JX 06

Names

[ CAS No. ]:
729-46-4

[ Name ]:
JX 06

[Synonym ]:
DISULFIDE,BIS(MORPHOLINOTHIOCARBONYL)
Dimorpholinothiuramdisulfid
Disulfide,bis(4-morpholinylthioxomethyl)
Bis(morpholinothiocarbonyl) disulfide
Morpholine,4,4'-(dithiodicarbonothioyl)bis
Dimorpholinethiuram disulfide
Bis(4-morpholinothiocarbonyl) disulfide
N,N'-morpholinothiuram disulfide
4-Morpholinethiocarbonyl disulfide
bis(morpholinothiocarbonyl) disulphide
4,4'-(Dithiodicarbonothioyl)dimorpholine

Biological Activity

[Description]:

JX06 is a potent, selective and covalent inhibitor of PDK. JX06 inhibits PDK1, PDK2 and PDK3 with the IC50s of 49 nM, 101 nM, and 313 nM, respectively. JX06 inhibits PDK1 activity via covalently binding to a cysteine residue in an irreversible manner. JX06 shows significant antitumor activity[1].

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> PDHK

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

[Target]

IC50: 49 nM (PDK1), 101 nM (PDK2), 313 nM (PDK3)[1]

[In 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) dose-dependently suppresses the growth of A549 cells[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 glucose uptake and intracellular ATP level and reduces aerobic glycolysis determined by the 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]. Apoptosis Analysis[1] Cell Line: A549, EBC-1, HT-29 and H460 cells Concentration: 0, 1, 3, 10 μM Incubation Time: 48 hours Result: Induces cell apoptosis in A549 and EBC-1 cells. Cell Viability Assay[1] Cell Line: A549 cells Concentration: 0, 0.2, 0.4, 0.6 μM Incubation Time: 72 hours Result: Inhibits the viability of A549 cells in a dose dependent manner. Western Blot Analysis[1] Cell Line: A549 cells Concentration: 0, 0.1, 0.3, 1, 3, 10 μM Incubation Time: 0, 6, 12, 24 hours Result: Decreased PDHA1 phosphorylation at both serine 293 and serine 232 (S293 and S232) in a time- and dose-dependent manner.

[In Vivo]

JX06 (40-80 mg/kg; i.p. for 21 days) inhibits tumor growth in vivo[1]. Animal Model: A549 subcutaneous xenograft mice[1] Dosage: 40, 80 mg/kg Administration: I.p. injections for 21 days Result: Reduced tumor weights and 67.5% tumor volume at the dose of 80 mg/kg compared with the vehicle control. Well tolerated at the administration dose.

[References]

[1]. Wenyi S, et, al. JX06 Selectively Inhibits Pyruvate Dehydrogenase Kinase PDK1 by a Covalent Cysteine Modification. Cancer Res. 2015 Nov 15; 75(22): 4923-36.

Chemical & Physical Properties

[ Density]:
1.463g/cm3

[ Boiling Point ]:
466.3ºC at 760 mmHg

[ Molecular Formula ]:
C₁₀H₁₆N₂O₂S₄

[ Molecular Weight ]:
324.50600

[ Flash Point ]:
235.8ºC

[ Exact Mass ]:
324.00900

[ PSA ]:
139.72000

[ LogP ]:
1.47780

[ Index of Refraction ]:
1.69

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: JO1530000

CHEMICAL NAME :: Disulfide, bis(morpholinothiocarbonyl)

CAS REGISTRY NUMBER :: 729-46-4

BEILSTEIN REFERENCE NO. :: 0276307

LAST UPDATED :: 199710

DATA ITEMS CITED :: 3

MOLECULAR FORMULA :: C10-H16-N2-O2-S4

MOLECULAR WEIGHT :: 324.52

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 3250 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 112,36,1957

Safety Information

[ Hazard Codes ]:
Xn