CB-839
Description In vitro In vivo- Product Name
- CB-839
- CAS No.
- 1439399-58-2
- Chemical Name
- CB-839
- Synonyms
- CB-839;CPD1593;CS-1813;Telaglenastat;CB-839 (CB839;CB-839,TELAGLENASTAT;CB839 ;CB 839 ;CB-839;Telaglenastat (CB-839);GLS1 Inhibitor III, CB-839;Telaglenastat, 10 mM in DMSO
- CBNumber
- CB92718863
- Molecular Formula
- C26H24F3N7O3S
- Formula Weight
- 571.57
- MOL File
- 1439399-58-2.mol
CB-839 Property
- Melting point:
- 186- 189° C
- Density
- 1.430±0.06 g/cm3(Predicted)
- storage temp.
- +2C to +8C
- solubility
- Soluble in DMSO.
- form
- Yellow solid
- pka
- 8.25±0.50(Predicted)
- color
- Pale yellow
- Stability:
- Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months.
- InChIKey
- PRAAPINBUWJLGA-UHFFFAOYSA-N
- SMILES
- C1(CC(NC2=NN=C(CCCCC3=NN=C(NC(CC4=CC=CC(OC(F)(F)F)=C4)=O)C=C3)S2)=O)=NC=CC=C1
Hazard and Precautionary Statements (GHS)
- Symbol(GHS)
-
- Signal word
- Warning
- Hazard statements
-
H302Harmful if swallowed
H315Causes skin irritation
H319Causes serious eye irritation
H335May cause respiratory irritation
- Precautionary statements
-
P261Avoid breathing dust/fume/gas/mist/vapours/spray.
P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.
N-Bromosuccinimide Price
- Product number
- 5.33717
- Product name
- GLS1 Inhibitor III, CB-839 - CAS 1439399-58-2 - Calbiochem
- Packaging
- 10mg
- Price
- $265
- Updated
- 2025/07/31
- Product number
- 22038
- Product name
- CB-839
- Purity
- ≥98%
- Packaging
- 5mg
- Price
- $57
- Updated
- 2024/03/01
- Product number
- 22038
- Product name
- CB-839
- Purity
- ≥98%
- Packaging
- 50mg
- Price
- $302
- Updated
- 2024/03/01
- Product number
- 22038
- Product name
- CB-839
- Purity
- ≥98%
- Packaging
- 1mg
- Price
- $30
- Updated
- 2021/12/16
- Product number
- 22038
- Product name
- CB-839
- Purity
- ≥98%
- Packaging
- 10mg
- Price
- $95
- Updated
- 2024/03/01
CB-839 Chemical Properties,Usage,Production
Description
CB-839 is a potent, selective, and orally bioavailable glutaminase inhibitor with IC50 of 24 nM for recombinant human GAC. Phase 1.
In vitro
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.
In vivo
In the mouse TNBC model, single agent CB-839 (200 mg/kg, p.o.) suppresses tumor growth by 61% relative to vehicle control. 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%.
Description
CB-839 (14393999-58-2)?is a potent (IC50?= 24 nM), selective and orally bioavailable inhibitor of glutaminase (KGA and GAC).1?CB-839 displayed an antiproliferative effect in the triple-negative breast cancer cell line, HCC-1806, but no activity in the estrogen receptor-positive cell line T47D.? CB-839 was able to cause proliferation arrest and apoptosis in acute myeloid leukemia cells without causing cytotoxicity against normal human CD34(+) progenitors.2? Aspartate-glutamate carrier 1 (AGC1) inhibition can synergize with CB-839 to limit tumor growth.3
Uses
CB-839 performs an antileukemic activity. It Inhibits GLS1 genes and reduces oxidative phosphorylation leading to leukamic cell proliferation arrest and apoptosis.
