B4799-5mg | CB-839 [1439399-58-2] Clinisciences

Background

CB-839(Telaglenastat) is a potent, selective, and orally bioavailable glutaminase inhibitor with IC50 of 24 nM for recombinant human GAC(glutaminase C)[1].

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[1].

In the mouse JIMT-1 xenograft model, CB-839 alone (200 mg/kg, p.o.) results in 54% tumor growth inhibition (TGI) relative to vehicle control, combination of CB-839 (200 mg/kg, p.o.) with paclitaxel (10 mg/kg, p.o.) largely suppresses the regrowth of the tumors resulting in a TGI relative to vehicle control of 100%[1].

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.

Product Citation

1. Yong Bian, Gang Yin, et al. "Degradation of HIF-1α induced by curcumol blocks glutaminolysis and inhibits epithelial-mesenchymal transition and invasion in colorectal cancer cells." Cell Biol Toxicol. 2022 Jan 27. PMID: 35083610
2. Momcilovic M, Bailey ST, et al. "The GSK3 Signaling Axis Regulates Adaptive Glutamine Metabolism in Lung Squamous Cell Carcinoma." Cancer Cell. 2018 May 14;33(5):905-921.e5. PMID: 29763624

Chemical Properties

Storage	Store at -20°C
M.Wt	571.57
Cas No.	1439399-58-2
Formula	C₂₆H₂₄F₃N₇O₃S
Solubility	≥28.6 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
Chemical Name	2-(pyridin-2-yl)-N-(5-(4-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridazin-3-yl)butyl)-1,3,4-thiadiazol-2-yl)acetamide
SDF	Download SDF
Canonical SMILES	FC(F)(F)OC1=CC(CC(NC2=NN=C(CCCCC3=NN=C(NC(CC4=NC=CC=C4)=O)S3)C=C2)=O)=CC=C1
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment [1]:
Cell lines	TNBC cell lines HCC1806 and MDA-MB-231, T47D cell line
Preparation method	Soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reacting condition	1 μmol/L, 4 hours
Applications	CB-839 treatment showed a potent effect on the proliferation of HCC1806 and MDA-MB-231 cells with the IC50 of 20–55 nmol/L. CB-839 (1 μmol/L) inhibited the metabolism of glutamine, the rates of glutamine consumption and glutamate production in HCC1806 and T47D cell lines. TNBC cell lines exhibited greater sensitivity as measured by the extent of cell growth or cell loss following treatment with 1 μmol/L CB-839 for 72 hours. CB-839 (1 μmol/L, 72 hours) showed antiproliferative activity on breast cancer cell lines.
Animal experiment [1]:
Animal models	Scid/Beige mice bearing orthotopically implanted HCC1806 tumors, Patient-derived TNBC and JIMT-1 cell line xenograft models
Dosage form	Oral administration, 200 mg/kg, twice daily
Application	In primary patient-derived TNBC mouse model, oral dosing of single agent CB-839 (200 mg/kg twice daily) suppressed tumor growth. In the mouse JIMT-1 xenograft model, oral dosing of CB-839 alone (200 mg/kg twice daily) resulted in 54% tumor growth inhibition (TGI). Combination of CB-839 (200 mg/kg, p.o.) with paclitaxel (10 mg/kg, p.o.) largely suppressed the regrowth of the tumors resulting in a TGI relative to vehicle control of 100%.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Gross M I, Demo S D, Dennison J B, et al. Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer[J]. Molecular cancer therapeutics, 2014, 13(4): 890-901.

Quality Control

Purity = 99.69%

Chemical structure

Related Biological Data

CB-839 [1439399-58-2]

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