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Chemical Structure| 1439399-58-2 Chemical Structure| 1439399-58-2

Structure of Telaglenastat
CAS No.: 1439399-58-2

Chemical Structure| 1439399-58-2

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Telaglenastat (CB-839) is a first-in-class, selective, reversible, and orally active glutaminase 1 (GLS1) inhibitor. It selectively inhibits GLS1 splice variants KGA (kidney-type glutaminase) and GAC (glutaminase C) with IC50 values of 23 nM and 28 nM for endogenous glutaminase in mouse kidney and brain, respectively. Telaglenastat induces autophagy and has antitumor activity.

Synonyms: CB-839; GLS1 Inhibitor III

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Product Details of Telaglenastat

CAS No. :1439399-58-2
Formula : C26H24F3N7O3S
M.W : 571.57
SMILES Code : O=C(NC1=NN=C(CCCCC2=NN=C(NC(CC3=CC=CC(OC(F)(F)F)=C3)=O)C=C2)S1)CC4=NC=CC=C4
Synonyms :
CB-839; GLS1 Inhibitor III
MDL No. :MFCD28167826
InChI Key :PRAAPINBUWJLGA-UHFFFAOYSA-N
Pubchem ID :71577426

Safety of Telaglenastat

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

Isoform Comparison

Biological Activity

Target
  • glutaminase

    Glutaminase, IC50:24 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
FaDu cells 10 nM 48 h Telaglenastat did not significantly affect the size of FaDu spheroids. PMC7897292
Pmel-1 T cells 1 µM 6 h CB-839 minimally altered glutamate and αKGA levels in Pmel-1 T cells PMC7933078
A375HG melanoma cells 1 µM 6 h CB-839 significantly reduced glutamate and αKGA levels in A375HG cells PMC7933078
SK-LMS-1 cells 1 μM 48 h To evaluate the effect of CB-839 on the proliferation and viability of SK-LMS-1 cells, results showed that CB-839 significantly inhibited cell proliferation and viability. PMC6981153
HT1080 cells 1 μM 48 h To evaluate the effect of CB-839 on the proliferation and viability of HT1080 cells, results showed that CB-839 significantly inhibited cell proliferation and viability. PMC6981153
KPH2-7215 cells 1 μM 48 h To evaluate the effect of CB-839 on the proliferation and viability of KPH2-7215 cells, results showed that CB-839 significantly inhibited cell proliferation and viability. PMC6981153
KP-6634 cells 1 μM 48 h To evaluate the effect of CB-839 on the proliferation and viability of KP-6634 cells, results showed that CB-839 significantly inhibited cell proliferation and viability. PMC6981153
HN5 cells 10 nM 48 h Telaglenastat significantly reduced the size of CAL-27 and HN5 spheroids and increased oxidative stress and DNA damage. PMC7897292
CAL-27 cells 10 nM 48 h Telaglenastat significantly reduced the size of CAL-27 and HN5 spheroids and increased oxidative stress and DNA damage. PMC7897292
Patient MCL cells 11.3 µM 72 h Telaglenastat inhibited the proliferation of patient MCL cells with an IC50 of 11.3 µM. PMC10230437
MCL cell lines 0.22-9.2 µM 72 h Telaglenastat inhibited the proliferation of MCL cell lines with an IC50 of 0.22-9.2 µM. PMC10230437
Autologous tumor-infiltrating lymphocytes (TILs) 1 µM 12 h CB-839 caused minimal inhibition of glutamine consumption and OCR in TILs PMC7933078
Patient-derived melanoma cell lines 1 µM 12 h CB-839 significantly reduced glutamine consumption in melanoma cells PMC7933078
SiHa PTEN−/− cells 200 nM 96 h Assess cell viability, Telaglenastat treatment significantly reduced cell survival PMC8208465
SiHa cells 200 nM 96 h Assess cell viability, Telaglenastat treatment had minimal effect on cell survival PMC8208465
CaSki cells 200 nM 96 h Assess cell viability, Telaglenastat treatment reduced cell survival PMC8208465
LN229 20 nM 24 h Evaluate the cytotoxicity of nanomedicine on LN229 cells, results showed weaker inhibition of cell growth at 20 nM concentration PMC9141725
U87 20 nM 24 h Evaluate the cytotoxicity of nanomedicine on U87 cells, results showed significant inhibition of cell growth at 20 nM concentration PMC9141725
NCH644 20 nM 24 h Evaluate the cytotoxicity of nanomedicine on NCH644 cells, results showed significant inhibition of cell growth at 20 nM concentration PMC9141725
GBM1 20 nM 24 h Evaluate the cytotoxicity of nanomedicine on GBM1 cells, results showed significant inhibition of cell growth at 20 nM concentration PMC9141725

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice KP and KPH2 mouse models Oral 200 mg/kg Twice daily for 2-3 weeks To evaluate the effect of CB-839 on tumour growth in KP and KPH2 mouse models, results showed that CB-839 significantly inhibited tumour growth. PMC6981153
Nude mice HN5 and CAL-27 xenograft models Oral gavage 200 mg/kg Twice daily for 14 days Combination treatment of telaglenastat with ionizing radiation significantly reduced tumor volume in CAL-27 xenograft models compared to telaglenastat or ionizing radiation alone. PMC7897292
NSG mice Z138 cell-derived xenograft model Oral 200 mg/kg Twice daily, continuous treatment Telaglenastat significantly inhibited the growth of Z138 xenograft tumors and prolonged mouse survival. PMC10230437
Mice B16-F10 melanoma model Oral 200 mg/kg Twice daily for one month CB-839 in combination with Pmel-1 T cell therapy significantly enhanced anti-tumor activity PMC7933078
Nude mice CaSki and SiHa xenograft models Oral gavage 50 mg/kg, 100 mg/kg, 200 mg/kg Three times per week for 37 days Assess the effect of Telaglenastat monotherapy on tumor growth, Telaglenastat significantly inhibited tumor growth PMC8208465

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.75mL

0.35mL

0.17mL

8.75mL

1.75mL

0.87mL

17.50mL

3.50mL

1.75mL

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