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HsClpP activator ZK53

Chemical Structure : HsClpP activator ZK53

CAS No.: 3031789-26-8

HsClpP activator ZK53 (ZK53)

Catalog No.: PC-21313Not For Human Use, Lab Use Only.

HsClpP activator ZK53 is a potent, selective activator of mitochondrial caseinolytic protease P (HsClpP) with EC50 of 0.22 uM in FI-based protease activity assays, inactive toward bacterial ClpP proteins.

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Purity & Documentation Purity: >98% (HPLC) Select Batch:

Biological Activity

HsClpP activator ZK53 is a potent, selective activator of mitochondrial caseinolytic protease P (HsClpP) with EC50 of 0.22 uM in FI-based protease activity assays, inactive toward bacterial ClpP proteins.
ZK53 selectively binds and stabilizes HsClpP rather than SaClpP in vitro.
ZK53 potently inhibits Lung squamous cell carcinoma (LUSC) cell proliferation with GI50 of 0.5-1 uM, also inhibits cell proliferation in the clonogenic assay and the time-dependent MTT assays, but does not induce cell apoptosis in human lung fibroblast MRC-5 cells.
ZK53 impairs mitochondrial functions and targets HsClpP in LUSC cells, ZK53 triggers a substantial reduction in multiple ETC subunits, including NDUFB8, SDHA, UQCRC2, and COXIV in a dose-dependent manner, also reduces the protein abundances of TFAM, TUFM, and ACO2 in H1703 cells.
ZK53 treatment (1 uM) significantly downregulates the E2F targets in H1703 cells, impairs the essential regulatory pathways for the G1/S transition.
ZK53 activates the ataxia-telangiectasia mutated (ATM)-mediated DNA damage response in H1703 cells.
ZK53 ( 80 mg/kg, dissolved in 40% 2-hydroxypropyl-β-cyclodextrin, i.p. twice a day) exhibits anticancer activity in xenograft and autochthonous mouse models.

Physicochemical Properties

M.Wt 424.29
Formula C19H20BrF2N3O
Appearance Solid
CAS No.
Storage
Solide Powder
-20°C 12 Months; 4°C 6 Months
In Solvent
-80°C 6 Months; -20°C 6 Months
Shipping
Solubility

10 mM in DMSO

Chemical Name/SMILES

N-(4-bromobenzyl)-4-(3,5-difluorobenzyl)piperazine-1-carboxamide

References

1. Zhou LL, et al. Nat Commun. 2023 Nov 3;14(1):7069.

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