Size | Price | |
---|---|---|
50mg | ||
100mg | ||
250mg | ||
500mg | ||
1g |
Telaglenastat HCl (formerly CB839; CB-839) is an orally bioavailable small molecule glutaminase inhibitor with anticancer activity. It inhibits glutaminase with IC50 of 24 nM for recombinant human GAC. CB-839 exhibits time-dependent and slowly reversible kinetics. IC50 values for glutaminase inhibition by CB-839 following preincubation with rHu-GAC for-1 hour are < 50 nmol/L, at least 13-fold lower than with BPTES. CB-839 has antiproliferative activity in a triple-negative breast cancer (TNBC) cell line, HCC-1806, while no antiproliferative activity is observed in an estrogen receptor–positive cell line, T47D. Telaglenastat is currently in Phase 1 study in combination with cabozantinib in patients with advanced renal cell carcinoma. Telaglenastat is novel glutaminase inhibitor specifically designed to block glutamine consumption in tumor cells. RCC tumors commonly exhibit metabolic alterations that increase their dependence on glutamine. In preclinical studies, telaglenastat produced synergistic antitumor effects when used in combination with standard-of-care RCC therapies including cabozantinib.
ln Vitro |
In HCC1806 and MDA-MB-231 cells, telaglenastat (CB-839) (0.1-1000 nM; 72 hours) exhibits antiproliferative activity with IC50s of 49 nM and 26 nM, respectively[1]. MDA-MB-231 and HCC1806 cells undergo apoptosis when exposed to telaglenastat (CB-839) (1 μM; 72 hours) because it activates caspase 3/7[1].
|
---|---|
ln Vivo |
In TNBC xenograft models, telaglenastat (CB-839) (200 mg/kg; po; twice daily for 28 days) exhibits anticancer activity[1].
|
Cell Assay |
Cell Proliferation Assay[1]
Cell Types: HCC1806, MDA-MB-231 cells Tested Concentrations: 0.1, 1, 10, 100, 1000 nM Incubation Duration: 72 hrs (hours) Experimental Results: Has a potent effect on the proliferation of the two TNBC cell lines (IC50 of 49 nM and 26 nM for HCC1806 and MDA-MB-231 cells). Apoptosis Analysis[1] Cell Types: MDA-MB-231, HCC1806 cells Tested Concentrations: 1 μM Incubation Duration: 72 hrs (hours) Experimental Results: Caspase 3/7 activation. |
Animal Protocol |
Animal/Disease Models: Female nu/nu (nude) mice with age 4–6 weeks (TNBC patient- derived xenograft model)[1]
Doses: 200 mg/kg Route of Administration: Oral administration; twice (two times) daily for 28 days Experimental Results: Suppressed tumor growth by 61% relative to vehicle control at the end of study. |
References |
[1]. Gross MI, et al. Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Mol Cancer Ther. 2014 Apr;13(4):890-901.
[2]. Biancur DE, et al. Compensatory metabolic networks in pancreatic cancers upon perturbation of glutaminemetabolism. Nat Commun. 2017 Jul 3;8:15965. [3]. Zhou WJ, et al. Estrogen inhibits autophagy and promotes growth of endometrial cancer by promoting glutamine metabolism. Cell Commun Signal. 2019 Aug 20;17(1):99. |
Molecular Formula |
C26H25CLF3N7O3S
|
---|---|
Molecular Weight |
608.035012960434
|
CAS # |
1874231-60-3
|
Related CAS # |
Telaglenastat;1439399-58-2
|
SMILES |
Cl.S1C(NC(CC2C=CC=CN=2)=O)=NN=C1CCCCC1=CC=C(N=N1)NC(CC1C=CC=C(C=1)OC(F)(F)F)=O
|
Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
---|
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.6446 mL | 8.2231 mL | 16.4463 mL | |
5 mM | 0.3289 mL | 1.6446 mL | 3.2893 mL | |
10 mM | 0.1645 mL | 0.8223 mL | 1.6446 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
FLT3 inhibitor AC220 impairs glutamine flux comparable to the glutaminase inhibitor CB-839 in AML cells.Exp Hematol.2018 Feb;58:52-58. th> |
---|
AC220 and CB-839 have combinatorial effects on cell viability, glutathione, mitochondrial ROS, and apoptosis in AML cells. td> |
CB-839 cooperates with AC220 in eliminating FLT3-mutated AML cells in vivo and improves survival.Exp Hematol.2018 Feb;58:52-58. td> |