Synthesis
13115-43-0
1439399-45-7
1439399-58-2
In a 250 mL three-necked round-bottomed flask, N-[6-[4-(5-amino-1,3,4-thiadiazol-2-yl)butyl]-3-pyridazinyl]-3-(trifluoromethoxy)benzeneacetamide (5.5 g, 12.3 mmol, 1.0 eq.) was dissolved in N,N-dimethylacetamide (44 mL, 8.0 v/v). Pyridine-2-acetic acid (2.56 g, 14.8 mmol, 1.2 equiv) was added. Propylphosphonic anhydride (50% ethyl acetate solution, 11.0 g, 17.3 mmol, 1.41 eq.) was added dropwise through the addition funnel at a rate of 5 mL/min. During the dropwise addition, the internal temperature of the reaction solution was increased from 20.1°C to 26.1°C. The reaction was typically completed after 4 h (monitored by LC/MS). Upon completion of the reaction, the reaction solution was cooled to 0°C and diluted with methyl ethyl ketone (50 mL). Water (50 mL) was added and the pH was adjusted to 6 with 2.5 N aqueous sodium hydroxide (28 mL). a yellow precipitate was collected by diafiltration and washed with isopropanol and water (1:1, 50 mL). The solid was transferred to a 100 mL round bottom flask and slurried in isopropanol and water (9:1, 50 mL). The slurry was heated to 65.1 °C and maintained for 8 h, followed by cooling to room temperature over 16 h. The slurry was then removed from the flask. An off-white precipitate was collected by filtration and washed with isopropanol (10 mL). The product was dried under high vacuum to constant weight to afford 2-(pyridin-2-yl)-N-(5-(5-(4-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridazin-3-yl)butyl)-1,3,4-thiadiazol-2-yl)acetamide (CB-839) in a yield of 5.27 g (76%).1H NMR (300 MHz, DMSO-d6) δ 12.67 (s, 1H), 11.32 (s, 1H), 8.53-8.49 (m, 1H), 8.22-8.19 (d, J=9.12Hz, 1H), 7.78-7.76 (t, 1H), 7.58-7.26 (m, 7H), 4.01 (s, 2H), 3.87 (s, 2H), 3.01 (bs, 2H) , 2.90 (bs, 2H), 1.73 (bs, 4H).The XRD pattern (form B) of the free base of CB-839 is shown in Fig. 2, with characteristic peaks located at 2θ values of 3.64; 7.32; 7.92; 8.53; 9.30; 9.38; 11.02; 11.98; 14.70; 15.54; 15.87; 16.50 16.59; 18.06; 18.39; 19.10; 20.06; 20.12; 20.61; 21.37; 21.89; 22.41; 22.74; 23.72; 24.10; 24.65; 25.14; 25.78; 26.49; 27.32; 27.55; 28.26; 29.88. 31.20; 31.80; 31.52; 32.80; 34.30; 35.20; 36.41; 38.53; 40.08; 40.94; and 43.86.
in vivo
Telaglenastat (CB-839) (200 mg/kg; p.o.; twice daily for 28 days) has antitumor activity in xenograft models of TNBC[1].
| Animal Model: | Female nu/nu mice with age 4–6 weeks (TNBC patient-derived xenograft model)[1] |
| Dosage: | 200 mg/kg |
| Administration: | Oral administration; twice daily for 28 days |
| Result: | Suppressed tumor growth by 61% relative to vehicle control at the end of study. |
storage
Store at -20°C
References
[1] MATT I GROSS. Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer.[J]. Molecular Cancer Therapeutics, 2014, 13 4: 890-901. DOI:10.1158/1535-7163.mct-13-0870
[2] NATHALIE JACQUE. Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition.[J]. Blood, 2015, 126 11: 1346-1356. DOI:10.1182/blood-2015-01-621870
[3] H FURKAN ALKAN. Cytosolic Aspartate Availability Determines Cell Survival When Glutamine Is Limiting.[J]. Cell metabolism, 2018, 28 5: 706-720.e6. DOI:10.1016/j.cmet.2018.07.021
CB-839 Preparation Products And Raw materials
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View Lastest Price from CB-839 manufacturers
- Product
- CB-839 1439399-58-2
- Price
- US $0.00-0.00/KG
- Min. Order
- 1KG
- Purity
- 98%
- Supply Ability
- 1Ton
- Release date
- 2022-10-13