NSC59984

In the corresponding groups, moxibustion treatment was carried out using cigarette-like moxa strips that were suspended near "Shenshu" (BL23) and "Zusanli" (ST36) once daily for 15 days, and the p53 agonist NSC59984 was administered intraperitoneally...The levels of SLC7A11, GPX4, and GSH were the opposite. Moxibustion can improve RA synovial inflammatory injury by regulating ferroptosis through inhibition of p53 protein expression.

In our previous study, co-treatment with p73 activator NSC59984 and NAMPT inhibitor FK886 synergistically repressed Detroit 562 cell proliferation...Moreover, NAMPT was repressed by chlorophyllides independent of p73 status in vivo. We thus concluded that chlorophyllides have a dual anticancer function when applied to HNSCC cells with p53 gain-of-function mutation, via activation of p73 and repression of p53 aggregation.

One of these p53 reactivator molecules, NSC 59984, reduced expression of GPX4, which is unlikely to explain its ability to reduce sensitivity to ferroptosis. We suggest that these p53 reactivators function via an unknown, p53-independent manner to suppress ferroptosis.

Cotreatment of THP-1 cells with venetoclax and a TP53 activator NSC59984 downregulated DRP1 expression and increased apoptosis. These findings suggest that DRP1 is functionally associated with venetoclax sensitivity in TP53-mutated AML cells. Targeting DRP1 may represent an effective therapeutic strategy for overcoming venetoclax resistance in TP53-mutated AML.

Overall, these findings demonstrate p53-dependent effects of NSC59984 on cellular metabolism, with increased activity in cells harboring the p53 R248W mutation. This research highlights the importance of defining the mutational status of a particular cancer to create a patient-centric strategy for the treatment of p53-driven cancers.