MT 63-78 is a potent direct AMPK activator with EC50 of 25 μM. M 63-78 also induces mitotic arrest and apoptosis. MT 63-78 blocks prostate cancer growth by inhibiting adipogenesis and mTORC1 pathways. MT 63-78 Has potential anticancer/anti-tumor effects.

Physicochemical Properties

Molecular Formula	C21H14N2O2
Molecular Weight	326.348064899445
Exact Mass	326.105
CAS #	1179347-65-9
PubChem CID	59145386
Appearance	Light yellow to brown solid powder
LogP	4.3
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	2
Heavy Atom Count	25
Complexity	497
Defined Atom Stereocenter Count	0
SMILES	OC1C=CC=C(C=1C1C=CC(=CC=1)C1C=CC2=C(C(C#N)=CN2)C=1)O
InChi Key	IGSYZPLXAFVMKY-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H14N2O2/c22-11-16-12-23-18-9-8-15(10-17(16)18)13-4-6-14(7-5-13)21-19(24)2-1-3-20(21)25/h1-10,12,23-25H
Chemical Name	5-[4-(2,6-dihydroxyphenyl)phenyl]-1H-indole-3-carbonitrile
Synonyms	MT63-78; MT63 78; MT6378
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 Note: This product requires protection from light (avoid light exposure) during transportation and storage.
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	LNCaP and PC3 cells treated with MT 63-78 (0-50 μM; 4 days) exhibit a dose-dependent decrease in cell number along with activation of AMPK signaling [1]. The G2/M population is significantly enriched when LNCaP and CRPC cells are treated with MT 63-78 (25 μM; 24 hours) [1]. Pro-apoptotic BH3 protein Puma accumulates in conjunction with a decrease in anti-apoptotic Mcl-1 in LNCaP, PC3, C4-4, C4-2B, CL1, and 22RV1 cells treated with MT 63-78 (0-50 μM; 24 hr) [1]. Following treatment with MT 63-78 (0-50 μM; 30 min) in LNCaP and PC3 cells, phosphorylation of two important AMPK targets (raptor on Ser792 and acetyl-CoA carboxylase (ACC) on Ser79) was observed in a dose-dependent manner. Furthermore, it raises Thr172's phosphorylation on the AMPK α subunit [1].
ln Vivo	In C57 BL/6 male mice, treatment with MT 63-78 (30 mg/kg; i.p.; daily; for 14 days) reduced tumor growth by 33% [1].
Cell Assay	Cell Viability Assay[1] Cell Types: LNCaP and PC3 Cell Tested Concentrations: 0 μM, 1 μM, 5 μM, 10 μM, 25 μM, 50 μM Incubation Duration: 4 days Experimental Results: A dose-dependent decrease in cell number was observed simultaneously Activation of AMPK signaling. Cell cycle analysis[1] Cell Types: LNCaP and CRPC Cell Tested Concentrations: 25 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced significant enrichment of G2/M population in androgen-sensitive and CRPC cell models. Apoptosis analysis[1] Cell Types: LNCaP, PC3, C4-4, C4-2B, CL1 and 22RV1 Cell Tested Concentrations: 0 μM, 10 μM, 25 μM, 50 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induction of anti-apoptosis The decrease in Mcl-1 was consistent with the accumulation of the pro-apoptotic BH3 protein Puma in all PCa cells. Western Blot Analysis[1] Cell Types: LNCaP and PC3 Cell Tested Concentrations: 0 μM, 0.25 μM, 0.5 μM, 1 μM, 5 μM, 25 μM, 50 μM Incubation Duration: 30 min Experimental Results: Observed a dose-dependent phosphorylation of the two major AMPK targets Acetyl-CoA Carboxylase (ACC) on Ser79 and of Raptor on Ser792. A corresponding increase in Thr172 phosphorylation on the AMPK α subunit was also observed.
Animal Protocol	Animal/Disease Models: C57 BL/6 male mice bearing LNCaP tumors [1] Doses: 30 mg/kg Route of Administration: intraperitoneal (ip) injection; daily; lasted for 14 days. Experimental Results: resulted in 33% inhibition of tumor growth.
References	[1]. A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis. EMBO Mol Med. 2014 Apr;6(4):519-38.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~383.02 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.37 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 (6.37 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.0642 mL	15.3210 mL	30.6419 mL
	5 mM	0.6128 mL	3.0642 mL	6.1284 mL
	10 mM	0.3064 mL	1.5321 mL	3.0642 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.