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Chemical Structure| 1401090-53-6 Chemical Structure| 1401090-53-6

Structure of Ibiglustat
CAS No.: 1401090-53-6

Chemical Structure| 1401090-53-6

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Ibiglustat is a potent and selective glucosylceramide synthase inhibitor and ceramide glucosyltransferase inhibitor.

Synonyms: Venglustat; SAR402671; GZ/SAR402671

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Product Details of Ibiglustat

CAS No. :1401090-53-6
Formula : C20H24FN3O2S
M.W : 389.49
SMILES Code : O=C(O[C@@H]1CN2CCC1CC2)NC(C)(C3=CSC(C4=CC=C(F)C=C4)=N3)C
Synonyms :
Venglustat; SAR402671; GZ/SAR402671
MDL No. :MFCD28502073
InChI Key :YFHRCLAKZBDRHN-MRXNPFEDSA-N
Pubchem ID :60199242

Safety of Ibiglustat

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H320-H335
Precautionary Statements:P264-P270-P301+P312-P330

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
colonoids 5 μmol/L 24 hours Inhibition of glucosylceramide synthase (GCS) activity, reducing glucosylceramide levels, leading to colonoid bursting in the presence of BFT FASEB J. 2020 Dec;34(12):15922-15945
HCT116 cells 0.5 μM 72 hours Evaluate the inhibitory effect of Ibiglustat on NTMT1, showing significant reductions in me3-RCC1 and me3-SET levels at 1 μM J Med Chem. 2022 Sep 22;65(18):12334-12345
HEK293 cells 1 μM 3 days Evaluate the inhibitory effect of venglustat on me3-RCC1 and me3-SET in HEK293 cells, showing significant inhibition at 1 μM J Med Chem. 2023 Jan 26;66(2):1601-1615

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice GBA-related synucleinopathy model Oral 0.03% wt/wt 8 months To evaluate the effects of sustained GCS inhibition on disease pathologies, results showed venglustat significantly reduced glycosphingolipid accumulation and improved cognitive deficits. Sci Rep. 2021 Oct 22;11(1):20945
Mice Neurological Gaucher disease model Oral 15 mg Once daily for 1 year To evaluate the safety and tolerability of venglustat and measure changes in the concentration of glucosylceramide and glucosylsphingosine in CSF. Results showed detectable venglustat in CSF and sustained reductions in glucosylceramide and glucosylsphingosine concentrations in 10 patients. Brain. 2023 Feb 13;146(2):461-474
C57BL/6 mice Normal mice and CBE-induced Gaucher disease type 3 mouse model Intraperitoneal injection 10 mg/kg Once daily for 14 days Evaluate the effect of compound 17 in reducing brain glucosylceramide and glucosylsphingosine, results showed that at 10 mg/kg dose, compound 17 had comparable effects to venglustat, reducing brain GlcCer and glucosylsphingosine by 19% and 39%, respectively ACS Chem Neurosci. 2020 Oct 21;11(20):3464-3473
Mice GBA11/L444P knock-in mice Oral 60 mg/kg body weight/day Starting 1 week after injections until the day of death To assess the effect of venglustat on α-synuclein inclusion formation, showing no significant reduction in hippocampal or SNc α-synuclein inclusions. J Neurosci. 2023 Jan 18;43(3):501-521

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT02228460 Fabry Disease PHASE2 COMPLETED 2025-09-16 Investigational Site Number 84... More >>0002, Atlanta, Georgia, 30322, United States|Investigational Site Number 840003, Cincinnati, Ohio, 45229, United States|Investigational Site Number 840001, Fairfax, Virginia, 22030, United States|Investigational Site Number 250001, Garches, 92380, France|Investigational Site Number 616001, Warszawa, 04-730, Poland|Investigational Site Number 643002, Moscow, 125167, Russian Federation|Investigational Site Number 826003, Birmingham, B15 2TH, United Kingdom|Investigational Site Number 826002, Cambridge, CB2 OQQ, United Kingdom Less <<
NCT06418620 Healthy Volunteers PHASE1 COMPLETED 2020-08-07 Prism Research Site Number : 8... More >>400001, Saint Paul, Minnesota, 55114, United States Less <<
NCT02489344 Fabry Disease PHASE2 COMPLETED 2018-11-20 Investigational Site Number 84... More >>0002, Atlanta, Georgia, 30322, United States|Investigational Site Number 840003, Cincinnati, Ohio, 45229, United States|Investigational Site Number 840001, Fairfax, Virginia, 22030, United States|Investigational Site Number 250001, Garches, 92380, France|Investigational Site Number 616001, Warszawa, 04-730, Poland|Investigational Site Number 643002, Moscow, 125167, Russian Federation|Investigational Site Number 826002, Cambridge, CB2 OQQ, United Kingdom Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.57mL

0.51mL

0.26mL

12.84mL

2.57mL

1.28mL

25.67mL

5.13mL

2.57mL

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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