Synonym
PK11007; PK-11007; PK 11007;
IUPAC/Chemical Name
5-chloro-2-((4-fluorobenzyl)sulfonyl)-N-(5-methyl-1,3,4-thiadiazol-2-yl)pyrimidine-4-carboxamide
InChi Key
IVZQUWCWXYFPOQ-UHFFFAOYSA-N
InChi Code
InChI=1S/C15H11ClFN5O3S2/c1-8-21-22-14(26-8)20-13(23)12-11(16)6-18-15(19-12)27(24,25)7-9-2-4-10(17)5-3-9/h2-6H,7H2,1H3,(H,20,22,23)
SMILES Code
O=C(C1=NC(S(=O)(CC2=CC=C(F)C=C2)=O)=NC=C1Cl)NC3=NN=C(C)S3
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
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
Biological target:
PK11007 is an anti-p53 drug.
In vitro activity:
This study found certain 2-sulfonylpyrimidines, including one named PK11007, to be mild thiol alkylators with anticancer activity in several cell lines, especially those with mutationally compromised p53. PK11007 acted by two routes: p53 dependent and p53 independent. PK11007 stabilized p53 in vitro via selective alkylation of two surface-exposed cysteines without compromising its DNA binding activity. Unstable p53 was reactivated by PK11007 in some cancer cell lines, leading to up-regulation of p53 target genes such as p21 and PUMA.
Reference: Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):E5271-80. https://pubmed.ncbi.nlm.nih.gov/27551077/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
250.0 |
584.31 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
427.85
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Synnott NC, Bauer MR, Madden S, Murray A, Klinger R, O'Donovan N, O'Connor D, Gallagher WM, Crown J, Fersht AR, Duffy MJ. 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. doi: 10.1016/j.canlet.2017.09.053. Epub 2017 Oct 22. PMID: 29069577.
2. Bauer MR, Joerger AC, Fersht AR. 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. doi: 10.1073/pnas.1610421113. Epub 2016 Aug 22. PMID: 27551077; PMCID: PMC5018792.
In vitro protocol:
1. Synnott NC, Bauer MR, Madden S, Murray A, Klinger R, O'Donovan N, O'Connor D, Gallagher WM, Crown J, Fersht AR, Duffy MJ. 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. doi: 10.1016/j.canlet.2017.09.053. Epub 2017 Oct 22. PMID: 29069577.
2. Bauer MR, Joerger AC, Fersht AR. 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. doi: 10.1073/pnas.1610421113. Epub 2016 Aug 22. PMID: 27551077; PMCID: PMC5018792.
1: Duffy MJ, Synnott NC, Crown J. Mutant p53 in breast cancer: potential as a therapeutic target and biomarker. Breast Cancer Res Treat. 2018 Jul;170(2):213-219. doi: 10.1007/s10549-018-4753-7. Epub 2018 Mar 21. Review. PubMed PMID: 29564741.
2: Synnott NC, Bauer MR, Madden S, Murray A, Klinger R, O'Donovan N, O'Connor D, Gallagher WM, Crown J, Fersht AR, Duffy MJ. 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. doi: 10.1016/j.canlet.2017.09.053. Epub 2017 Oct 22. PubMed PMID: 29069577.
3: Duffy MJ, Synnott NC, Crown J. Mutant p53 as a target for cancer treatment. Eur J Cancer. 2017 Sep;83:258-265. doi: 10.1016/j.ejca.2017.06.023. Epub 2017 Jul 28. Review. PubMed PMID: 28756138.
4: Bauer MR, Joerger AC, Fersht AR. 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. doi: 10.1073/pnas.1610421113. Epub 2016 Aug 22. PubMed PMID: 27551077; PubMed Central PMCID: PMC5018792.
