Ritonavir
Catalog No.S1185 Synonyms: ABT-538, A 84538
Molecular Weight(MW): 720.94
Ritonavir is a Cytochrome P450 3A and Protease Inhibitor; Also inhibits Cytochrome P450 2D6, P-Glycoprotein and induces Cytochrome P450 2C19, Cytochrome P450 1A2, Cytochrome P450 2C9, Cytochrome P450 2B6 and UDP Glucuronosyltransferases.
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(A) KMS11 and (B) L363 cells were plated in 5mM glucose medium with ritonavir or DMSO (D) for 17 hours. Glucose consumption rates are normalized to untreated cells (not shown). (C) KMS11 and (D) L363 cells were treated with ritonavir or DMSO for 72 hours. Relative viable cell numbers were determined by MTS assay and normalized to untreated cells (not shown).
Blood 2012 119, 4686-97. Ritonavir purchased from Selleck.
Primary myeloma cells were treated with DMSO or ritonavir for 72 hours before annexin V/DAPI staining. Values are normalized to DMSO-treated samples (n=1 for each patient sample).
Blood 2012 119, 4686-97. Ritonavir purchased from Selleck.
Purity & Quality Control
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Biological Activity
| Description | Ritonavir is a Cytochrome P450 3A and Protease Inhibitor; Also inhibits Cytochrome P450 2D6, P-Glycoprotein and induces Cytochrome P450 2C19, Cytochrome P450 1A2, Cytochrome P450 2C9, Cytochrome P450 2B6 and UDP Glucuronosyltransferases. | ||
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| Targets |
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| In vitro |
Ritonavir is a very potent inhibitor of CYP3A4 mediated testosterone 6β-hydroxylation with mean Ki of 19 nM and also inhibits tolbutamide hydroxylation with IC50 of 4.2 μM. [1] Ritonavir is found to be a potent inhibitor of CYP3A-mediated biotransformations (nifedipine oxidation with IC50 of 0.07 mM, 17alpha-ethynylestradiol 2-hydroxylation with IC50 of 2 mM; terfenadine hydroxylation with IC50 of 0.14 mM). Ritonavir is also found to be an inhibitor of the reactions mediated by CYP2D6 (IC50 = 2.5 mM) and CYP2C9/10 (IC50 = 8.0 mM). [2] Ritonavir results in an increase in cell viability in uninfected human PBMC cultures. Ritonavir markedly decreases the susceptibility of PBMCs to apoptosis correlated with lower levels of caspase-1 expression, decreases in annexin V staining, and reduces caspase-3 activity in uninfected human PBMC cultures. Ritonavir inhibits induction of tumor necrosis factor (TNF) production by PBMCs and monocytes in a time- and dose-dependent manner at nontoxic concentrations. [3] Ritonavir inhibits p-glycoprotein-mediated extrusion of saquinavir with an IC50 of 0.2 μM, indicating a high affinity of ritonavir for p-glycoprotein. [4] Ritonavir inhibits human liver microsomal metabolism of ABT-378 potently with Ki of 13 nM. Ritonavir combined with ABT-378 (at 3:1 and 29:1 ratios) inhibits CYP3A (IC50 = 1.1 and 4.6 μM), albeit less potently than Ritonavir (IC50 = 0.14 μM). [5] |
Protocol
Solubility (25°C)
| In vitro | DMSO | 100 mg/mL (138.7 mM) |
|---|---|---|
| Ethanol | 3 mg/mL (4.16 mM) | |
| Water | Insoluble | |
| In vivo | Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 30% PEG400+0.5% Tween80+5% propylene glycol For best results, use promptly after mixing. |
30 mg/mL |
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Information
| Molecular Weight | 720.94 |
|---|---|
| Formula | C37H48N6O5S2 |
| CAS No. | 155213-67-5 |
| Storage | powder |
| in solvent | |
| Synonyms | ABT-538, A 84538 |
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Clinical Trial Information
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT02968641 | Not yet recruiting | Chronic Delta Hepatitis | Eiger BioPharmaceuticals | October 2019 | Phase 2 |
| NCT02968641 | Not yet recruiting | Chronic Delta Hepatitis | Eiger BioPharmaceuticals | October 2019 | Phase 2 |
| NCT03675815 | Not yet recruiting | HIV Infections | Kirby Institute | April 15 2019 | Phase 4 |
| NCT03675815 | Not yet recruiting | HIV Infections | Kirby Institute | April 15 2019 | Phase 4 |
| NCT03719313 | Recruiting | Hepatitis Delta Virus | Eiger BioPharmaceuticals | December 1 2018 | Phase 3 |
| NCT03719313 | Recruiting | Hepatitis Delta Virus | Eiger BioPharmaceuticals | December 1 2018 | Phase 3 |
Tech Support
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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