PKI-179 HCl is a potent and orally bioactive dual PI3K/mTOR inhibitor (antagonist) with IC50s of 8 nM and 24 nM for PI3K-α, PI3K-β, PI3K-γ, PI3K-δ and mTOR, respectively. 74 nM, 77 nM and 0.42 nM. PKI-179 HCl also showed activity against E545K and H1047R with IC50s of 14 nM and 11 nM, respectively. PKI-179 HCl displays anticancer effect in vivo.

Physicochemical Properties

Molecular Formula	C25H29CLN8O3
Molecular Weight	525.002563238144
Exact Mass	524.205
CAS #	1463510-35-1
Related CAS #	PKI-179;1197160-28-3
PubChem CID	137699924
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	5
Heavy Atom Count	37
Complexity	714
Defined Atom Stereocenter Count	0
SMILES	N(C1C=CC(C2N=C(N3CCOCC3)N=C(N3C4COCC3CC4)N=2)=CC=1)C(=O)NC1=CC=NC=C1.Cl
InChi Key	JNMURGIZAFELTR-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H28N8O3.ClH/c34-25(28-19-7-9-26-10-8-19)27-18-3-1-17(2-4-18)22-29-23(32-11-13-35-14-12-32)31-24(30-22)33-20-5-6-21(33)16-36-15-20;/h1-4,7-10,20-21H,5-6,11-16H2,(H2,26,27,28,34);1H
Chemical Name	1-[4-[4-morpholin-4-yl-6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1,3,5-triazin-2-yl]phenyl]-3-pyridin-4-ylurea;hydrochloride
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: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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	mTOR 0.42 nM (IC50) PI3Kα 8 nM (IC50) PI3Kβ 24 nM (IC50) PI3Kγ 74 nM (IC50) PI3Kδ 77 nM (IC50) E545K 14 nM (IC50) H1047R 77 nM (IC50)
ln Vitro	PKI-179 reduces the growth of cells, exhibiting IC50 values for MDA361 and PC3 cells of 22 nM and 29 nM, respectively[1]. At dosages up to >30 μM, PKI-179 exhibits inhibitory activity against a panel of 361 different kinases, hERG, and cytochrome P450 (CYP) isoforms; nevertheless, it does exhibit activity for CYP2C8 (IC50=3 μM)[1].
ln Vivo	In nude mice bearing MDA-361 human breast cancer tumors, PKI-179 (5-50 mg/kg; po once daily for 40 days) reduces the tumor growth and is well tolerated[1]. Good suppression of PI3K signaling is observed in nude mice containing MDA361 tumor xenografts when PKI-179 (50 mg/kg; po) is administered[1]. PKI-179 has a high half-life (>60 min) and good oral bioavailability (98% in naked mouse, 46% in rat, 38% in monkey, and 61% in dog)[1].
Animal Protocol	Animal/Disease Models: Nude mice bearing MDA-361 human breast cancer tumors[1] Doses: 5, 10, 25, 50 mg/kg Route of Administration: Ip every 3 days for 4 weeks Experimental Results: demonstrated pronounced tumor growth arrest when dosed above 10 mg/kg. No significant weight loss of tested animals was observed for all different dosages.
References	[1]. PKI-179: an orally efficacious dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor. Bioorg Med Chem Lett. 2010 Oct 1;20(19):5869-73. [2]. Rehan M. A structural insight into the inhibitory mechanism of an orally active PI3K/mTOR dual inhibitor, PKI-179 using computational approaches. J Mol Graph Model. 2015 Nov;62:226-234.

Solubility Data

Solubility (In Vitro)

DMSO: 20 mg/mL (38.10 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (2.38 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 12.5 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 2: ≥ 1.25 mg/mL (2.38 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 12.5 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	1.9048 mL	9.5238 mL	19.0476 mL
	5 mM	0.3810 mL	1.9048 mL	3.8095 mL
	10 mM	0.1905 mL	0.9524 mL	1.9048 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.