1439399-58-2 Usage
Uses
Used in Antileukemic Applications:
CB-839 is used as an antileukemic agent for inhibiting the proliferation of leukemic cells and inducing apoptosis. Its antileukemic activity is achieved through the inhibition of GLS1 genes and the reduction of oxidative phosphorylation, which leads to the arrest of cell proliferation in acute myeloid leukemia.
Used in Triple-Negative Breast Cancer Treatment:
CB-839 is used as an antiproliferative agent in the treatment of triple-negative breast cancer. It has demonstrated an antiproliferative effect in the triple-negative breast cancer cell line, HCC-1806, without activity in the estrogen receptor-positive cell line T47D.
Used in Combination Therapy:
CB-839 is used in combination with Aspartate-glutamate carrier 1 (AGC1) inhibition to synergize and limit tumor growth. This combination therapy aims to enhance the effectiveness of cancer treatment by targeting multiple pathways involved in tumor progression.
Used in Pharmaceutical Industry:
CB-839 is used as a potent and selective inhibitor of glutaminase in the pharmaceutical industry for the development of novel cancer treatments. Its oral bioavailability and selectivity make it a promising candidate for further research and potential clinical applications in oncology.
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%.
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 academic research and scientific papers
CRYSTAL FORMS OF GLUTAMINASE INHIBITORS
-
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.
HETEROCYCLIC INHIBITORS OF GLUTAMINASE
-
, (2013/06/06)
The invention relates to the heterocyclic compounds of Formula (I) as defined further herein, and pharmaceutical preparations thereof. The invention further relates to methods of treating cancer, immunological or neurological diseases using the heterocyclic compounds of the invention.
