1439399-58-2 Usage
Description
Different sources of media describe the Description of 1439399-58-2 differently. You can refer to the following data:
1. CB-839 is a potent, selective, and orally bioavailable glutaminase inhibitor with IC50 of 24 nM for recombinant human GAC. Phase 1.
2. 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
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%.
Uses
CB-839 performs an antileukemic activity. It Inhibits GLS1 genes and reduces oxidative phosphorylation leading to leukamic cell proliferation arrest and apoptosis.
References
1) Gross?et al. (2014),?Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer; Mol. Cancer Ther.,13?890
2) Jacque?et al. (2015),?Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition; Blood,?126?1346
3) Alkan?et al.?(2018)?Cytosolic Aspartate Availability Determines Cell Survival When Glutamine is Limiting; Cell Metabolism?28?1
Check Digit Verification of cas no
The CAS Registry Mumber 1439399-58-2 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,3,9,3,9 and 9 respectively; the second part has 2 digits, 5 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 1439399-58:
(9*1)+(8*4)+(7*3)+(6*9)+(5*3)+(4*9)+(3*9)+(2*5)+(1*8)=212
212 % 10 = 2
So 1439399-58-2 is a valid CAS Registry Number.
1439399-58-2Relevant articles and documents
CRYSTAL FORMS OF GLUTAMINASE INHIBITORS
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Page/Page column 41; 42, (2016/04/26)
The invention relates to crystalline salts of a compound having the structure of formula (I), methods for their preparation, and related pharmaceutical compositions comprising the crystalline salt. The invention further relates to methods of treating or preventing cancer or an immunological or neurological disease comprising administering a crystalline salt of the invention.
