PI3Kδ-IN-8 is a specific and orally bioactive PI3Kδ inhibitor (antagonist) with IC50 of 3.3 nM. PI3Kδ-IN-8 is more selective for PI3Kδ than PI3Kα, PI3Kβ, and PI3Kγ (IC50=377.2, 241.6, 17.9 nM). PI3Kδ-IN-8 has anticancer effect.

Physicochemical Properties

Molecular Formula	C28H21F2N7O
Molecular Weight	509.51
Exact Mass	509.177
CAS #	2101518-75-4
PubChem CID	129262522
Appearance	Typically exists as solid at room temperature
LogP	3.7
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	5
Heavy Atom Count	38
Complexity	1110
Defined Atom Stereocenter Count	1
SMILES	C[C@@H](C1=C(C(=O)N2C=C(C=CC2=C1C3=CC=C(C=C3)F)F)C4=CC=CC=C4)NC5=NC(=NC(=C5C#N)N)N
InChi Key	YPUUKLQYBLWUEU-HNNXBMFYSA-N
InChi Code	InChI=1S/C28H21F2N7O/c1-15(34-26-20(13-31)25(32)35-28(33)36-26)22-23(17-7-9-18(29)10-8-17)21-12-11-19(30)14-37(21)27(38)24(22)16-5-3-2-4-6-16/h2-12,14-15H,1H3,(H5,32,33,34,35,36)/t15-/m0/s1
Chemical Name	2,4-diamino-6-[[(1S)-1-[7-fluoro-1-(4-fluorophenyl)-4-oxo-3-phenylquinolizin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile
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	PI3Kδ 3.3 nM (IC50) PI3Kγ 17.9 nM (IC50) PI3Kβ 241.6 nM (IC50) PI3Kα 377.2 nM (IC50)
ln Vitro	PI3Kδ-IN-8 (compound 34) (0.1 nM-10 μM; 96 h), exhibits remarkable efficacy against representative DLBCL cell lines, whether they belong to the ABC subtype (OCI-Ly10 and TMD-8) or GCB (SUDHL-6)[1]. With an IC50 of 9.5 nM, PI3Kδ-IN-8 (1 h) suppresses the PI3K-induced AKT phosphorylation in anti-IgM activated Raji cells[1].
ln Vivo	In mice, PI3Kδ-IN-8 (1-30 mg/kg; po once daily for 24 d) significantly and dose-dependently decreases tumor weight and volume[1]. In mice, PI3Kδ-IN-8 (1 mg/kg; iv) exhibits a low clearance (5.6 mL/min/kg), an acceptable half-life (1 h), and a Cmax (2.3 μM)[1]. AUClast (22 μM·h), Cmax (7.5 μM), and moderate oral bioavailability (39%), are demonstrated by PI3Kδ-IN-8 (10 mg/kg; po) in mice[1].
Cell Assay	Cell Viability Assay[1] Cell Types: SUDHL-6, OCI-Ly10, and TMD-8 cell lines Tested Tested Concentrations: 0.1, 1, 10, 100, 1000, 10000 nM Incubation Duration: 96 hrs (hours) Experimental Results: Inhibited the viability of SUDHL-6, OCI-Ly10, and TMD-8 cells, with IC50s of <0.1 nM, <1 nM, and <0.1 nM, respectively.
Animal Protocol	Animal/Disease Models: Female NOD SCID (severe combined immunodeficient) mouse were injected OCI-Ly10 cells[1] Doses: 1, 3, 10, 30 mg/kg Route of Administration: Po one time/day for 24 days Experimental Results: decreased the tumor volume, with an ED50 of 6.47 mg/kg. Tumor growth inhibition of 81.95% was seen with a highly significant reduction in both tumor volume and tumor weight. Animal/Disease Models: Male BALB/c mice[1] Doses: 1 mg/kg for iv; 10 mg/kg for po (pharmacokinetic/PK Analysis) Route of Administration: intravenous (iv) administration and oral administration Experimental Results: Iv: t1/2=1 h, Cmax =2.3 μM, CL=5.6 mL/min/kg. Po: F=39%, Cmax=7.5 μM, AUClast=22μM·h.
References	[1]. Discovery of a Potent and Selective PI3Kδ Inhibitor (S)-2,4-Diamino-6-((1-(7-fluoro-1-(4-fluorophenyl)-4-oxo-3-phenyl-4H-quinolizin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile with Improved Pharmacokinetic Profile and Superior Efficacy i.

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	1.9627 mL	9.8134 mL	19.6267 mL
	5 mM	0.3925 mL	1.9627 mL	3.9253 mL
	10 mM	0.1963 mL	0.9813 mL	1.9627 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.