PI3Kα-IN-9 (compound 27) is a selective, oral, long-acting PI3Kα inhibitor (PI3Kα inhibitor) with IC50s of 4.4, 128, 146 and 153 nM for PI3Kα, PI3Kγ, PI3Kδ and PI3Kβ respectively. PI3Kα-IN-9 has antiproliferation activity and causes apoptosis. PI3Kα-IN-9 could be used in cancer-related research.

Physicochemical Properties

Molecular Formula	C18H21N7O3
Molecular Weight	383.404442548752
Exact Mass	383.17
CAS #	2715287-67-3
PubChem CID	164886635
Appearance	White to off-white solid powder
LogP	1.3
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	3
Heavy Atom Count	28
Complexity	491
Defined Atom Stereocenter Count	0
SMILES	O1C2=CC=C(C3=NC(N4CCOCC4)=NC(N4CCOCC4)=N3)C=C2N=C1N
InChi Key	LOQNSAZUXOBMAX-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H21N7O3/c19-16-20-13-11-12(1-2-14(13)28-16)15-21-17(24-3-7-26-8-4-24)23-18(22-15)25-5-9-27-10-6-25/h1-2,11H,3-10H2,(H2,19,20)
Chemical Name	5-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)-1,3-benzoxazol-2-amine
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	PI3Kα-IN-9 (compound 27) (0-8 μM; 72 hours; cancer cell line) inhibits proliferation and triggers apoptosis [1]. Compound 27 (PI3Kα-IN-9) (0-8 μM; MGC-803 cells) suppresses the expression of p-AKT, p-P70S6 K, PI3K downstream proteins, and PI3Kα protein [1]. Finding the viability of cells[1]
ln Vivo	Compound 27, also known as PI3Kα-IN-9, has a high degree of bioavailability (130%) and good stability (T1/2>10 hours) when administered orally and intravenously to male Sprague-Dawley rats (1–10 mg/kg) for a 24-hour period[1]. Compound 27, orally administered at a dose of 30 mg/kg every day for three weeks to male BALB/c nude mice, possesses low cytotoxicity and antitumor activity [1].
Cell Assay	Cell viability detection[1] Cell Types: MGC-803 (gastric cancer), SKOV-3 (ovarian cancer), PC-3 (prostate cancer), MCF-7 (breast cancer), MDA-MB-231 (triple negative) breast cancer), HepG2 (liver cancer), RPMI8226 (multiple myeloma), K562 (chronic myeloid leukemia), U251 (glioma), and MOLT-4 (acute lymphoblastic leukemia) cell lines Tested Concentrations: 0-2 μM for Incubation Duration: 72 hrs (hours) Experimental Results: Inhibited the growth of various cancer cells with IC50 values ranging from 0.43 to 1.33 μM. Apoptosis analysis [1] Cell Types: MGC-803 Cell Tested Concentrations: 0, 2, 4 and 8 μM Incubation Duration: 36 hrs (hours) Experimental Results: The percentage of apoptotic cells increased from 12.07% to 61.69% in a dose-dependent manner.
Animal Protocol	Animal/Disease Models: Male BALB/c nude mice [1] Doses: 30 mg/kg Route of Administration: Oral administration; one time/day for 3 weeks Experimental Results: Inhibition of tumor growth, tumor The growth inhibition (TGI) rate was 41.5%.
References	[1]. Discovery of Novel Phosphoinositide-3-Kinase α Inhibitors with High Selectivity, Excellent Bioavailability, and Long-Acting Efficacy for Gastric Cancer. J Med Chem. 2022 Jul 14.

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	2.6082 mL	13.0412 mL	26.0824 mL
	5 mM	0.5216 mL	2.6082 mL	5.2165 mL
	10 mM	0.2608 mL	1.3041 mL	2.6082 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.