SAR405
Based on 35 publication(s) in Google Scholar
SAR405 is a first-in-class, selective, and ATP-competitive PI3K class III (PIK3C3) isoform Vps34 inhibitor (IC50=1.2 nM; Kd=1.5 nM). SAR405 inhibits autophagy induced either by starvation or by mTOR inhibition. Anticancer activity.
For research use only. We do not sell to patients.
- Purity: 99.74%
- CAS No.: 1523406-39-4
- Formula: C19H21ClF3N5O2
- Molecular Weight:443.85
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
Publications Citing Use of MedChemExpress (MCE) SAR405
More- Signal Transduct Target Ther. 2026 Feb 18;11(1):59. [Abstract]
- Nat Genet. 2021 Apr;53(4):435-444. [Abstract]
- Cell Mol Immunol. 2021 Aug;18(8):2024-2039. [Abstract]
- Nat Cell Biol. 2026 Apr;28(4):812-827. [Abstract]
- Mol Cell. 2021 Mar 18;81(6):1337-1354.e8. [Abstract]
- Nat Commun. 2021 Feb 26;12(1):1322. [Abstract]
- Nat Commun. 2020 Aug 13;11(1):4051. [Abstract]
- Nat Commun. 2018 Jan 18;9(1):291. [Abstract]
- Cell Death Differ. 2025 Sep 1. [Abstract]
- Acta Pharm Sin B. 2025 Dec 18.
- Adv Sci (Weinh). 2024 Aug;11(31):e2308307. [Abstract]
- Cell Death Dis. 2022 Apr 23;13(4):400. [Abstract]
- Acta Pharmacol Sin. 2021 Feb;42(2):301-310. [Abstract]
- ACS Appl Mater Interfaces. 2025 May 21;17(20):29364-29378. [Abstract]
- Antioxidants (Basel). 2022 May 20;11(5):1009. [Abstract]
- J Cell Biol. 2025 Nov 3;224(11):e202411198. [Abstract]
- Phytother Res. 2026 May;40(5):2364-2379. [Abstract]
- Chin Med. 2023 Oct 10;18(1):128. [Abstract]
- Life Sci. 2021 Apr 15:271:119139. [Abstract]
- mBio. 2026 Feb 5:e0359525. [Abstract]
- Int Immunopharmacol. 2025 May 7:157:114799. [Abstract]
- J Infect Dis. 2025 Jul 16:jiaf373. [Abstract]
- Cancers (Basel). 2026 Mar 11;18(6):902. [Abstract]
- J Virol. 2021 Nov 23;95(24):e0153721. [Abstract]
- Biochim Biophys Acta Mol Cell Res. 2019 May;1866(5):793-805. [Abstract]
- Dis Model Mech. 2023 Oct 1;16(10):dmm050206. [Abstract]
- Neuroscience. 2021 Apr 15:460:107-119. [Abstract]
- Thorac Cancer. 2026 Mar;17(5):e70255. [Abstract]
- bioRxiv. 2026 Feb 16.
- Patent. US20250262208A1.
- Patent. US20240309381A1.
- bioRxiv. 2024 Sep 26:2024.09.25.615011. [Abstract]
- bioRxiv. 2024 Feb 5.
- Patent. US20230011398A1.
- Patent. US20210277396A1.
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IF
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RT-PCR
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In Vivo Efficacy Study
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WB
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WB
Biological Activity
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Vps34 1.2 nM (IC50) |
Vps34 1.5 nM (Kd) |
Autophagy |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| Cortical neurone | EC50 |
2.4 μM
Compound: SAR405
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Neuroprotective activity in rat cortical neurons transfected with an mHTT-exon1-Q73 construct in presence of primary corticostriatal co-culture system assessed as rescue from mHTT-induced survival loss by fluorescent reporter based assay
Neuroprotective activity in rat cortical neurons transfected with an mHTT-exon1-Q73 construct in presence of primary corticostriatal co-culture system assessed as rescue from mHTT-induced survival loss by fluorescent reporter based assay
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[PMID: 30840447] |
| HeLa | IC50 |
27 nM
Compound: 69; SAR405
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Inhibition of Vps34 in human HeLa cells expressing GFP-FYVE
Inhibition of Vps34 in human HeLa cells expressing GFP-FYVE
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[PMID: 29211480] |
The activity of SAR405 is next evaluated on a dedicated Vps34 cellular assay using a GFP-FYVE–transfected HeLa cell line[1].
