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Chemical Structure| 1355326-35-0 Chemical Structure| 1355326-35-0

Structure of AGI-5198
CAS No.: 1355326-35-0

Chemical Structure| 1355326-35-0

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AGI-5198 is a potent and selective inhibitor of IDH1 R132H and R132C mutants with IC50 values of 0.07 and 0.16 µM, respectively, but not wild-type IDH1, wild-type IDH2, or IDH2 mutants.

Synonyms: IDH-C35

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Product Details of AGI-5198

CAS No. :1355326-35-0
Formula : C27H31FN4O2
M.W : 462.56
SMILES Code : O=C(NC1CCCCC1)C(N(C2=CC=CC(F)=C2)C(CN3C=CN=C3C)=O)C4=CC=CC=C4C
Synonyms :
IDH-C35
MDL No. :MFCD24848688
InChI Key :FNYGWXSATBUBER-UHFFFAOYSA-N
Pubchem ID :56645356

Safety of AGI-5198

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P280-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • Dehydrogenase

    R132H-IDH1, IC50:70 nM

    R132C-IDH1, IC50:0.16 μM

In Vitro:

Cell Line
Concentration Treated Time Description References
E6E7hTERT cells 1 or 10 μM 72 h (pre-treatment), 28 days (for colony count) To assess the effect of AGI-5198 on cell proliferation and clonogenicity. No significant change in clonogenicity was observed except a modest decrease in mutant IDH1 expressing cells only at higher concentrations. PMC5065766
RBE cells 0–40 µM 72 hours To evaluate the antitumor activity of AGI-5198 on RBE cells, the results showed that AGI-5198 in combination with aloperine had significant synergistic effects. PMC11395030
HCCC-9810 cells 0–40 µM 72 hours To evaluate the antitumor activity of AGI-5198 on HCCC-9810 cells, the results showed that AGI-5198 in combination with aloperine had weak synergistic effects. PMC11395030
IDHmut cells 10 μM 72 hours Inhibiting 2-HG production restored PC and PE levels to those observed in IDHwt cells. PMC5881177
TS603 glioma cells 0.07 µM 2 days AGI-5198 inhibited the ability of the mutant enzyme (mIDH1) to produce R-2HG and inhibited colony formation of TS603 glioma cells in soft agar. PMC3985613
TS676 and TS516 glioma cells 20 µM AGI-5198 did not affect colony formation of wild-type IDH1 glioma cells. PMC3985613
SF10602 cells 5µM 1 week Inhibition of mIDH1 leads to upregulation of replication-associated pathways and reduction in 2HG levels PMC10159884
MGG119 cells 5µM 1 week Inhibition of mIDH1 leads to significant reduction in ZMYND8 expression PMC10159884
LC1035 cells 5µM 1 week Inhibition of mIDH1 leads to significant reduction in ZMYND8 expression PMC10159884
MGG119 5µM 1 week To evaluate the effect of AGI-5198 on ZMYND8 protein expression PMC10159884
SF10602 5µM 1 week To evaluate changes in transcriptome and epigenome after mIDH1 inhibition PMC10159884
LC1035 5µM 1 week To evaluate the effect of AGI-5198 on ZMYND8 protein expression PMC10159884

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice R132H-IDH1 glioma xenografts Oral 450 mg/kg Daily treatment for 3 weeks AGI-5198 significantly inhibited the growth of R132H-IDH1 mutant glioma xenografts but had no effect on wild-type IDH1 glioma. PMC3985613
Mice intracranial mIDH1 glioma model Intraperitoneal injection 10 mg/Kg 5 days per week for two weeks To evaluate the therapeutic efficacy of Pamiparib combined with radiation in mIDH1 glioma PMC10159884

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.16mL

0.43mL

0.22mL

10.81mL

2.16mL

1.08mL

21.62mL

4.32mL

2.16mL

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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