YHO-13177

• CAT Number: I005436
• CAS Number: 912287-56-0
• Molecular Formula: C20H22N2O3S
• Molecular Weight: 370.47
• Purity: ≥95%
• Synonyms: (Z)-2-(3,4-dimethoxyphenyl)-3-[5-(4-hydroxypiperidin-1-yl)thiophen-2-yl]prop-2-enenitrile
• InChI: InChI=1S/C20H22N2O3S/c1-24-18-5-3-14(12-19(18)25-2)15(13-21)11-17-4-6-20(26-17)22-9-7-16(23)8-10-22/h3-6,11-12,16,23H,7-10H2,1-2H3/b15-11+
• InChIKey: NOGGBVNCVONHHC-RVDMUPIBSA-N
• SMILES: COC1=C(C=C(C=C1)C(=CC2=CC=C(S2)N3CCC(CC3)O)C#N)OC

YHO-13177 is a potent and specific inhibitor of BCRP; potentiated the cytotoxicity of SN-38 in cancer cells and no effect on P-glycoprotein–mediated paclitaxel resistance in MDR1-transduced human leukemia K562 cells.
IC50 value:
Target: BCRP inhibitor
in vitro: YHO-13177 potentiated the cytotoxicity of SN-38, mitoxantrone, and topotecan in both BCRP-transduced human colon cancer HCT116 (HCT116/BCRP) cells and SN-38–resistant human lung cancer A549 (A549/SN4) cells that express BCRP, but had little effect in the parental cells. In addition, YHO-13177 potentiated the cytotoxicity of SN-38 in human lung cancer NCI-H460 and NCI-H23, myeloma RPMI-8226, and pancreatic cancer AsPC-1 cells that intrinsically expressed BCRP. In contrast, it had no effect on P-glycoprotein–mediated paclitaxel resistance in MDR1-transduced human leukemia K562 cells and multidrug resistance-related protein 1–mediated doxorubicin resistance in MRP1-transfected human epidermoid cancer KB-3-1 cells. YHO-13177 increased the intracellular accumulation of Hoechst 33342, a substrate of BCRP, at 30 minutes and partially suppressed the expression of BCRP protein at more than 24 hours after its treatment in both HCT116/BCRP and A549/SN4 cells [1].
in vivo: In mice, YHO-13351 was rapidly converted into YHO-13177 after its oral or intravenous administration. Coadministration of irinotecan with YHO-13351 significantly increased the survival time of mice inoculated with BCRP-transduced murine leukemia P388 cells and suppressed the tumor growth in an HCT116/BCRP xenograft model, whereas irinotecan alone had little effect in these tumor models [1].

Reference

[1]. Yamazaki R, et al. Novel acrylonitrile derivatives, YHO-13177 and YHO-13351, reverse BCRP/ABCG2-mediated drug resistance in vitro and in vivo. Mol Cancer Ther. 2011 Jul;10(7):1252-63.
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