PK11007

Names

[ Name ]:
PK11007

[Synonym ]:
2-methanesulfonyl-5-chloro-4-pyrimidinecarboxylic acid
2-methylsulfonyl-5-chloro-4-pyrimidine carboxylic acid
2-methylsulfonyl-5-chloropyrimidine-4-carboxylic acid
5-chloro-2-methanesulfonyl-pyrimidine-4-carboxylic acid
4-carboxy-5-chloro-2-methylsulfonylpyrimidine
PK11007

Biological Activity

[Description]:

PK11007 is a p53 targeting compound, has anti-tumor activities through activation of unstable p53.

[Related Catalog]:

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

Research Areas >> Cancer

[Target]

p53[1]

[In Vitro]

PK11007 (15-30 µM) reduces the viability of mutant p53 cell lines MKN1 (V143A), HUH-7 (Y220C), NUGC-3 (Y220C), and SW480 (R273H/P309S). PK11007 also shows inhibitory activities against the p53 wt cancer cell lines HUH-6 and NUGC-4, as well as the fibroblast cell line WI-38 only at high concentrations (60 and 120 µM). PK11007 increases levels of p53 target genes and activates the unfolded protein response pathway. PK11007 also increases p53 activity in HUH-6 and NUGC-4 cells. PK11007 induces cell death via caspase-independent pathways. PK11007 (30, 60 µM) induces reactive oxygen species (ROS) especially in mutant p53 cells[1]. PK11007 inhibits the proliferation of a panel of 17 breast cell lines, with IC50s ranging from 2.3 to 42.2 μM[2].

[Cell Assay]

Cell viability is measured using the CellTiter-Fluor cell viability assay kit. Cells are seeded in 96-well plates at 7,500-15,000 cells per well and incubated overnight. Samples are prepared in medium with a twice-as-high compound (including PK11007), and DMSO concentration then added to an equivalent volume of growth medium, yielding a final DMSO concentration of 0.5%. After incubating of cells for 23 h or the respective time period, CellTiter-Fluor reagent is added to each well and incubated again for 45 min. Fluorescence is then recorded on a PHERAstar plate reader using 400/500 nm excitation/emission filters. Experiments are performed in quadruplicate[1].

[References]

[1]. Bauer MR, et al. 2-Sulfonylpyrimidines: Mild alkylating agents with anticancer activity toward p53-compromised cells. Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):E5271-80.

[2]. Synnott NC, et al. Mutant p53 as a therapeutic target for the treatment of triple-negative breast cancer: Preclinical investigation with the anti-p53 drug, PK11007. Cancer Lett. 2018 Feb 1;414:99-106

[Related Small Molecules]

Pifithrin-α hydrobromide | RG7388 | Nutlin-3a | AMG232 | Pifithrin-β (hydrobromide) | Stylomycin aminonucleoside | RG7112 | APR-246 | NVP-HDM201 | SAR 405838 | RITA (NSC 652287) | NVP-CGM097 | Tenovin-1 | SJ 172550

Chemical & Physical Properties

[ Molecular Formula ]:
C₆H₅ClN₂O₄S

[ Molecular Weight ]:
236.63300

[ Exact Mass ]:
235.96600

[ PSA ]:
105.60000

[ LogP ]:
1.31250

[ Storage condition ]:
-20℃

Safety Information

[ HS Code ]:
2933599090

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933599090

[ Summary ]:
2933599090. other compounds containing a pyrimidine ring (whether or not hydrogenated) or piperazine ring in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%