AKT-IN-1 is an allosteric AKT inhibitor (antagonist) with IC50 of 1.042 μM.

Physicochemical Properties

Molecular Formula	C22H21N3O
Molecular Weight	343.43
Exact Mass	343.168
CAS #	1357158-81-6
PubChem CID	56953649
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Boiling Point	496.4±45.0 °C at 760 mmHg
Flash Point	254.0±28.7 °C
Vapour Pressure	0.0±1.3 mmHg at 25°C
Index of Refraction	1.643
LogP	2.87
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	26
Complexity	490
Defined Atom Stereocenter Count	0
InChi Key	GIRZDHCBMNHMEH-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H21N3O/c23-21(26)17-13-19(15-5-2-1-3-6-15)20(25-14-17)16-7-9-18(10-8-16)22(24)11-4-12-22/h1-3,5-10,13-14H,4,11-12,24H2,(H2,23,26)
Chemical Name	6-[4-(1-aminocyclobutyl)phenyl]-5-phenylpyridine-3-carboxamide
Synonyms	AZD-26 AZD26 AZD 26
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	AKT-IN-1 has an IC50 of 0.422 and 0.322 μM, respectively, which allows it to effectively block the phosphorylation of AKT Thr308 and Ser473 sites in cells. Because ribosomal protein S6 is a downstream effector of the PI3K-AKT pathway, AKT-IN-1 prevents it from becoming phosphorylated. PRAS40 phosphorylation is efficiently inhibited by AKT-IN-1 [1].
ln Vivo	Compound 26 (AKT-IN-1) in vivo effects were evaluated by assessing the compound's pharmacodynamic efficacy in the BT474c breast cancer xenograft model. AKT-IN-1 efficiently prevented the phosphorylation of AKT (Ser473) and its downstream substrate GSK3β after acute dosages of 100 and 200 mg/kg. Its effectiveness was in line with its pharmacokinetic properties. By assessing the impact on the growth of tumor cell xenografts, the in vivo activity of AKT-IN-1 was further described. AKT-IN-1 (100 and 200 mg/kg) given orally, continuously, and daily to nude mice containing BT474c mammary adenocarcinoma xenografts suppresses tumor growth in a dose-dependent manner. At a daily dosage of 200 mg/kg, AKT-IN-1 significantly inhibits the growth of tumors [1].
References	[1]. Diverse heterocyclic scaffolds as allosteric inhibitors of AKT. J Med Chem. 2012 Feb 9;55(3):1261-73.

Solubility Data

Solubility (In Vitro)

DMSO : ~75 mg/mL (~218.39 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.28 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 (7.28 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 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 (7.28 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	2.9118 mL	14.5590 mL	29.1180 mL
	5 mM	0.5824 mL	2.9118 mL	5.8236 mL
	10 mM	0.2912 mL	1.4559 mL	2.9118 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.