JX06 is a potent, selective, covalent PDK inhibitor. JX06 inhibits PDK1, PDK2 and PDK3 with IC50s of 49 nM, 101 nM and 313 nM respectively. JX06 inhibits PDK1 activity by covalently binding to cysteine residues in an irreversible manner. JX06 has anti-tumor effects.

Physicochemical Properties

Molecular Formula	C10H16N2O2S4
Molecular Weight	324.49
Exact Mass	324.009
Elemental Analysis	C, 37.02; H, 4.97; N, 8.63; O, 9.86; S, 39.52
CAS #	729-46-4
Related CAS #	729-46-4
PubChem CID	12892
Appearance	White to off-white solid powder
Density	1.463g/cm3
Boiling Point	466.3ºC at 760 mmHg
Flash Point	235.8ºC
Index of Refraction	1.69
LogP	1.477
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	3
Heavy Atom Count	18
Complexity	274
Defined Atom Stereocenter Count	0
SMILES	C1COCCN1C(=S)SSC(=S)N2CCOCC2
InChi Key	KKVYOWPPMNSLCP-UHFFFAOYSA-N
InChi Code	InChI=1S/C10H16N2O2S4/c15-9(11-1-5-13-6-2-11)17-18-10(16)12-3-7-14-8-4-12/h1-8H2
Chemical Name	morpholine-4-carbothioylsulfanyl morpholine-4-carbodithioate
Synonyms	JX06 JX 06 JX-06
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 (IC50 = 49 nM); PDK2 (IC50= 101 nM); PDK3 (IC50= 313 nM)
ln Vitro	JX06 barely shows inhibitory activity against PDK4 at a concentration of 10 μM[1]. JX06 (1-10 μM; 48 hours) induces cell apoptosis in cancer cells with high ECAR/OCR[1].JX06(0-0.6 μM; 72 hours) inhibits the growth of A549 cells in a dose-dependent manner[1]. JX06(0.1-10 μM; 6-24 hours) inhibits PDHA1 phosphorylation in A549 cells in a time- and dose-dependent manner.[1] JX06 (1–10 μM) increases intracellular ATP levels and glucose uptake while decreasing aerobic glycolysis as measured by lactate production in A549 cells[1]. JX06 (1-10 μM; 24 hours) induces ROS generation in cancer cells with high extracellular acidification rate (ECAR)/ oxygen consumption rate (OCR) [1].
ln Vivo	JX06 (40-80 mg/kg; i.p. for 21 days) inhibits tumor growth in vivo[1].
Animal Protocol	A549 subcutaneous xenograft mice[1] 40, 80 mg/kg I.p. injections for 21 days
References	[1]. JX06 Selectively Inhibits Pyruvate Dehydrogenase Kinase PDK1 by a Covalent Cysteine Modification. Cancer Res. 2015 Nov 15; 75(22): 4923-36.

Solubility Data

Solubility (In Vitro)

DMSO: 50~65 mg/mL (154.1~200.3 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.70 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 (7.70 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (7.70 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	3.0818 mL	15.4088 mL	30.8176 mL
	5 mM	0.6164 mL	3.0818 mL	6.1635 mL
	10 mM	0.3082 mL	1.5409 mL	3.0818 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.