Rupintrivir
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MedKoo CAT#: 529307

CAS#: 223537-30-2

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

Chemical Structure

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Rupintrivir
CAS# 223537-30-2
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 529307
Name: Rupintrivir
CAS#: 223537-30-2
Chemical Formula: C31H39FN4O7
Exact Mass: 598.28
Molecular Weight: 598.670
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 350
10mg USD 650
25mg USD 1350
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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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.0 83.52
DMSO 50.0 83.52

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.

Recalculate based on batch purity %
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: 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.
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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1: 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. PubMed PMID: 24890597; PubMed Central PMCID: PMC4136040.

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. PubMed PMID: 23295352.

3: Wu C, Cai Q, Chen C, Li N, Peng X, Cai Y, Yin K, Chen X, Wang X, Zhang R, Liu L, Chen S, Li J, Lin T. Structures of Enterovirus 71 3C proteinase (strain E2004104-TW-CDC) and its complex with rupintrivir. Acta Crystallogr D Biol Crystallogr. 2013 May;69(Pt 5):866-71. doi: 10.1107/S0907444913002862. PubMed PMID: 23633597.

4: Hung HC, Wang HC, Shih SR, Teng IF, Tseng CP, Hsu JT. Synergistic inhibition of enterovirus 71 replication by interferon and rupintrivir. J Infect Dis. 2011 Jun 15;203(12):1784-90. doi: 10.1093/infdis/jir174. PubMed PMID: 21536800.

5: Zhang XN, Song ZG, Jiang T, Shi BS, Hu YW, Yuan ZH. Rupintrivir is a promising candidate for treating severe cases of Enterovirus-71 infection. World J Gastroenterol. 2010 Jan 14;16(2):201-9. PubMed PMID: 20066739; PubMed Central PMCID: PMC2806558.

6: Wang J, Fan T, Yao X, Wu Z, Guo L, Lei X, Wang J, Wang M, Jin Q, Cui S. Crystal structures of enterovirus 71 3C protease complexed with rupintrivir reveal the roles of catalytically important residues. J Virol. 2011 Oct;85(19):10021-30. doi: 10.1128/JVI.05107-11. PubMed PMID: 21813612; PubMed Central PMCID: PMC3196404.

7: Lacroix C, George S, Leyssen P, Hilgenfeld R, Neyts J. The enterovirus 3C protease inhibitor SG85 efficiently blocks rhinovirus replication and is not cross-resistant with rupintrivir. Antimicrob Agents Chemother. 2015 Sep;59(9):5814-8. doi: 10.1128/AAC.00534-15. PubMed PMID: 26055377; PubMed Central PMCID: PMC4538484.

8: Lu G, Qi J, Chen Z, Xu X, Gao F, Lin D, Qian W, Liu H, Jiang H, Yan J, Gao GF. Enterovirus 71 and coxsackievirus A16 3C proteases: binding to rupintrivir and their substrates and anti-hand, foot, and mouth disease virus drug design. J Virol. 2011 Oct;85(19):10319-31. doi: 10.1128/JVI.00787-11. PubMed PMID: 21795339; PubMed Central PMCID: PMC3196414.

9: Binford SL, Weady PT, Maldonado F, Brothers MA, Matthews DA, Patick AK. In vitro resistance study of rupintrivir, a novel inhibitor of human rhinovirus 3C protease. Antimicrob Agents Chemother. 2007 Dec;51(12):4366-73. PubMed PMID: 17908951; PubMed Central PMCID: PMC2167992.

10: Binford SL, Maldonado F, Brothers MA, Weady PT, Zalman LS, Meador JW 3rd, Matthews DA, Patick AK. Conservation of amino acids in human rhinovirus 3C protease correlates with broad-spectrum antiviral activity of rupintrivir, a novel human rhinovirus 3C protease inhibitor. Antimicrob Agents Chemother. 2005 Feb;49(2):619-26. PubMed PMID: 15673742; PubMed Central PMCID: PMC547258.

