PS10 is a novel, potent and ATP-competitive broad spectrum (a wide range) PDK inhibitor that can suppress all PDK isoforms with IC50s of 0.8 μM, 0.76 μM, 2.1 μM and 21.3 μM for PDK2, PDK4, PDK1 and PDK3, respectively. . PS10 has a higher affinity for PDK2 (Kd= 239 nM) than for Hsp90 (Kd= 47 μM). PS10 improves glucose tolerance and stimulates myocardial carbohydrate oxidation in diet-induced obesity. PS10 may be used for studying diabetic cardiomyopathy.

Physicochemical Properties

Molecular Formula	C14H13NO6S
Molecular Weight	323.32112288475
Exact Mass	323.046
CAS #	1564265-82-2
PubChem CID	72376512
Appearance	Light yellow to khaki solid powder
LogP	1.3
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	2
Heavy Atom Count	22
Complexity	506
Defined Atom Stereocenter Count	0
SMILES	S(C1C=CC(=CC=1O)O)(N1CC2C=C(C=C(C=2C1)O)O)(=O)=O
InChi Key	SVUZJWAAXPEMKJ-UHFFFAOYSA-N
InChi Code	InChI=1S/C14H13NO6S/c16-9-1-2-14(13(19)4-9)22(20,21)15-6-8-3-10(17)5-12(18)11(8)7-15/h1-5,16-19H,6-7H2
Chemical Name	2-(2,4-dihydroxyphenyl)sulfonyl-1,3-dihydroisoindole-4,6-diol
Synonyms	PS-10; PS 10
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

ln Vitro	Compared to Hsp90 (Kd= 47,000 nM), PS10 exhibits a higher affinity for PDK2 (Kd= 239 nM) [1]. With an IC50 value of 284 μM for growth inhibition in HeLa cells, PS10 is less toxic and less powerful than cycloheximide [1].
ln Vivo	Treatment with PS10 (ip; 70 mg/kg; single dosage) boosted PDC activity in the liver and heart by 23 and 11 times, respectively. Concurrently, the kidney's PDC activity increased by 1.4 times in comparison to the vehicle group [1]. The PDC activity profiles and phospho-E1α subunit levels were similar to single doses after three days of PS10 (ip; 70 mg/kg). Remarkably, the elevation of PDK activity in the heart was decreased after three days of therapy [1]. After receiving PS10 (ip; 70 mg/kg) for four weeks, mice were tested for glucose tolerance. The plasma glucose levels in the vehicle-treated controls peaked at 482 mg/dl at 30 minutes after being challenged with 1.5 g/kg glucose, and then dropped to 210 mg/dl after 120 minutes. Compared to animals treated with a vehicle, the glucose levels in PS10-treated DIO mice were lower at 0 min, measuring 168 mg/dl. After 30 min, the levels rose to 312 mg/dl, and after 120 min, they were back to 163 mg/dl. [1]. PDC flow is stimulated by both PS10 (ip; 70 mg/kg) and DCA (measured by the emergence of hyperpolarizing [13C]bicarbonate). It has a comparable reaction to glucose, and a glucose stimulus can reinstate PDC activity in DIO mice's hearts [2].
Animal Protocol	Animal/Disease Models: 6 to 8 weeks old C57BL/6J male mice [2] Doses: 70 mg/kg/day Route of Administration: intraperitoneal (ip) injection Experimental Results: Improved glucose tolerance in intact animals.
References	[1]. Structure-guided development of specific pyruvate dehydrogenase kinase inhibitors targeting the ATP-binding pocket.J Biol Chem. 2014 Feb 14;289(7):4432-43. [2]. A novel inhibitor of pyruvate dehydrogenase kinase stimulates myocardial carbohydrate oxidation in diet-induced obesity.J Biol Chem. 2018 Jun 22;293(25):9604-9613.

Solubility Data

Solubility (In Vitro)

DMSO : ~62.5 mg/mL (~193.31 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 6.25 mg/mL (19.33 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 62.5 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: ≥ 6.25 mg/mL (19.33 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 62.5 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.0929 mL	15.4646 mL	30.9291 mL
	5 mM	0.6186 mL	3.0929 mL	6.1858 mL
	10 mM	0.3093 mL	1.5465 mL	3.0929 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.