M77976 is a specific, ATP-competitive inhibitor of pyruvate dehydrogenase kinase PDK4 with IC50 of 648 μM. M77976 has potential usefulness in obesity and diabetes research.

Physicochemical Properties

Molecular Formula	C17H16N2O3
Molecular Weight	296.321
Exact Mass	296.116
CAS #	394237-61-7
PubChem CID	764764
Appearance	White to off-white solid powder
LogP	3.2
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Heavy Atom Count	22
Complexity	360
Defined Atom Stereocenter Count	0
SMILES	COC1=CC=C(C2=C(C)NN=C2C2=CC=C(O)C=C2O)C=C1
InChi Key	GSBFARPNIZUMHA-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H16N2O3/c1-10-16(11-3-6-13(22-2)7-4-11)17(19-18-10)14-8-5-12(20)9-15(14)21/h3-9,20-21H,1-2H3,(H,18,19)
Chemical Name	4-[4-(4-methoxyphenyl)-5-methyl-1H-pyrazol-3-yl]benzene-1,3-diol
Synonyms	M 77976; M-77976; M77976
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	Complete disruption of the ATP cover is the outcome of local conformational alterations brought about by M77976's attachment to PDK4's ATP-binding pocket [1]. M77976 interacts hydrophobically with PDK4 side chains Asn258, Ala262, Val298, Leu306, and Thr358 [1].
References	[1]. Inhibitor-bound structures of human pyruvate dehydrogenase kinase 4. Acta Crystallogr D Biol Crystallogr. 2011 Sep;67(Pt 9):763-73.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~843.68 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (7.02 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 20.8 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: ≥ 2.08 mg/mL (7.02 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 20.8 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: ≥ 2.08 mg/mL (7.02 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 20.8 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	3.3747 mL	16.8737 mL	33.7473 mL
	5 mM	0.6749 mL	3.3747 mL	6.7495 mL
	10 mM	0.3375 mL	1.6874 mL	3.3747 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.