SAR405 prevents autophagy and synergizes with mTOR inhibition in tumor cells. SAR405 prevents autophagosome formation with an IC50 of 42 nM. Treatment of starved cells with SAR405 completely inhibits the conversion to LC3-II in a dose-dependent manner. The effect of SAR405 on autophagy is then investigated. The GFP-LC3 model is used for the HTS and confirmed its activity on starved cells (IC50=419 nM). The conversion of LC3-I into LC3-II is also analyzed by western blotting on wild-type HeLa and H1299 cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 1523406-39-4
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Appearance Solid
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Molecular Weight 443.85
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Formula C19H21ClF3N5O2
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Color Off-white to light yellow
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SMILES
O=C1N(C2=NC(N3[C@H](C)COCC3)=C1)CC[C@@H](C(F)(F)F)N2CC4=CC(Cl)=CN=C4
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (35)
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Journal Impact Factor
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Most Recent
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Signal Transduct Target Ther
Ring finger protein 213 regulates B-cell receptor signaling, metabolism, and development in B lymphocytes. [Abstract]2026 Feb 18;11(1):59. PMID: 41702884 -
Nat Genet
Genome-wide CRISPR screening identifies TMEM106B as a proviral host factor for SARS-CoV-2. [Abstract]2021 Apr;53(4):435-444. PMID: 33686287
SAR405 purchased from MedChemExpress. Usage Cited in: Nat Genet. 2021 Apr;53(4):435-444. [Abstract]
Immunofluorescence staining of LC3B in uninfected or SARS-CoV-2-infected Huh7 cells treated with SAR405 (12.5 μM; 6 h) showed that PI3K type 3 inhibition completely abolished the formation of LC3-positive puncta and induced vacuoles in treated cells.
SAR405 purchased from MedChemExpress. Usage Cited in: Nat Genet. 2021 Apr;53(4):435-444. [Abstract]
Time series experiments showed an early stage post-receptor binding effect of the PI3K type 3 inhibitor SAR405 on HCoV-229E infection. Huh7 cells were infected, treated with SAR405 at different timepoints, and followed by determination of viral RNA levels at 10 hours post infection by qPCR. Inhibition of HCoV-229E by SAR405 occurred later in the viral life cycle than the attachment stage, as benchmarked by the attachment inhibitor Urtica dioica agglutinin (UDA), but earlier than the onset of intracellular replication as identified using the viral RNA synthesis inhibitor remdesivir.
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Cell Mol Immunol
Pik3c3 deficiency in myeloid cells imparts partial resistance to experimental autoimmune encephalomyelitis associated with reduced IL-1β production. [Abstract]2021 Aug;18(8):2024-2039. PMID: 33235386
SAR405 purchased from MedChemExpress. Usage Cited in: Cell Mol Immunol. 2021 Aug;18(8):2024-2039. [Abstract]
PIK3C3 was an important regulator of myeloid cell function and a potential therapeutic target for treating EAE. SAR405 treatment delayed the onset of EAE. EAE was induced by active immunization with MOG35–55 peptide, and SAR405 (10 mg/kg; once daily) was administered orally starting 3 days after immunization for 11 consecutive days.
