YHO-13351
Names
[ CAS No. ]:
1346753-00-1
[ Name ]:
YHO-13351
[Synonym ]:
Glycine, N,N-diethyl-, 1-[5-[(Z)-2-cyano-2-(3,4-dimethoxyphenyl)ethenyl]-2-thienyl]-4-piperidinyl ester, methanesulfonate (1:1)
1-{5-[(Z)-2-Cyano-2-(3,4-dimethoxyphenyl)vinyl]-2-thienyl}-4-piperidinyl N,N-diethylglycinate methanesulfonate (1:1)
Biological Activity
[Description]:
YHO-13351 is the water-soluble prodrug of YHO-13177, which is a potent and specific inhibitor of BCRP.IC50 value:Target: BCRP inhibitorin 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].
[Related Catalog]:
[References]
[Related Small Molecules]
Chemical & Physical Properties
[ Molecular Formula ]:
C27H37N3O7S2
[ Molecular Weight ]:
579.729
[ Exact Mass ]:
579.207275
[ Storage condition ]:
2-8℃