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Compound Detail

CHEMBL3639788

TELAGLENASTAT
🧪 Phase II
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🧪 Phase II
O=C(Cc1cccc(OC(F)(F)F)c1)Nc1ccc(CCCCc2nnc(NC(=O)Cc3ccccn3)s2)nn1

Basic Information

ChEMBL ID CHEMBL3639788
Name TELAGLENASTAT
Phase Phase II
Structure Type MOL
InChI Key PRAAPINBUWJLGA-UHFFFAOYSA-N

Known Names

CB-839 Telaglenastat
15
Targets
60
Activities
3
Assay Types
26
PK Parameters
20
Publications
2
Known Names
14
Indications
1
Mechanisms

Molecular Properties

571.6
MW (Da)
4.55
ALogP
9
HBA
2
HBD
131.9
PSA (Ų)
0.24
QED
1
Ro5 Violations
12
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral
USAN Stem -stat
USAN Year 2019

Extended Properties

Molecular Formula C26H24F3N7O3S
MW 571.59
Aromatic Rings 4
Heavy Atoms 40
NP-Likeness -1.87

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Glutaminase kidney isoform, mitochondrial inhibitor INHIBITOR Glutaminase kidney isoform, mitochondrial

Indications

Carcinoma, Non-Small-Cell Lung Carcinoma, Renal Cell Carcinoma, Renal Cell Neurilemmoma Prostatic Neoplasms, Castration-Resistant Triple Negative Breast Neoplasms Uterine Cervical Neoplasms Uterine Cervical Neoplasms Astrocytoma Leukemia, Myeloid, Acute Multiple Myeloma Myelodysplastic Syndromes Neoplasms Precursor Cell Lymphoblastic Leukemia-Lymphoma

