Rupintrivir | CAS#223537-30-2 | rhinovirus 3C protease inhibitor

MedKoo Cat#: 529307 | Name: Rupintrivir

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Description:

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

Rupintrivir, also known as AG7088, is a rhinovirus 3C protease inhibitor potentially for the treatment of HRV infection.

Chemical Structure

Rupintrivir

CAS#223537-30-2

Theoretical Analysis

MedKoo Cat#: 529307

Name: Rupintrivir

CAS#: 223537-30-2

Chemical Formula: C31H39FN4O7

Exact Mass: 598.2803

Molecular Weight: 598.67

Elemental Analysis: C, 62.19; H, 6.57; F, 3.17; N, 9.36; O, 18.71

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 450.00	2 Weeks

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Related CAS #

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Synonym

AG-7088; AG7088; AG 7088; Rupintrivir

IUPAC/Chemical Name

ethyl (S,E)-4-((2R,5S)-2-(4-fluorobenzyl)-6-methyl-5-(5-methylisoxazole-3-carboxamido)-4-oxoheptanamido)-5-((S)-2-oxopyrrolidin-3-yl)pent-2-enoate

InChi Key

CAYJBRBGZBCZKO-BHGBQCOSSA-N

InChi Code

InChI=1S/C31H39FN4O7/c1-5-42-27(38)11-10-24(16-21-12-13-33-29(21)39)34-30(40)22(15-20-6-8-23(32)9-7-20)17-26(37)28(18(2)3)35-31(41)25-14-19(4)43-36-25/h6-11,14,18,21-22,24,28H,5,12-13,15-17H2,1-4H3,(H,33,39)(H,34,40)(H,35,41)/b11-10+/t21-,22+,24+,28-/m0/s1

SMILES Code

O=C(OCC)/C=C/[C@@H](NC([C@H](CC1=CC=C(F)C=C1)CC([C@@H](NC(C2=NOC(C)=C2)=O)C(C)C)=O)=O)C[C@H]3C(NCC3)=O

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

>2 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

Certificate of Analysis

View CoA: current batch, Lot#T20O04R23

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Rupatadine fumarate is a potent, orally active and long-lasting dual PAF/H1 antagonist, with Kis of 0.55 μM and 0.1 μM, respectively.

In vitro activity:

The in vitro activity of rupintrivir was explored in the context of human norovirus (HuNoV) replication. Rupintrivir inhibited the replication of the Norwalk virus replicon by targeting the norovirus protease. Sequence analysis revealed specific amino acid substitutions (A105V and I109V) in the viral protease NS6, contributing to enhanced resistance to rupintrivir. Reverse genetics in murine norovirus (MNV) validated that a single I109V substitution in the protease led to reduced susceptibility to rupintrivir. Reference: Antimicrob Agents Chemother. 2018 Apr 26;62(5):e00201-18. https://pubmed.ncbi.nlm.nih.gov/29530860/

In vivo activity:

Lung slices from HDM-sensitized asthmatic mice were infected ex vivo with human rhinovirus (RV), and the effects of rupintrivir on RV-induced cytokine responses were assessed. Rupintrivir treatment mitigated the exaggerated pro-inflammatory cytokine IL-6 and TH-2 cytokine IL-4 in HDM-sensitized mice, highlighting its potential in modulating immune responses in this context. Reference: Respir Res. 2019 Oct 22;20(1):228. https://pubmed.ncbi.nlm.nih.gov/31640701/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.0	83.52
	DMSO	50.0	83.52

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 598.67 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. Kitano M, Hosmillo M, Emmott E, Lu J, Goodfellow I. Selection and Characterization of Rupintrivir-Resistant Norwalk Virus Replicon Cells In Vitro. Antimicrob Agents Chemother. 2018 Apr 26;62(5):e00201-18. doi: 10.1128/AAC.00201-18. PMID: 29530860; PMCID: PMC5923142. 2. Rocha-Pereira J, Nascimento MS, Ma Q, Hilgenfeld R, Neyts J, Jochmans D. The enterovirus protease inhibitor rupintrivir exerts cross-genotypic anti-norovirus activity and clears cells from the norovirus replicon. Antimicrob Agents Chemother. 2014 Aug;58(8):4675-81. doi: 10.1128/AAC.02546-13. Epub 2014 Jun 2. PMID: 24890597; PMCID: PMC4136040. 3. Danov O, Lasswitz L, Obernolte H, Hesse C, Braun A, Wronski S, Sewald K. Rupintrivir reduces RV-induced TH-2 cytokine IL-4 in precision-cut lung slices (PCLS) of HDM-sensitized mice ex vivo. Respir Res. 2019 Oct 22;20(1):228. doi: 10.1186/s12931-019-1175-y. PMID: 31640701; PMCID: PMC6805592. 4. Zhang X, Song Z, Qin B, Zhang X, Chen L, Hu Y, Yuan Z. Rupintrivir is a promising candidate for treating severe cases of enterovirus-71 infection: evaluation of antiviral efficacy in a murine infection model. Antiviral Res. 2013 Mar;97(3):264-9. doi: 10.1016/j.antiviral.2012.12.029. Epub 2013 Jan 5. PMID: 23295352.

