A8203-10mg | Ritonavir [155213-67-5] Clinisciences

Background

Ritonavir, previously known as ABT-538, is a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) protease that exhibits potent in vitro inhibition against HIV-1 strain as well as HIV-2 strain with 50% effective concentration EC₅₀ values of 0.022 μM and 0.16 μM respectively. Ritonavir binds to the HIV-1 protease inactivating its function to cleave the Gag and Gag-Pol polyproteins into the core proteins and viral enzymes, which results in the formation of noninfectious viral particles. X-ray crystallographic analysis reveals a hydrophobic cluster between the isopropyl substituent on the P3 thiazolyl group of ritonavir and the side chains of Pro-81 and Val-82 of HIV-1 protease within the complex of ritonavir/HIV-1 protease.

Reference

Kempf DJ, Marsh KC, Denissen JF, McDonald E, Vasavanonda S, Flentge CA, Green BE, Fino L, Park CH, Kong XP, et al. ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2484-8.

Markowitz M, Saag M, Powderly WG, Hurley AM, Hsu A, Valdes JM, Henry D, Sattler F, La Marca A, Leonard JM, et al. A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection. N Engl J Med. 1995 Dec 7;333(23):1534-9.

Product Citation

1. Lorela Paço, John C Hackett, et al. "Nanodisc-embedded cytochrome P450 P3A4 binds diverse ligands by distributing conformational dynamics to its flexible elements." J Inorg Biochem. 2023 Jul:244:112211. PMID: 37080138

Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	720.9
Cas No.	155213-67-5
Formula	C₃₇H₄₈N₆O₅S₂
Synonyms	Abbott 84538, ABT-538,Ritonavir
Solubility	≥26 mg/mL in DMSO with gentle warming; insoluble in H2O; ≥9.02 mg/mL in EtOH
Chemical Name	1,3-thiazol-5-ylmethyl N-[(2S,3S,5S)-3-hydroxy-5-[[(2S)-3-methyl-2-[[methyl-[(2-propan-2-yl-1,3-thiazol-4-yl)methyl]carbamoyl]amino]butanoyl]amino]-1,6-diphenylhexan-2-yl]carbamate
SDF	Download SDF
Canonical SMILES	CC(C)C1=NC(=CS1)CN(C)C(=O)NC(C(C)C)C(=O)NC(CC2=CC=CC=C2)CC(C(CC3=CC=CC=C3)NC(=O)OCC4=CN=CS4)O
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Anti-virus experiment [1]:
Viruses	HIV
Preparation method	The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.
Reacting condition	0 ~ 0.16 μM
Applications	Ritonavir potently inhibited the activity of laboratory and clinical strains of HIV-1 with the EC50 values ranging from 0.022 to 0.13 μM. Moreover, Ritonavir also efficiently inhibited the activity of HIV-2, with the EC50 value of 0.16 μM.
Animal experiment [1]:
Animal models	Male SD rats
Dosage form	10 mg/kg; p.o.
Applications	In rats, oral administration of 10 mg/kg Ritonavir resulted in prolonged absorption (tmax = 2.0 hrs). The peak of plasma Ritonavir concentration was > 100 folds of the EC50 value. The calculated oral bioavailability reached 78%.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Kempf DJ, Marsh KC, Denissen JF, McDonald E, Vasavanonda S, Flentge CA, Green BE, Fino L, Park CH, Kong XP, et al. ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2484-8.

Biological Activity

Description	Ritonavir is an antiretroviral (HIV) drug and inhibitor of particular liver enzyme that normally metabolizes protease inhibitors, cytochrome P450-3A4 (CYP3A4).
Targets	HIV Protease
IC50