PhiKan 083

PhiKan 083 is a carbazole derivative, which binds to the surface cavity and stabilizes Y220C (a p53 mutant), with a Kd of 167 μM measured by NMR[1], and a relative binding affinity (Kd) of 150 μM in Ln229 cells[3].

Signaling Pathways >> Apoptosis >> MDM-2/p53

Research Areas >> Cancer

Kd: 167 μM (p53-Y220C)[1], 150 μM (p53Y220C, in Ln229 cells)[3]

PhiKan 083 is a carbazole derivative, which binds to the surface cavity and stabilizes Y220C (a p53 mutant), with a Kd of 167 μM measured by NMR[1], shows a relative binding affinity (Kd) of 150 μM for p53Y220C in Ln229 cells[3]. PhiKan083 slows down its thermal denaturation rate[2]. PhiKan 083 (125 μM) reduces the cell viability of engineered variants of Ln229 cells. PhiKan 083 (100 μM) in conbination with doxorubicin (1 μM) enhances the pro-apoptotic activity in all variants of Ln229 cells (p535, p53Y220C, p53G245S, p53R282W)[3].

[1]. Boeckler FM, et al. Targeted rescue of a destabilized mutant of p53 by an in silico screened drug. Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10360-5.

[2]. Rauf SM, et al. Effect of Y220C mutation on p53 and its rescue mechanism: a computer chemistry approach. Protein J. 2013 Jan;32(1):68-74.

[3]. Paulmurugan R, et al. A protein folding molecular imaging biosensor monitors the effects of drugs that restore mutant p53 structure and its downstream function in glioblastoma cells. Oncotarget. 2018 Apr 20;9(30):21495-21511.

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