AGI-5198

SKU: orb1306471

Description

AGI-5198 is a potent and selective small molecule inhibitor targeting the neomorphic activity of mutant IDH1 enzymes, specifically the R132H and R132C variants, with IC50 values of 70 nM and 160 nM, respectively. It is a valuable research tool for investigating the role of oncometabolite 2-HG in cancers like glioma and AML, both in cellular assays and in vivo models.

Research Area

Metabolism Research

Key Properties

• CAS Number: 1355326-35-0
• MW: 462.56
• Purity: >98%
• Formula: C₂₇H₃₁FN₄O₂
• SMILES: Cc1nccn1CC(=O)N(C(C(=O)NC1CCCCC1)c1ccccc1C)c1cccc(F)c1
• Target: Dehydrogenase (GAPDH, GPDH, IMPDH, PHGDH, LDH, DHODH, ALDH, GDH, IDH, UGDH, DPD, DHPDH, KGDH, PDH, and MDH)
• Solubility: Soluble in DMSO (up to 10 mg/ml) or in Ethanol (up to 5 mg/ml)

Bioactivity

• Target IC50:
  R132H IDH1:70 nM|R132C IDH1:0.16 μM
• In Vivo:
  AGI-5198 showed some anti-tumor efficacy against TS603 glioma cell line and dose-dependently inhibited R-2HG production. Under the condition of almost complete inhibition of R-2HG, AGI-5198 induced demethylation of histone H3K9me3, and induced the expression of genes related to glial gene differentiation. In genome-wide DNA methylation, AGI-5198 inhibited the growth of mIDH1-impaired IDH1 mutant, but wild-type growth was hardly affected.AGI-5198 significantly inhibited mutant IDH1 (R132H-IDH1 and R132C-IDH1), but did not inhibit the growth of wild-type IDH1 (IC50>100 μM) or IDH1 (IC50>100 μM) or wild-type IDH1 (IC50>100 μM), but very weakly inhibited any of the IDH2 isoforms (R140Q, R172K, wild-type) (IC50>100 μM).
• In Vitro:
  AGI-5198 showed some anti-tumor efficacy against TS603 glioma cell line and dose-dependently inhibited R-2HG production. Under the condition of almost complete inhibition of R-2HG, AGI-5198 induced demethylation of histone H3K9me3, and induced the expression of genes related to glial gene differentiation. In genome-wide DNA methylation, AGI-5198 inhibited the growth of mIDH1-impaired IDH1 mutant, but wild-type growth was hardly affected.AGI-5198 significantly inhibited mutant IDH1 (R132H-IDH1 and R132C-IDH1), but did not inhibit the growth of wild-type IDH1 (IC50>100 μM) or IDH1 (IC50>100 μM) or wild-type IDH1 (IC50>100 μM), but very weakly inhibited any of the IDH2 isoforms (R140Q, R172K, wild-type) (IC50>100 μM).
• Cell Research:
  AGI-5198 is dissolved in DMSO.TS603 cells are grown in medium containing either AGI-5198 (1.5 μM) or DMSO vehicle control.One week prior to harvest cells are ransferred to differentiation medium (DMEM F12; 15 mM HEPES; 0.06% glucose; B27 without vitamin A; N2; Insulin/transferrin; 1% FBS) containing freshly added retinoic acid (1 μM).ChIP of non-crosslinked cells is then carried out using established ChIP methods.350 μg of lysate is immunoprecipitated-using anti-H3K9Me3,H3K27me3 or Rabbit Control IgG.After washing,ChIP DNA is eluted from protein G beads and analyzed by RT-PCR using SYBR green.Relative occupancy is calculated using the standard curve method and fold enrichment versus IgG.Enrichment in AGI- 5198-treated cells is normalized to vehicle control.Means and standard deviation are calculated from 4 technical replicates.

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

AGI 5198, AGI5198, AGI-5198, inhibit, Isocitrate Dehydrogenase (IDH), IsocitrateDehydrogenase(IDH), IsocitrateDehydrogenase, Isocitrate Dehydrogenase, IDH-C35, IDH, Inhibitor, R132C-IDH1, R132H-IDH1

Compound Identifiers

PubChem CID

56645356