176655-56-4

Basic information

• Product Name: Hydroxy Ritonavir
• Synonyms: Hydroxy Ritonavir;[5S-(5R*,8R*,10R*,11R*)]-10-Hydroxy-1-[2-(1-hydroxy-1-Methylethyl)-4-thiazolyl]-2-Methyl-5-(1-Methylethyl)-3,6-dioxo-8,11-bis(phenylMethyl)-;Ritonavir IMpurity E (Hydroxy Ritonavir)
• CAS NO: 176655-56-4
• Molecular Formula: C37H48N6O6S2
• Molecular Weight: 736.94362
• Product Categories: Chiral Reagents;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Sulfur & Selenium Compounds
• Mol File: 176655-56-4.mol

Chemical Properties

• Appearance: /
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Ethyl Acetate (Slightly)
• CAS DataBase Reference: Hydroxy Ritonavir(CAS DataBase Reference)
• NIST Chemistry Reference: Hydroxy Ritonavir(176655-56-4)
• EPA Substance Registry System: Hydroxy Ritonavir(176655-56-4)

Safety Data

• Hazardous Substances Data: 176655-56-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Hydroxy Ritonavir is used as an active pharmaceutical ingredient (API) for the treatment of HIV-1 infections. As a metabolite of Ritonavir, it contributes to the overall efficacy of the drug in inhibiting the replication of the virus, thus helping to manage the progression of the disease in patients.
Used in COVID-19 Research:
Hydroxy Ritonavir is used as a research compound in the context of COVID-19. Its potential applications in this area are being explored, as it may offer insights into the development of new treatments or therapies for the disease. The compound's role in HIV-1 protease inhibition makes it a promising candidate for further investigation into its possible effects on other viral infections, such as COVID-19.

Upstream product

• 155213-67-5 ritonavir 

Relevant articles and documents

Recombinant expression and characterization of novel P450s from Actinosynnema mirum

Cytochrome P450 monooxygenases (P450s) are the major contributor in the metabolism of xenobiotics, including therapeutic agents. Thus, P450s find broad application in the pharmaceutical industry to synthesize metabolites of new active pharmaceutical ingredients in order to evaluate toxicity and pharmacokinetics. As an alternative to human hepatic P450s, microbial P450s offer several advantages, such as an easier and more efficient heterologous expression as well as higher stability under process conditions. Recently, the wild-type strain Actinosynnema mirum has been reported to catalyze hydroxylation reactions with high activity on a broad range of substrates. In this study, one of these substrates, ritonavir, was used to analyze the transcriptional response of the wild-type strain. Analysis of the differential gene expression pattern allowed the assignment of genes potentially responsible for ritonavir conversion. Heterologous expression of these candidates and activity testing led to the identification of a novel P450 that efficiently converts ritonavir resembling the activity of the human CYP3A4.

The effect of ritonavir on human CYP2B6 catalytic activity: Heme modification contributes to the mechanism-based inactivation of CYP2B6 and CYP3A4 by ritonavir

The mechanism-based inactivation of human CYP2B6 by ritonavir (RTV) in a reconstituted system was investigated. The inactivation is time, concentration, and NADPH dependent and exhibits a Kl of 0.9 μM, a k inact of 0.05 min-1, and a partition ratio of approximately 3. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed that the protonated molecular ion of RTV exhibits an m/z at 721 and its two major metabolites are an oxidation product with MH+ at m/z 737 and a deacylated product with MH+at m/z 580. Inactivation of CYP2B6 by incubation with 10 μM RTV for 10 min resulted in an approximately 50% loss of catalytic activity and native heme, but no modification of the apoprotein was observed. RTV was found to be a potent mixed-type reversible inhibitor (Ki = 0.33 μM) and a type II ligand (spectral dissociation constant-Ks = 0.85 mM) of CYP2B6. Although previous studies have demonstrated that RTV is a potent mechanism-based inactivator of CYP3A4, the molecular mechanism responsible for the inactivation has not been determined. Here, we provide evidence that RTV inactivation of CYP3A4 is due to heme destruction with the formation of a heme-protein adduct. Similar to CYP2B6, there is no significant modification of the apoprotein. Furthermore, LC-MS/MS analysis revealed that both CYP3A4 and human liver microsomes form an RTV-glutathione conjugate having a MH+ at m/z 858 during metabolism of RTV, suggesting the formation of an isocyanate intermediate leading to formation of the conjugate. Copyright