In vitro protocol:

In vivo protocol:

1. Danov O, Lasswitz L, Obernolte H, Hesse C, Braun A, Wronski S, Sewald K. Rupintrivir reduces RV-induced TH-2 cytokine IL-4 in precision-cut lung slices (PCLS) of HDM-sensitized mice ex vivo. Respir Res. 2019 Oct 22;20(1):228. doi: 10.1186/s12931-019-1175-y. PMID: 31640701; PMCID: PMC6805592. 2. Zhang X, Song Z, Qin B, Zhang X, Chen L, Hu Y, Yuan Z. Rupintrivir is a promising candidate for treating severe cases of enterovirus-71 infection: evaluation of antiviral efficacy in a murine infection model. Antiviral Res. 2013 Mar;97(3):264-9. doi: 10.1016/j.antiviral.2012.12.029. Epub 2013 Jan 5. PMID: 23295352.

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J Mol Graph Model. 2023 Jan;118:108345. doi: 10.1016/j.jmgm.2022.108345. Epub 2022 Oct 6. PMID: 36308946. 10: Le TTV, Do PC. Molecular docking study of various Enterovirus-A71 3C protease proteins and their potential inhibitors. Front Microbiol. 2022 Sep 29;13:987801. doi: 10.3389/fmicb.2022.987801. PMID: 36246267; PMCID: PMC9563145. 11: Ianevski A, Zusinaite E, Tenson T, Oksenych V, Wang W, Afset JE, Bjørås M, Kainov DE. Novel Synergistic Anti-Enteroviral Drug Combinations. Viruses. 2022 Aug 25;14(9):1866. doi: 10.3390/v14091866. PMID: 36146673; PMCID: PMC9505890. 12: Yuan X, Kadowaki T. DWV 3C Protease Uncovers the Diverse Catalytic Triad in Insect RNA Viruses. Microbiol Spectr. 2022 Jun 29;10(3):e0006822. doi: 10.1128/spectrum.00068-22. Epub 2022 May 16. PMID: 35575593; PMCID: PMC9241925. 13: Zhou X, Tian L, Wang J, Zheng B, Zhang W. EV71 3C protease cleaves host anti-viral factor OAS3 and enhances virus replication. Virol Sin. 2022 Jun;37(3):418-426. doi: 10.1016/j.virs.2022.04.013. Epub 2022 May 3. PMID: 35504537; PMCID: PMC9243667. 14: Sripattaraphan A, Sanachai K, Chavasiri W, Boonyasuppayakorn S, Maitarad P, Rungrotmongkol T. Computational Screening of Newly Designed Compounds against Coxsackievirus A16 and Enterovirus A71. Molecules. 2022 Mar 15;27(6):1908. doi: 10.3390/molecules27061908. PMID: 35335272; PMCID: PMC8955072. 15: Croft SN, Walker EJ, Ghildyal R. RIPK1 Is Cleaved by 3C Protease of Rhinovirus A and B Strains and Minor and Major Groups. Viruses. 2021 Nov 30;13(12):2402. doi: 10.3390/v13122402. PMID: 34960671; PMCID: PMC8703350. 16: Van Dycke J, Dai W, Stylianidou Z, Li J, Cuvry A, Roux E, Li B, Rymenants J, Bervoets L, de Witte P, Liu H, Neyts J, Rocha-Pereira J. A Novel Class of Norovirus Inhibitors Targeting the Viral Protease with Potent Antiviral Activity In Vitro and In Vivo. Viruses. 2021 Sep 16;13(9):1852. doi: 10.3390/v13091852. PMID: 34578432; PMCID: PMC8472913. 17: Lanko K, Shi C, Patil S, Delang L, Matthijnssens J, Mirabelli C, Neyts J. Assessing In Vitro Resistance Development in Enterovirus A71 in the Context of Combination Antiviral Treatment. ACS Infect Dis. 2021 Oct 8;7(10):2801-2806. doi: 10.1021/acsinfecdis.0c00872. Epub 2021 Sep 16. PMID: 34529400. 18: Lockbaum GJ, Henes M, Lee JM, Timm J, Nalivaika EA, Thompson PR, Kurt Yilmaz N, Schiffer CA. Pan-3C Protease Inhibitor Rupintrivir Binds SARS-CoV-2 Main Protease in a Unique Binding Mode. Biochemistry. 2021 Oct 5;60(39):2925-2931. doi: 10.1021/acs.biochem.1c00414. Epub 2021 Sep 10. PMID: 34506130; PMCID: PMC8457326. 19: Wronski S, Beinke S, Obernolte H, Belyaev NN, Saunders KA, Lennon MG, Schaudien D, Braubach P, Jonigk D, Warnecke G, Zardo P, Fieguth HG, Wilkens L, Braun A, Hessel EM, Sewald K. Rhinovirus-induced Human Lung Tissue Responses Mimic Chronic Obstructive Pulmonary Disease and Asthma Gene Signatures. Am J Respir Cell Mol Biol. 2021 Nov;65(5):544-554. doi: 10.1165/rcmb.2020-0337OC. PMID: 34181859; PMCID: PMC8641849. 20: Mousavi Maleki MS, Rostamian M, Madanchi H. Antimicrobial peptides and other peptide-like therapeutics as promising candidates to combat SARS-CoV-2. Expert Rev Anti Infect Ther. 2021 Oct;19(10):1205-1217. doi: 10.1080/14787210.2021.1912593. Epub 2021 Apr 12. PMID: 33844613; PMCID: PMC8054488.