ritonavir   Click here for help

GtoPdb Ligand ID: 8804

Abbreviated name: RTV
Synonyms: A-84538 | ABBOTT-84538 | ABT 538 | ABT-538 | Norvir®
Approved drug PDB Ligand
ritonavir is an approved drug (EMA & FDA (1996))
Compound class: Synthetic organic
Comment: Ritonavir is an orally bioavailable antiviral that is generally administered in combination with other anti-HIV or anti-HCV drugs.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 11
Hydrogen bond donors 4
Rotatable bonds 22
Topological polar surface area 202.26
Molecular weight 720.31
XLogP 3.94
No. Lipinski's rules broken 2
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Canonical SMILES O=C(NC(C(CC(Cc1ccccc1)NC(=O)C(C(C)C)NC(=O)N(Cc1csc(n1)C(C)C)C)O)Cc1ccccc1)OCc1cncs1
Isomeric SMILES O=C(N[C@H]([C@H](C[C@H](Cc1ccccc1)NC(=O)[C@H](C(C)C)NC(=O)N(Cc1csc(n1)C(C)C)C)O)Cc1ccccc1)OCc1cncs1
InChI InChI=1S/C37H48N6O5S2/c1-24(2)33(42-36(46)43(5)20-29-22-49-35(40-29)25(3)4)34(45)39-28(16-26-12-8-6-9-13-26)18-32(44)31(17-27-14-10-7-11-15-27)41-37(47)48-21-30-19-38-23-50-30/h6-15,19,22-25,28,31-33,44H,16-18,20-21H2,1-5H3,(H,39,45)(H,41,47)(H,42,46)/t28-,31-,32-,33-/m0/s1
Bioactivity Comments
Inhibition of CYP3A4 by ritonavir blocks this metabolizing enzyme form breaking down other antiviral protease inhibitors, and in so-doing enhances the activity of the other protease inhibitors it is administered with. This activity means that potentially dangerous pharmacokinetic interactions are likely if ritonavir is administered with other drugs that are inhibitors of CYP3A (and also of CYP2D6) e.g. alfuzosin, amiodarone, cisapride, ergot alkaloids, flecainide, lovastatin, oral midazolam, pimozide, propafenone, quinidine, sildenafil, simvastatin and triazolam. St. John's wort is a CYP3A inducer that can decrease substrate drug levels to sub-therapeutic concentrations.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
CYP3A4 Hs Inhibitor Inhibition >7.0 pKi - 2
pKi >7.0 (Ki <1x10-7 M) [2]
CYP3A5 Hs Inhibitor Inhibition 6.9 pKi - 1
pKi 6.9 (Ki 1.2x10-7 M) [1]
UDP glucuronosyltransferase family 1 member A1 Hs Inhibitor Inhibition 5.8 pIC50 - 4
pIC50 5.8 (IC50 1.7x10-6 M) Both inhibitor and substrate [4]