RO-0335

• CAS: 867365-76-2
• Catalog Number: ACM867365762
• Category: Inhibitors
• Molecular Weight: 573.22
• Molecular Formula: C21H13BrCl2FN3O4S
• Description: RO-0335 is a novel diphenylether nonnucleoside reverse transcriptase inhibitor. 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.
• Synonyms: RO0335; RO-0335; RO 0335
• IUPAC Name: 2-(4-bromo-3-(3-chloro-5-cyanophenoxy)-2-fluorophenyl)-N-(2-chloro-4-sulfamoylphenyl)acetamide
• Canonical SMILES: O=C(NC1=CC=C(S(=O)(N)=O)C=C1Cl)CC2=CC=C(Br)C(OC3=CC(C#N)=CC(Cl)=C3)=C2F
• 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)
• InChI Key: SBUUICLVCQQMFP-UHFFFAOYSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >5 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: RO-0335 is a novel diphenylether nonnucleoside reverse transcriptase inhibitor.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 44.00; H, 2.29; Br, 13.94; Cl, 12.37; F, 3.31; N, 7.33; O, 11.16; S, 5.59
• Exact Mass: 570.91712
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: 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.; Reference: 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. In vitro resistance development for RO-0335, a novel diphenylether nonnucleoside reverse transcriptase inhibitor. Antiviral Res. 2010 May;86(2):212-9. doi: 10.1016/j.antiviral.2010.02.323. Epub 2010 Feb 26. PMID: 20219553.
• In Vivo Activity: TBD
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).