SB02024 is a potent and orally active VPS34 inhibitor. SB02024 inhibits Vps34 kinase activity. SB02024 induces CCL5 and CXCL10 via STAT1/IRF7. SB02024 exhibits anticancer activity.

Physicochemical Properties

Molecular Formula	C16H22F3N3O2
Molecular Weight	345.36
Exact Mass	345.166
CAS #	2126737-28-6
PubChem CID	141711558
Appearance	White to off-white solid powder
LogP	2.5
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	2
Heavy Atom Count	24
Complexity	559
Defined Atom Stereocenter Count	2
SMILES	C[C@@H]1COCCN1C2=CC(=O)NC(=C2)N3CCCC[C@@H]3C(F)(F)F
InChi Key	IARAUFAUVKBTEM-DGCLKSJQSA-N
InChi Code	InChI=1S/C16H22F3N3O2/c1-11-10-24-7-6-21(11)12-8-14(20-15(23)9-12)22-5-3-2-4-13(22)16(17,18)19/h8-9,11,13H,2-7,10H2,1H3,(H,20,23)/t11-,13-/m1/s1
Chemical Name	4-[(3R)-3-methylmorpholin-4-yl]-6-[(2R)-2-(trifluoromethyl)piperidin-1-yl]-1H-pyridin-2-one
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	Vps34 STAT1
ln Vitro	SB02024 (5 μM, 48 hours) induces CCL5 and CXCL10 via STAT1/IRF7 in B16-F10 and CT26 tumor cells[1].
ln Vivo	SB02024 (20 mg/kg, oral gavage) reduces tumor growth and enhances the efficacy of anti-PD-L1/PD-1[1]. SB02024 increases the levels of CCL5 and CXCL10 in the plasma of B16-F10 and CT26 tumor-bearing mice, but does not increase the levels of CCL5 or CXCL10 in the blood of non-tumor-bearing mice[1].
Cell Assay	Western Blot Analysis[1] Cell Types: B16-F10 and CT26 tumor Tested Concentrations: 5 μM Incubation Duration: 48 h Experimental Results: Significantly up-regulates both Ccl5/Rantes and Cxcl10/IP10 mRNA and their corresponding secreted protein levels in YUMM cells, B16-F10 and CT26 tumor cells. Showed an induction of phospho-signal transducer and activator of transcription 1 (pSTAT1) and increased protein and mRNA expression of STAT1, IRF1 and IRF7.
Animal Protocol	Animal/Disease Models:C57BL/6, BALB/C, immunodeficient NSG mice (7 weeks old)[1] Doses: 20 mg/kg Route of Administration: Oral gavage Experimental Results: Decreased the tumor growth and weight of B16-F10 and CT26 and prolonged the survival of tumor-bearing mice.
References	[1]. Inhibition of Vps34 reprograms cold into hot inflamed tumors and improves anti-PD-1/PD-L1 immunotherapy. Sci Adv. 2020 Apr 29;6(18):eaax7881. [2]. Combining VPS34 inhibitors with STING agonists enhances type I interferon signaling and anti-tumor efficacy. Mol Oncol. 2024 Mar 20. [3]. Biomarker. Patent WO2020008046 A1.

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	2.8955 mL	14.4776 mL	28.9553 mL
	5 mM	0.5791 mL	2.8955 mL	5.7911 mL
	10 mM	0.2896 mL	1.4478 mL	2.8955 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.