Activity Summary

IC50 55 meas. best 9.7
Kd 4 meas. best 7.04
EC50 1 meas. best 7.78

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Unchecked
CHEMBL612545
IC50 9.7 8.0933 0.2 6
Glutaminase kidney isoform, mitochondrial
CHEMBL2146302
IC50 8.7 7.5946 2.0 24
A549
CHEMBL392
IC50 8.22 7.666 6.0 5
Unchecked
CHEMBL612545
EC50 7.78 7.78 16.4 1
Glutaminase kidney isoform, mitochondrial
CHEMBL4523110
IC50 7.7 7.7 20.0 2
HCT-116
CHEMBL394
IC50 7.55 7.04 28.0 5
MDA-MB-231
CHEMBL400
IC50 7.48 7.39 33.0 2
NCI-H460
CHEMBL396
IC50 7.44 7.44 36.0 1
CAKI-1
CHEMBL614067
IC50 7.4 7.4 40.0 1
Glutaminase kidney isoform, mitochondrial
CHEMBL2146302
Kd 7.04 6.7025 92.0 4
HCC1806
CHEMBL1075457
IC50 7.0 7.0 100.0 1
MDA-MB-436
CHEMBL4296465
IC50 6.39 6.3467 410.0 3
CT26
CHEMBL613866
IC50 6.38 6.38 420.0 1
H22
CHEMBL614998
IC50 5.87 5.87 1340.0 1
SW1990
CHEMBL1075592
IC50 4.88 4.88 13060.0 1
HT-1080
CHEMBL614580
IC50 4.35 4.35 44380.0 1
HCC827
CHEMBL4296422
IC50 4.29 4.29 51420.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 2379.0 ng.hr.mL-1 Rattus norvegicus
AUC 18862.0 ng.hr.mL-1 Rattus norvegicus
AUC 2431.0 ng.hr.mL-1 Rattus norvegicus
AUC 18928.0 ng.hr.mL-1 Rattus norvegicus
CL 15.0 mL.min-1.g-1 Homo sapiens
CL 14.0 mL.min-1.kg-1 Rattus norvegicus
CL 9.7 mL.min-1.g-1 Homo sapiens
CL 12.3 mL.min-1.g-1 Mus musculus
CL 135.0 mL.min-1.kg-1 Rattus norvegicus
CL 186.67 mL.min-1.kg-1 Rattus norvegicus
CL 19.5 mL.min-1.g-1 Homo sapiens
CL 35.0 mL.min-1.g-1 Homo sapiens
Cmax 3002.15 nM Rattus norvegicus
Cmax 3010.0 nM Mus musculus
F 32.0 % Rattus norvegicus
F 19.0 % Rattus norvegicus
Fu 0.009 - Homo sapiens
Fu 0.1029 - Mus musculus
T1/2 1.4 hr Homo sapiens
T1/2 1.05 hr Mus musculus
T1/2 3.7 hr Rattus norvegicus
T1/2 3.2 hr Rattus norvegicus
T1/2 1.524 hr Homo sapiens
T1/2 1.65 hr Homo sapiens
Vd 26.1 L.kg-1 Rattus norvegicus
Vd 60.9 L.kg-1 Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Unchecked IC50 = 0.2 nM 9.7 Inhibition of GLS in human PC3 cells using glutamine as substrate measured after... 31199640
Glutaminase kidney isoform, mitochondrial IC50 = 2.0 nM 8.7 Inhibition of human KGA preincubated for 15 to 30 mins followed by substrate add... 30543285
Unchecked IC50 = 2.0 nM 8.7 Antiproliferative activity against human MDA-MB-231met2 cells 30148361
Glutaminase kidney isoform, mitochondrial IC50 = 2.0 nM 8.7 Negative allosteric modulator activity at human wildtype KGA incubated for 5 hrs... 37465295
Glutaminase kidney isoform, mitochondrial IC50 = 5.0 nM 8.3 Enzyme Assay-Time Dependence: Compounds were assessed for their ability to inhib... -
Glutaminase kidney isoform, mitochondrial IC50 = 5.0 nM 8.3 Inhibition of GAC (unknown origin) assessed as NADH formation using 10 mM glutam... 29969024
Glutaminase kidney isoform, mitochondrial IC50 = 5.0 nM 8.3 Inhibition of GAC (unknown origin) 30522056
Glutaminase kidney isoform, mitochondrial IC50 = 5.0 nM 8.3 Recombinant Enzyme Assay: Compounds were assessed for their ability to inhibit t... -
Unchecked IC50 = 5.0 nM 8.3 Recombinant Enzyme Assay - Time Dependence: Compounds were assessed for their ab... -
A549 IC50 = 6.0 nM 8.22 Antiproliferative activity against human A549 cells assessed as reduction in cel... 33118821
Glutaminase kidney isoform, mitochondrial IC50 = 6.0 nM 8.22 Inhibition of recombinant human GLS1 using glutamine as substrate preincubated f... 33118821
Glutaminase kidney isoform, mitochondrial IC50 = 7.0 nM 8.15 Inhibition of recombinant 6His-tagged GLS1 KGA isoform (unknown origin) (63 to 6... 31199640
Unchecked EC50 = 16.44 nM 7.78 Inhibition of human recombinant GAC K320A mutant (73 to 598 residues ) expressed... 37849538
Glutaminase kidney isoform, mitochondrial IC50 = 17.0 nM 7.77 Negative allosteric modulator activity at human wildtype KGA using glutamine as ... 37465295
A549 IC50 = 18.78 nM 7.73 Antiproliferative activity against human A549 cells assessed as reduction in cel... 37849538
Glutaminase kidney isoform, mitochondrial IC50 = 20.0 nM 7.7 Inhibition of GLS1 (unknown origin) 33792311
Glutaminase kidney isoform, mitochondrial IC50 = 20.0 nM 7.7 Inhibition of human recombinant GLS1 36996714
Glutaminase kidney isoform, mitochondrial IC50 = 20.0 nM 7.7 Inhibition of GLS1 in mouse brain assessed as inhibition of glutamate production... 35428013
Glutaminase kidney isoform, mitochondrial IC50 = 20.0 nM 7.7 Inhibition of GLS1 in mouse kidney assessed as inhibition of glutamate productio... 35428013
Unchecked IC50 = 20.0 nM 7.7 Inhibition of GAC (unknown origin) 30148361

Literature References

PubMed DOI Target Context # Activities
33792311 10.1021/acs.jmedchem.0c02044 ADMET 24
35428013 10.1016/j.ejmech.2022.114337 Glutaminase kidney isoform, mitochondrial 16
36525694 10.1016/j.ejmech.2022.115014 ADMET 9
31199640 10.1021/acs.jmedchem.9b00260 ADMET 7
31603674 10.1021/acs.jmedchem.9b01035 Glutaminase kidney isoform, mitochondrial 6
30543285 10.1021/acs.jmedchem.8b01198 HCT-116 5
35428013 10.1016/j.ejmech.2022.114337 ADMET 5
33792311 10.1021/acs.jmedchem.0c02044 Glutaminase kidney isoform, mitochondrial 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
30543285 10.1021/acs.jmedchem.8b01198 H22 4
30543285 10.1021/acs.jmedchem.8b01198 ADMET 4
36038117 10.1016/j.bmcl.2022.128956 Glutaminase kidney isoform, mitochondrial 3
36525694 10.1016/j.ejmech.2022.115014 Glutaminase kidney isoform, mitochondrial 3
30543285 10.1021/acs.jmedchem.8b01198 A549 3
37465295 10.1021/acsmedchemlett.2c00470 Unchecked 3
30148361 10.1021/acs.jmedchem.8b00961 Unchecked 3
36655131 10.1021/acsmedchemlett.2c00302 HCT-116 3
37465295 10.1021/acsmedchemlett.2c00470 Glutaminase kidney isoform, mitochondrial 3
31603674 10.1021/acs.jmedchem.9b01035 HCT-116 2
37849538 10.1021/acsmedchemlett.3c00375 A549 2

Data from ChEMBL 36 via Core Engine