PK11007

• CAT Number: I012909
• CAS Number: 38275-34-2
• Molecular Formula: C₆H₅ClN₂O₄S
• Molecular Weight: 236.63
• Purity: ≥95%
• Target: p53
• Solubility: DMSO
• IUPAC Name: 5-chloro-2-methylsulfonylpyrimidine-4-carboxylic acid
• InChI: InChI=1S/C6H5ClN2O4S/c1-14(12,13)6-8-2-3(7)4(9-6)5(10)11/h2H,1H3,(H,10,11)
• InChIKey: WZUPWJVRWIVWEF-UHFFFAOYSA-N
• SMILES: CS(=O)(=O)C1=NC=C(C(=N1)C(=O)O)Cl

PK11007 (CAT: I012909) is a small molecule compound that has been investigated for its potential anticancer properties. It has been shown to exhibit cytotoxic activity against various cancer cell lines, including breast, lung, colon, and prostate cancer cells. PK11007 has been reported to induce apoptosis, inhibit cell proliferation, and inhibit angiogenesis, suggesting its potential as an anticancer agent. However, further research is needed to fully understand its mechanism of action and evaluate its efficacy and safety profile for potential therapeutic applications.

Reference

1. Cancer Lett. 2018 Feb 1;414:99-106. doi: 10.1016/j.canlet.2017.09.053. Epub 2017 Oct 22.
Mutant p53 as a therapeutic target for the treatment of triple-negative breast cancer: Preclinical investigation with the anti-p53 drug, PK11007.
Synnott NC(1), Bauer MR(2), Madden S(3), Murray A(1), Klinger R(4), O'Donovan N(5), O'Connor D(6), Gallagher WM(4), Crown J(7), Fersht AR(2), Duffy MJ(8).
Author information:
(1)UCD School of Medicine, University College Dublin, Dublin 4, Ireland. (2)Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom. (3)Population Health Sciences, Department of Psychology, Royal College of Surgeons in Ireland, Dublin, Ireland. (4)UCD School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin 4, Ireland. (5)National Institute for Cellular Biotechnology (NICB), Dublin City University, Dublin, Ireland. (6)Department of Molecular & Cellular Therapeutics, Royal College of Surgeons Ireland, Dublin, Ireland. (7)Department of Medical Oncology, St Vincent's University Hospital, Dublin 4, Ireland. (8)UCD School of Medicine, University College Dublin, Dublin 4, Ireland; UCD Clinical Research Centre, St. Vincent's University Hospital, Dublin 4, Ireland. Electronic address: .
The identification of a targeted therapy for patients with triple-negative breast cancer (TNBC) is one of the most urgent needs in breast cancer therapeutics. The p53 gene is mutated in approximately 80% of patients with TNBC, and is a potential therapeutic target for patients with this form of breast cancer. The 2-sulfonylpyrimidine compound, PK11007, preferentially decreases viability in p53-compromised cancer cell lines. We investigated PK11007 as a potential new treatment for TNBC. IC50 values for inhibition of proliferation in a panel of 17 breast cell lines by PK11007 ranged from 2.3 to 42.2 μM. There were significantly lower IC50 values for TNBC than for non-TNBC cell lines (p = 0.03) and for p53-mutated cell lines compared with p53 WT cells (p = 0.003). Response to PK11007 however, was independent of the estrogen receptor (ER) or HER2 status of the cell lines. In addition to inhibiting cell proliferation, PK11007 induced apoptosis in p53 mutant cell lines. Using RNAseq and gene ontology analysis, we found that PK11007 altered the expression of genes enriched in pathways involved in regulated cell death, regulation of apoptosis, signal transduction, protein refolding and locomotion. The observations that PK11007 inhibited cell proliferation, induced apoptosis and altered genes involved in cell death are all consistent with the ability of PK11007 to reactivate mutant p53. Based on our data, we conclude that targeting mutant p53 with PK11007 is a potential approach for treating p53-mutated breast cancer, including the subgroup with TN disease.