

IUPAC/Chemical Name

5-Amino-2-methyl-N-[(1R)-1-(1-naphthalenyl)ethyl]benzamide

InChi Key

UVERBUNNCOKGNZ-CQSZACIVSA-N

InChi Code

InChI=1S/C20H20N2O/c1-13-10-11-16(21)12-19(13)20(23)22-14(2)17-9-5-7-15-6-3-4-8-18(15)17/h3-12,14H,21H2,1-2H3,(H,22,23)/t14-/m1/s1

SMILES Code

O=C(N[C@@H](C1=C2C=CC=CC2=CC=C1)C)C3=CC(N)=CC=C3C

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

GRL0617 is a selective and competitive noncovalent inhibitor of severe acute respiratory syndrome (SARS-CoV) papain-like protease (PLpro), with an IC50 of 0.6 μM and a Ki value of 0.49 μM. GRL0617 also inhibits SARS-CoV with an EC50 of 14.5 μM.

In vitro activity:

Inhibitor GRL0617 showed a promising in vitro IC50 of 2.1 μM and an effective antiviral inhibition in cell-based assays. The co-crystal structure of SARS-CoV-2 PLproC111S in complex with GRL0617 indicates that GRL0617 is a non-covalent inhibitor and it resides in the ubiquitin-specific proteases (USP) domain of PLpro. Reference: Nat Commun. 2021 Jan 20;12(1):488. https://pubmed.ncbi.nlm.nih.gov/33473130/

In vivo activity:

TBD

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	98.56
	DMSO	62.6	205.69
	Ethanol	26.2	86.14

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 304.39 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Fu Z, Huang B, Tang J, Liu S, Liu M, Ye Y, Liu Z, Xiong Y, Zhu W, Cao D, Li J, Niu X, Zhou H, Zhao YJ, Zhang G, Huang H. The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery. Nat Commun. 2021 Jan 20;12(1):488. doi: 10.1038/s41467-020-20718-8. PMID: 33473130; PMCID: PMC7817691. 2. Ratia K, Pegan S, Takayama J, Sleeman K, Coughlin M, Baliji S, Chaudhuri R, Fu W, Prabhakar BS, Johnson ME, Baker SC, Ghosh AK, Mesecar AD. A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication. Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16119-24. doi: 10.1073/pnas.0805240105. Epub 2008 Oct 13. PMID: 18852458; PMCID: PMC2571001.

In vitro protocol:

In vivo protocol:

TBD

1: Shen Z, Ratia K, Cooper L, Kong D, Lee H, Kwon Y, Li Y, Alqarni S, Huang F, Dubrovskyi O, Rong L, Thatcher GR, Xiong R. Potent, Novel SARS-CoV-2 PLpro Inhibitors Block Viral Replication in Monkey and Human Cell Cultures. bioRxiv [Preprint]. 2021 Feb 15:2021.02.13.431008. doi: 10.1101/2021.02.13.431008. PMID: 33594371; PMCID: PMC7885923. 2: Pitsillou E, Liang J, Ververis K, Hung A, Karagiannis TC. Interaction of small molecules with the SARS-CoV-2 papain-like protease: In silico studies and in vitro validation of protease activity inhibition using an enzymatic inhibition assay. J Mol Graph Model. 2021 Jan 26;104:107851. doi: 10.1016/j.jmgm.2021.107851. Epub ahead of print. PMID: 33556646; PMCID: PMC7837617. 3: Pitsillou E, Liang J, Ververis K, Lim KW, Hung A, Karagiannis TC. Identification of Small Molecule Inhibitors of the Deubiquitinating Activity of the SARS-CoV-2 Papain-Like Protease: in silico Molecular Docking Studies and in vitro Enzymatic Activity Assay. Front Chem. 2020 Dec 8;8:623971. doi: 10.3389/fchem.2020.623971. PMID: 33364229; PMCID: PMC7753156. 4: Fu Z, Huang B, Tang J, Liu S, Liu M, Ye Y, Liu Z, Xiong Y, Zhu W, Cao D, Li J, Niu X, Zhou H, Zhao YJ, Zhang G, Huang H. The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery. Nat Commun. 2021 Jan 20;12(1):488. doi: 10.1038/s41467-020-20718-8. PMID: 33473130; PMCID: PMC7817691. 5: Jamalan M, Barzegari E, Gholami-Borujeni F. Structure-Based Screening to Discover New Inhibitors for Papain-like Proteinase of SARS-CoV-2: An In Silico Study. J Proteome Res. 2021 Jan 1;20(1):1015-1026. doi: 10.1021/acs.jproteome.0c00836. Epub 2020 Dec 22. PMID: 33350309; PMCID: PMC7770893. 6: Gao X, Qin B, Chen P, Zhu K, Hou P, Wojdyla JA, Wang M, Cui S. Crystal structure of SARS-CoV-2 papain-like protease. Acta Pharm Sin B. 2021 Jan;11(1):237-245. doi: 10.1016/j.apsb.2020.08.014. Epub 2020 Sep 2. PMID: 32895623; PMCID: PMC7467110. 7: Shin D, Mukherjee R, Grewe D, Bojkova D, Baek K, Bhattacharya A, Schulz L, Widera M, Mehdipour AR, Tascher G, Geurink PP, Wilhelm A, van der Heden van Noort GJ, Ovaa H, Müller S, Knobeloch KP, Rajalingam K, Schulman BA, Cinatl J, Hummer G, Ciesek S, Dikic I. Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity. Nature. 2020 Nov;587(7835):657-662. doi: 10.1038/s41586-020-2601-5. Epub 2020 Jul 29. PMID: 32726803; PMCID: PMC7116779. 8: Chaudhuri R, Tang S, Zhao G, Lu H, Case DA, Johnson ME. Comparison of SARS and NL63 papain-like protease binding sites and binding site dynamics: inhibitor design implications. J Mol Biol. 2011 Nov 25;414(2):272-88. doi: 10.1016/j.jmb.2011.09.030. Epub 2011 Sep 29. PMID: 22004941; PMCID: PMC3397151. 9: Ratia K, Pegan S, Takayama J, Sleeman K, Coughlin M, Baliji S, Chaudhuri R, Fu W, Prabhakar BS, Johnson ME, Baker SC, Ghosh AK, Mesecar AD. A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication. Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16119-24. doi: 10.1073/pnas.0805240105. Epub 2008 Oct 13. PMID: 18852458; PMCID: PMC2571001.