RO-0335

• CAT Number: I009058
• CAS Number: 867365-76-2
• Molecular Formula: C21H13BrCl2FN3O4S
• Molecular Weight: 573.22
• Purity: ≥95%
• Solubility: Soluble in DMSO
• Storage: Store at -20°C
• IUPAC Name: 2-[4-bromo-3-(3-chloro-5-cyanophenoxy)-2-fluorophenyl]-N-(2-chloro-4-sulfamoylphenyl)acetamide
• InChI: InChI=1S/C21H13BrCl2FN3O4S/c22-16-3-1-12(20(25)21(16)32-14-6-11(10-26)5-13(23)8-14)7-19(29)28-18-4-2-15(9-17(18)24)33(27,30)31/h1-6,8-9H,7H2,(H,28,29)(H2,27,30,31)
• InChIKey: SBUUICLVCQQMFP-UHFFFAOYSA-N
• SMILES: C1=CC(=C(C=C1S(=O)(=O)N)Cl)NC(=O)CC2=C(C(=C(C=C2)Br)OC3=CC(=CC(=C3)C#N)Cl)F

RO-0335（Cat No.:I009058） is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that belongs to the diphenyl ether class of compounds. It is a small molecule that binds to the reverse transcriptase enzyme of the human immunodeficiency virus (HIV) and inhibits its activity. Specifically, it targets a hydrophobic pocket in the enzyme, which leads to a conformational change that inhibits reverse transcription and viral replication.

Reference

1:Antiviral Res. 2010 May;86(2):212-9. doi: 10.1016/j.antiviral.2010.02.323. Epub 2010 Feb 26. In vitro resistance development for RO-0335, a novel diphenylether nonnucleoside reverse transcriptase inhibitor.Javanbakht H,Ptak RG,Chow E,Yan JM,Russell JD,Mankowski MK,Hogan PA,Hogg JH,Vora H,Hang JQ,Li Y,Su G,Paul A,Cammack N,Klumpp K,Heilek G, PMID: 20219553 DOI: 10.1016/j.antiviral.2010.02.323 Abstract: Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are important components of current combination therapies for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. However, their low genetic barriers against resistance development, cross-resistance and serious side effects can compromise the benefits of the first generation compounds in this class (efavirenz and nevirapine). To study potential pathways leading to resistance against the novel diphenylether NNRTI, RO-0335, sequential passage experiments at low multiplicity of infection (MOI) were performed to solicit a stepwise selection of resistance mutations. Two pathways to loss of susceptibility to RO-0335 were observed, containing patterns of amino acid changes at either V106I/A plus F227C (with additional contributions from A98G, V108I, E138K, M230L and P236L) or V106I/Y188L (with a potential contribution from L100I, E138K and Y181C). Characterization of the observed mutations by site-directed mutagenesis in the isogenic HXB2D background demonstrated that a minimum of two or more mutations were required for significant loss of susceptibility, with the exception of Y188L, which requires a two-nucleotide change. Patterns containing F227C or quadruple mutations selected by RO-0335 showed a low relative fitness value when compared to wild-type HXB2D.