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Nat Cell Biol
TOLLIP targets GSDME-NT-carrying endocytic vesicles for autophagy to regulate pyroptosis and chemotherapy efficacy. [Abstract]2026 Apr;28(4):812-827. PMID: 41803502 -
Mol Cell
Systematically defining selective autophagy receptor-specific cargo using autophagosome content profiling. [Abstract]2021 Mar 18;81(6):1337-1354.e8. PMID: 33545068 -
Nat Commun
VPS34 K29/K48 branched ubiquitination governed by UBE3C and TRABID regulates autophagy, proteostasis and liver metabolism. [Abstract]2021 Feb 26;12(1):1322. PMID: 33637724 -
Nat Commun
Clearance of HIV infection by selective elimination of host cells capable of producing HIV. [Abstract]2020 Aug 13;11(1):4051. PMID: 32792548 -
Nat Commun
Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures. [Abstract]2018 Jan 18;9(1):291. PMID: 29348617 -
Cell Death Differ
TAB2 controls a TAK1-independent cell death checkpoint at the level of TNFR1 complex II in the TNF pathway. [Abstract]2025 Sep 1. PMID: 40890346 -
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Adv Sci (Weinh)
Aloperine Suppresses Cancer Progression by Interacting with VPS4A to Inhibit Autophagosome-lysosome Fusion in NSCLC. [Abstract]2024 Aug;11(31):e2308307. PMID: 39166458 -
Cell Death Dis
Targeting DRD2 by the antipsychotic drug, penfluridol, retards growth of renal cell carcinoma via inducing stemness inhibition and autophagy-mediated apoptosis. [Abstract]2022 Apr 23;13(4):400. PMID: 35461314 -
Acta Pharmacol Sin
2021 Feb;42(2):301-310. PMID: 32699265 -
ACS Appl Mater Interfaces
Ultrasound Visualization of Spatiotemporal Autophagy-Regulated Nanodroplets for Amplifying ICB in Melanoma via Remodeling Tumor Inflammatory Microenvironment. [Abstract]2025 May 21;17(20):29364-29378. PMID: 40331917 -
Antioxidants (Basel)
Diclofenac: A Nonsteroidal Anti-Inflammatory Drug Inducing Cancer Cell Death by Inhibiting Microtubule Polymerization and Autophagy Flux. [Abstract]2022 May 20;11(5):1009. PMID: 35624874 -
J Cell Biol
PI(3)P coordinates SNX17- and SNX27-dependent protein recycling for long-term synaptic plasticity. [Abstract]2025 Nov 3;224(11):e202411198. PMID: 40920104 -
Phytother Res
Z-Guggulsterone Inhibits Triple-Negative Breast Cancer Progression by Blocking Autophagosome-Lysosome Fusion via OGT-Mediated SNAP29 O-GlcNAcylation. [Abstract]2026 May;40(5):2364-2379. PMID: 41684288 -
Chin Med
Isoforskolin modulates AQP4-SPP1-PIK3C3 related pathway for chronic obstructive pulmonary disease via cAMP signaling. [Abstract]2023 Oct 10;18(1):128. PMID: 37817209 -
Life Sci
2021 Apr 15:271:119139. PMID: 33539914 -
mBio
2026 Feb 5:e0359525. PMID: 41641997 -
Int Immunopharmacol
TGF-β1 induces autophagy and mediates the effect on macrophages differentiation in primary liver cancer. [Abstract]2025 May 7:157:114799. PMID: 40339499 -
J Infect Dis
2025 Jul 16:jiaf373. PMID: 40668935 -
Cancers (Basel)
Triptolide Triggers Protective Autophagy via ROS Induction in NSCLC: Therapeutic Synergy with Autophagy Inhibition. [Abstract]2026 Mar 11;18(6):902. PMID: 41899507 -
J Virol
Inhibition of Autophagy Suppresses SARS-CoV-2 Replication and Ameliorates Pneumonia in hACE2 Transgenic Mice and Xenografted Human Lung Tissues. [Abstract]2021 Nov 23;95(24):e0153721. PMID: 34550769 -
Biochim Biophys Acta Mol Cell Res
Phosphatidylinositol-3-phosphate-mediated actin domain formation linked to DNA synthesis upon insulin treatment in rat hepatoma-derived H4IIEC3 cells. [Abstract]2019 May;1866(5):793-805. PMID: 30742930
SAR405 purchased from MedChemExpress. Usage Cited in: Biochim Biophys Acta Mol Cell Res. 2019 May;1866(5):793-805. [Abstract]
Serum-starved H4IIEC3 cells are treated with 100 nM ins for 0, 5, 15, and 30 min, and electrophoresed protein extracts subjected to western blotting using antibodies against pAktS473 and Akt.
