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Chemical Structure| 1523406-39-4 Chemical Structure| 1523406-39-4

Structure of SAR405
CAS No.: 1523406-39-4

Chemical Structure| 1523406-39-4

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SAR405 is a first-in-class, selective, ATP-competitive PI3K class III (PIK3C3) isoform Vps34 inhibitor with an IC50 of 1.2 nM and Kd of 1.5 nM. It inhibits autophagy induced by either starvation or mTOR inhibition and exhibits anticancer activity.

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Product Details of SAR405

CAS No. :1523406-39-4
Formula : C19H21ClF3N5O2
M.W : 443.85
SMILES Code : O=C1C=C(N2[C@H](C)COCC2)N=C3N(CC4=CC(Cl)=CN=C4)[C@H](C(F)(F)F)CCN31
MDL No. :MFCD28411361
InChI Key :SPDQRCUBFSRAFI-DOMZBBRYSA-N
Pubchem ID :72709209

Safety of SAR405

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of SAR405

PI3K-AKT

Isoform Comparison

Biological Activity

Description
SAR405 is a pioneering, selective, ATP-competitive inhibitor of the PI3K class III isoform Vps34 (PIK3C3) (IC50=1.2 nM; KD=1.5 nM). It suppresses autophagy triggered by either starvation or mTOR inhibition and exhibits anticancer properties [1][2].
Target
  • Vps34

    Vps34, IC50:1.2 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
GFP-FYVE HeLa cells 27 nM Assessing IC50 activity of SAR405 PMC4502822
retinal ganglion cells 1 μM 4 hours Combined administration of AlloP with SAR405 induced severe degeneration in retinal neurons at 75 μM Hg, significantly increasing SQSTM1 protein levels, indicating that SAR405 inhibited AlloP-induced autophagy flux. PMC8032250
HNSCC cells 7.92 μM 72 hours To evaluate the inhibitory effect of SAR405 on HNSCC cell proliferation, results showed that SAR405 significantly inhibited HNSCC cell proliferation. PMC5712244
CAF cells 1.0 μM 6 hours To evaluate the inhibitory effect of SAR405 on CAF cell autophagy, results showed that SAR405 significantly inhibited CAF cell autophagy. PMC5712244
B16-F10 melanoma cells 10 µM 48 hours Inhibited autophagy flux and induced CCL5 and CXCL10 expression PMC7190323
CT26 CRC cells 10 µM 48 hours Inhibited autophagy flux and induced CCL5 and CXCL10 expression PMC7190323
A549 5, 10, 20 µM 24 hours Inhibition of autophagic flux, evidenced by the accumulation of p62 and LC3-I, and suppressed conversion of LC3-I to LC3-II PMC11354248

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Experimental autoimmune encephalomyelitis (EAE) model Oral 50 mg/kg twice daily for 3.5 months SAR405 treatment delayed the onset of EAE and reduced the cumulative disease score. PMC8322046
rat glaucoma model intraperitoneal injection 160 mg/kg/day Once daily for 4 days Co-administration of AlloP with SAR405 in the glaucoma model significantly reduced LC3B-II levels and increased SQSTM1 protein levels, indicating that SAR405 inhibited AlloP-induced autophagy flux. PMC8032250
nude mice HNSCC xenograft model intratumoral injection 1 μM once daily for two weeks To evaluate the inhibitory effect of SAR405 on HNSCC tumor growth, results showed that SAR405 significantly inhibited HNSCC tumor growth and had a better effect when combined with cisplatin. PMC5712244
Mice B16-F10 melanoma and CT26 colorectal cancer models Oral 10 μM SAR405 5 days per week, continuous treatment Inhibited tumor growth and improved mice survival, induced infiltration of NK, CD8+, and CD4+ T effector cells PMC7190323

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.25mL

0.45mL

0.23mL

11.27mL

2.25mL

1.13mL

22.53mL

4.51mL

2.25mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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