SAR405

Catalog No.S7682 Batch:S768205

Technical Data

Formula	C₁₉H₂₁ClF₃N₅O₂
Molecular Weight	443.85	CAS No.	1523406-39-4
Solubility (25°C)*	In vitro	DMSO	89 mg/mL (200.51 mM)
		Ethanol	29 mg/mL (65.33 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

SAR405 is a low-molecular-mass kinase inhibitor of PIK3C3/Vps34 (KD 1.5 nM) showing high selectivity and not be active up to 10 μM on class I and class II PI3Ks as well as on mTOR. SAR405 prevents autophagy and synergizes with MTOR (mechanistic target of rapamycin) inhibition in tumor cells.

Targets

Vps34 ^[1]

1.2 nM

In vitro

SAR405 is an inhibitor that was highly specific for Vps34 with regard to protein kinases and other phosphoinositide kinases. SAR405 has an IC50 of 1 nM in the phosphorylation of a PtdIns substrate by human recombinant Vps34 enzyme. This compound shows a binding equilibrium constant KD of 1.52 ± 0.77 nM (± s.d.) and a dissociation rate constant, k_off, of 3.03 ± 0.55 10⁻³/s, corresponding to a residence half-life, t_1/2, of 3.8 min. SAR405 does not affect the Akt phosphorylation at concentrations up to 10 μM in the PC3 cell line. SAR405 affects vesicle trafficking from late endosomes to lysosomes. It is also a potent autophagy inhibitor^[1].

In vivo

SAR405 is a first-in-class, selective, and ATP-competitive PI3K class III (PIK3C3) isoform Vps34 inhibitor.

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines GFP-LC3 HeLa cells Concentrations 1 μM Incubation Time 4 h Method GFP-LC3 HeLa cells are starved for 2 h in EBSS plus 10 μM Vps34 compound or DMSO. For mTOR inhibitor, GFP-LC3 H1299 cells are treated with 1 μM AZD8055 for 4 h in fed conditions. Cells are then fixed with 4% PFA, and nuclei are stained using 2 μg/ml Hoechst 33342. Fluorescence is analyzed using an imaging cytometer. Cells are considered positive when there are more than four green spots per cell, with a total of 25 fields acquired. The activity of the product is estimated.
Animal Study:^{^[2]}	Animal Models Nude mice Dosages 2 mg/kg Administration s.c.

Cell Assay:^{^[1]}

Cell lines
GFP-LC3 HeLa cells
Concentrations
1 μM
Incubation Time
4 h
Method
GFP-LC3 HeLa cells are starved for 2 h in EBSS plus 10 μM Vps34 compound or DMSO. For mTOR inhibitor, GFP-LC3 H1299 cells are treated with 1 μM AZD8055 for 4 h in fed conditions. Cells are then fixed with 4% PFA, and nuclei are stained using 2 μg/ml Hoechst 33342. Fluorescence is analyzed using an imaging cytometer. Cells are considered positive when there are more than four green spots per cell, with a total of 25 fields acquired. The activity of the product is estimated.

Animal Study:^{^[2]}

Animal Models
Nude mice
Dosages
2 mg/kg
Administration
s.c.

References

Customer Product Validation

: Data from [Data independently produced by , , Urol Oncol, 2018, 36(4):160.e1-160.e13]

Selleck's SAR405 has been cited by 37 publications

STING orchestrates the neuronal inflammatory stress response in multiple sclerosis [ Cell, 2024, 187(15):4043-4060.e30]	PubMed: 38878778
Intercellular transfer of cancer cell invasiveness via endosome-mediated protease shedding [ Nat Commun, 2024, 15(1):1277]	PubMed: 38341434
Targeting autophagy overcomes cancer-intrinsic resistance to CAR-T immunotherapy in B-cell malignancies [ Cancer Commun (Lond), 2024, 44(3):408-432]	PubMed: 38407943
Combining VPS34 inhibitors with STING agonists enhances type I interferon signaling and anti-tumor efficacy [ Mol Oncol, 2024, 10.1002/1878-0261.13619]	PubMed: 38506049
Targeting autophagy as a therapeutic strategy in pediatric acute lymphoblastic leukemia [ Sci Rep, 2024, 14(1):4000]	PubMed: 38369625
Growing Macrophages Regulate High Rates of Solute Flux by Pinocytosis [ bioRxiv, 2024, 2024.10.22.619691]	PubMed: 39484410
Inhibition of phosphoglycerate dehydrogenase induces ferroptosis and overcomes enzalutamide resistance in castration-resistant prostate cancer cells [ Drug Resist Updat, 2023, 70:100985]	PubMed: 37423117
Class 3 PI3K coactivates the circadian clock to promote rhythmic de novo purine synthesis [ Nat Cell Biol, 2023, 25(7):975-988]	PubMed: 37414850
TECPR1 is activated by damage-induced sphingomyelin exposure to mediate noncanonical autophagy [ EMBO J, 2023, 42(17):e113105]	PubMed: 37409525
Partial inhibition of class III PI3K VPS-34 ameliorates motor aging and prolongs health span [ PLoS Biol, 2023, 21(7):e3002165]	PubMed: 37432924

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.