PI3K-IN-22 is a PI3Kα/mTOR dual kinase inhibitor. The IC50s values of PI3K-IN-22 for PI3Kα and mTOR are 0.9 and 0.6 nM respectively. PI3K-IN-22 could be used in cancer research.

Physicochemical Properties

Molecular Formula	C31H35F3N8O3
Molecular Weight	624.66
Exact Mass	624.278
CAS #	1202884-94-3
PubChem CID	44599690
Appearance	White to light yellow solid powder
Density	1.4±0.1 g/cm3
Index of Refraction	1.625
LogP	2.42
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	9
Heavy Atom Count	45
Complexity	968
Defined Atom Stereocenter Count	0
SMILES	CN(C)CCN(C)C(=O)C1=CC=C(C=C1)NC(=O)NC2=CC=C(C=C2)C3=NC(=C4C=CN(CC(F)(F)F)C4=N3)N5CCOCC5
InChi Key	GMASZVAHNYVURN-UHFFFAOYSA-N
InChi Code	InChI=1S/C31H35F3N8O3/c1-39(2)14-15-40(3)29(43)22-6-10-24(11-7-22)36-30(44)35-23-8-4-21(5-9-23)26-37-27(41-16-18-45-19-17-41)25-12-13-42(28(25)38-26)20-31(32,33)34/h4-13H,14-20H2,1-3H3,(H2,35,36,44)
Chemical Name	N-[2-(dimethylamino)ethyl]-N-methyl-4-[[4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)pyrrolo[2,3-d]pyrimidin-2-yl]phenyl]carbamoylamino]benzamide
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

Targets	PI3Kα 0.9 nM (IC50) mTOR 0.6 nM (IC50)
ln Vitro	PC3 and MDA-361 cell growth is inhibited by PI3K-IN-22 (compound 46), with IC50s of less than 3.0 and 13.0 nM, respectively[1].
ln Vivo	Biomarker studies have shown that PI3K-IN-22 (25 mg/kg; iv) reduces phosphorylation of Akt T308, Akt S473, and S6K in MDA361 breast tumor cells for up to 8 hours in MDA361 tumor bearing nude mice[1]. In an MDA361 tumor xenograft nude mouse model, PI3K-IN- 22 (50, 25, 10 mg/kg; iv; once daily for five days weekly; two cycles) exhibits good anticancer efficacy[1]. The blood concentration of PI3K-IN-22 (25 mg/kg; IV; single dosage) is 1731 ng/mL at 8 hours[1].
Animal Protocol	Animal/Disease Models: MDA361 tumor xenograft nude mice model[1] Doses: 50, 25, 10 mg/kg Route of Administration: iv, one time/day for 5 days weekly (2 rounds) Experimental Results: demonstrated significant tumor regression in 50 mg/kg and no tumor regrowth until day 32. demonstrated tumor growth inhibition in 25 and 10 mg/kg.
References	[1]. Synthesis and SAR of novel 4-morpholinopyrrolopyrimidine derivatives as potent phosphatidylinositol 3-kinase inhibitors. J Med Chem. 2010 Apr 22;53(8):3169-82.
Additional Infomation	CAY10626 is a member of ureas.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.6009 mL	8.0044 mL	16.0087 mL
	5 mM	0.3202 mL	1.6009 mL	3.2017 mL
	10 mM	0.1601 mL	0.8004 mL	1.6009 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.