PS210 (PS-210) is a novel and potent activator (in vitro) or inhibitor (in cells) of protein kinase PDK1 with anticancer activity. It does not affect any of the 121 kinases, such as S6K, PKB/Akt, or GSK3, and instead targets the PDK1-interacting fragment (PIF)-binding pocket. PS210 is a powerful PDK1 activator in vitro, and the crystal structure of the PDK1-ATP-PS210 complex demonstrates that PS210 stimulates the kinase domain's closure. While not affecting PKB/Akt, the prodrug of PS210 (PS423) functions in cells as a substrate-selective inhibitor of PDK1, preventing the phosphorylation and activation of S6K, which requires docking to the PIF-pocket.

Physicochemical Properties

Molecular Formula	C19H15F3O5
Molecular Weight	380.314616441727
Exact Mass	380.087
Elemental Analysis	C, 60.00; H, 3.98; F, 14.99; O, 21.03
CAS #	1221962-86-2
Related CAS #	(R)-PS210;1410101-89-1
PubChem CID	66760004
Appearance	White to off-white solid powder
LogP	3.5
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	7
Heavy Atom Count	27
Complexity	532
Defined Atom Stereocenter Count	0
InChi Key	MLJPLHGJBUWCBA-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H15F3O5/c20-19(21,22)13-8-6-12(7-9-13)15(23)10-14(11-4-2-1-3-5-11)16(17(24)25)18(26)27/h1-9,14,16H,10H2,(H,24,25)(H,26,27)
Chemical Name	2-(3-Oxo-1-phenyl-3-(4-(trifluoromethyl)phenyl)propyl)malonic acid
Synonyms	PS 210; PS-210; PS210
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	PDK1 (Kd = 3 μM)
ln Vitro	When PS210 causes PDK1 to stabilize at a specific temperature, PS210 stabilized the residue Arg131, which is located across from helix a-B at the opposite end of helix a-C. As a result, it appears that the residues constituting the phosphate-binding site are a fixed point that permits the relative movement of the helices during PDK1 activation[1].
References	[1]. Substrate-selective inhibition of protein kinase PDK1 by small compounds that bind to the PIF-pocket allosteric docking site. [2]. A small-molecule mimic of a peptide docking motif inhibits the protein kinase PDK1. Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):18590-5.

Solubility Data

Solubility (In Vitro)

DMSO: 76~100 mg/mL (199.8~262.9 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.57 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 (6.57 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 (6.57 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6294 mL	13.1472 mL	26.2943 mL
	5 mM	0.5259 mL	2.6294 mL	5.2589 mL
	10 mM	0.2629 mL	1.3147 mL	2.6294 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.