PK11000 is a novel and potent p53-targeting chemical with alkylating properties that has anti-tumor effects by activating unstable p53 (tumor suppressor p53). There were two ways that PK11000 operated: p53 dependent and p53 independent. By selectively alkylating two surface-exposed cysteines, PK11000 preserved the DNA binding activity of p53 while stabilizing it in vitro. In some cancer cell lines, PK11000 reactivated unstable p53, which increased the expression of p53 target genes like p21 and PUMA. More generally, as was also observed for the anticancer drug PRIMA-1(MET)(APR-246), there was cell death that was independent of p53 but dependent on glutathione depletion and associated with highly elevated levels of reactive oxygen species and induction of endoplasmic reticulum (ER) stress. PK11000 may serve as a lead for anticancer medications that target cells with dysfunctional p53 or impaired reactive oxygen species (ROS) detoxification in a variety of mutant p53 cells.

Physicochemical Properties

Molecular Formula	C6H5CLN2O4S
Molecular Weight	236.63
Exact Mass	235.966
Elemental Analysis	C, 30.46; H, 2.13; Cl, 14.98; N, 11.84; O, 27.05; S, 13.55
CAS #	38275-34-2
Related CAS #	38275-34-2
PubChem CID	1241459
Appearance	White to off-white solid powder
LogP	1.312
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	2
Heavy Atom Count	14
Complexity	325
Defined Atom Stereocenter Count	0
SMILES	ClC1=C([H])N=C(N=C1C(=O)O[H])S(C([H])([H])[H])(=O)=O
InChi Key	WZUPWJVRWIVWEF-UHFFFAOYSA-N
InChi Code	InChI=1S/C6H5ClN2O4S/c1-14(12,13)6-8-2-3(7)4(9-6)5(10)11/h2H,1H3,(H,10,11)
Chemical Name	5-chloro-2-methylsulfonylpyrimidine-4-carboxylic acid
Synonyms	PK 11007-analog; PK-11007-analog; PK11007-analog; PK11000; PK-11000; PK 11000
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	p53
ln Vitro	PK11000 (0-120 μM, 24 h) only slightly inhibits cancer cells with mutant p53[1]. PK11000 (0-50 μM, 5 d) shows anti-proliferation effects of breast cell lines[2].
References	[1]. 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]. 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.

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 40mg/mL Water: ≥ 40mg/mL Ethanol: ≥ 20mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (10.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 20 mg/mL (84.52 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.2260 mL	21.1300 mL	42.2601 mL
	5 mM	0.8452 mL	4.2260 mL	8.4520 mL
	10 mM	0.4226 mL	2.1130 mL	4.2260 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.