SAR405 purchased from MedChemExpress. Usage Cited in: Biochim Biophys Acta Mol Cell Res. 2019 May;1866(5):793-805. [Abstract]
Serum-starved H4IIEC3 cells are treated with 100 nM ins for 0, 5, 15, and 30 min and electrophoresed protein extracts subjected to western blotting using antibodies against total or phosphorylated p42/p44 MAPK.
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Dis Model Mech
Glycosphingolipids are linked to elevated neurotransmission and neurodegeneration in a Drosophila model of Niemann Pick type C. [Abstract]2023 Oct 1;16(10):dmm050206. PMID: 37815467 -
Neuroscience
Reduction of Autophagosome Overload Attenuates Neuronal Cell Death After Traumatic Brain Injury. [Abstract]2021 Apr 15:460:107-119. PMID: 33600885 -
Thorac Cancer
Effects of Autophagy Inhibition by SAR405, a Selective VPS34 Inhibitor, on Pleural Mesothelioma Cells. [Abstract]2026 Mar;17(5):e70255. PMID: 41771171 -
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bioRxiv
Single-cell virology: On-chip, quantitative characterization of the dynamics of virus spread from one single cell to another. [Abstract]2024 Sep 26:2024.09.25.615011. PMID: 39386720 -
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Solvent & Solubility
DMSO : ≥ 27 mg/mL (60.83 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
H2O : < 0.1 mg/mL (insoluble)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.63 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.63 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
KiNativ profiling is performed. Jurkat cell lysates are treated with 1 μM of SAR405. After 15-min incubation, the desthiobiotin-ATP-acylphosphate probe is added and incubated for 10 min. Samples are prepared for targeted MS analysis. Briefly, samples are prepared for trypsin digestion (denature and then reduce alkylate) and digested with trypsin, and desthiobiotinylated peptides are enriched on streptavidin resin. Enriched probe-labeled peptides are analyzed by LC tandem MS on a Thermo-LTQ ion trap mass spectrometer using proprietary data collection methodology. All quantification is performed by extracting characteristic fragment ion signals from targeted MS/MS spectra and comparing signals in control and treated samples[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (279 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Ronan B, et al. A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat Chem Biol. 2014 Dec;10(12):1013-9. [Content Brief]
[2]. Pasquier B. SAR405, a PIK3C3/Vps34 inhibitor that prevents autophagy and synergizes with MTOR inhibition in tumor cells. Autophagy. 2015 Apr 3;11(4):725-6. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.2530 mL | 11.2651 mL | 22.5301 mL | 56.3253 mL |
| 5 mM | 0.4506 mL | 2.2530 mL | 4.5060 mL | 11.2651 mL | |
| 10 mM | 0.2253 mL | 1.1265 mL | 2.2530 mL | 5.6325 mL | |
| 15 mM | 0.1502 mL | 0.7510 mL | 1.5020 mL | 3.7550 mL | |
| 20 mM | 0.1127 mL | 0.5633 mL | 1.1265 mL | 2.8163 mL | |
| 25 mM | 0.0901 mL | 0.4506 mL | 0.9012 mL | 2.2530 mL | |
| 30 mM | 0.0751 mL | 0.3755 mL | 0.7510 mL | 1.8775 mL | |
| 40 mM | 0.0563 mL | 0.2816 mL | 0.5633 mL | 1.4081 mL | |
| 50 mM | 0.0451 mL | 0.2253 mL | 0.4506 mL | 1.1265 mL | |
| 60 mM | 0.0376 mL | 0.1878 mL | 0.3755 mL | 0.9388 mL |