11: Burns-Naas LA, Lee C, Evering W, Ahern L, Webber S, Zorbas M. Lack of respiratory and contact sensitizing potential of the intranasal antiviral drug candidate rupintrivir (AG7088): a weight-of-the-evidence evaluation. J Immunotoxicol. 2005 Jul 1;2(3):123-39. doi: 10.1080/15476910500203925. PubMed PMID: 18958666.

12: Ang MJ, Lau QY, Ng FM, Then SW, Poulsen A, Cheong YK, Ngoh ZX, Tan YW, Peng J, Keller TH, Hill J, Chu JJ, Chia CS. Peptidomimetic ethyl propenoate covalent inhibitors of the enterovirus 71 3C protease: a P2-P4 study. J Enzyme Inhib Med Chem. 2016;31(2):332-9. doi: 10.3109/14756366.2015.1018245. PubMed PMID: 25792507.

13: Wang Y, Li G, Yuan S, Gao Q, Lan K, Altmeyer R, Zou G. In Vitro Assessment of Combinations of Enterovirus Inhibitors against Enterovirus 71. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5357-67. doi: 10.1128/AAC.01073-16. PubMed PMID: 27353263; PubMed Central PMCID: PMC4997834.

14: Costenaro L, Kaczmarska Z, Arnan C, Janowski R, Coutard B, Solà M, Gorbalenya AE, Norder H, Canard B, Coll M. Structural basis for antiviral inhibition of the main protease, 3C, from human enterovirus 93. J Virol. 2011 Oct;85(20):10764-73. doi: 10.1128/JVI.05062-11. PubMed PMID: 21835784; PubMed Central PMCID: PMC3187475.

15: Jetsadawisut W, Nutho B, Meeprasert A, Rungrotmongkol T, Kungwan N, Wolschann P, Hannongbua S. Susceptibility of inhibitors against 3C protease of coxsackievirus A16 and enterovirus A71 causing hand, foot and mouth disease: A molecular dynamics study. Biophys Chem. 2016 Dec;219:9-16. doi: 10.1016/j.bpc.2016.09.005. PubMed PMID: 27668727.

16: Tijsma A, Franco D, Tucker S, Hilgenfeld R, Froeyen M, Leyssen P, Neyts J. The capsid binder Vapendavir and the novel protease inhibitor SG85 inhibit enterovirus 71 replication. Antimicrob Agents Chemother. 2014 Nov;58(11):6990-2. doi: 10.1128/AAC.03328-14. PubMed PMID: 25199773; PubMed Central PMCID: PMC4249361.

17: Smee DF, Evans WJ, Nicolaou KC, Tarbet EB, Day CW. Susceptibilities of enterovirus D68, enterovirus 71, and rhinovirus 87 strains to various antiviral compounds. Antiviral Res. 2016 Jul;131:61-5. doi: 10.1016/j.antiviral.2016.04.003. PubMed PMID: 27063860; PubMed Central PMCID: PMC5100981.

18: Shang L, Wang Y, Qing J, Shu B, Cao L, Lou Z, Gong P, Sun Y, Yin Z. An adenosine nucleoside analogue NITD008 inhibits EV71 proliferation. Antiviral Res. 2014 Dec;112:47-58. doi: 10.1016/j.antiviral.2014.10.009. PubMed PMID: 25446894.

19: Mello C, Aguayo E, Rodriguez M, Lee G, Jordan R, Cihlar T, Birkus G. Multiple classes of antiviral agents exhibit in vitro activity against human rhinovirus type C. Antimicrob Agents Chemother. 2014;58(3):1546-55. doi: 10.1128/AAC.01746-13. PubMed PMID: 24366736; PubMed Central PMCID: PMC3957863.

20: Kawatkar SP, Gagnon M, Hoesch V, Tiong-Yip C, Johnson K, Ek M, Nilsson E, Lister T, Olsson L, Patel J, Yu Q. Design and structure-activity relationships of novel inhibitors of human rhinovirus 3C protease. Bioorg Med Chem Lett. 2016 Jul 15;26(14):3248-52. doi: 10.1016/j.bmcl.2016.05.066. PubMed PMID: 27265257.