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Compound Detail

CHEMBL3947537

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Cc1cc([C@H](C)Nc2nccc(N3C(=O)OC[C@@H]3[C@H](C)F)n2)ncc1-c1ccnc(C(F)(F)F)c1

Basic Information

ChEMBL ID CHEMBL3947537
Phase Preclinical
Structure Type MOL
InChI Key DCGDPJCUIKLTDU-SUNYJGFJSA-N
4
Targets
35
Activities
1
Assay Types
18
PK Parameters
18
Publications
0
Known Names

Molecular Properties

490.5
MW (Da)
5.12
ALogP
7
HBA
1
HBD
93.1
PSA (Ų)
0.48
QED
1
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C23H22F4N6O2
MW 490.46
Aromatic Rings 3
Heavy Atoms 35
NP-Likeness -0.79

Activity Summary

IC50 35 meas. best 7.96

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Isocitrate dehydrogenase [NADP] cytoplasmic
CHEMBL2007625
IC50 7.96 7.2071 11.0 21
HCT-116
CHEMBL394
IC50 7.62 7.61 24.0 2
U-87 MG
CHEMBL614247
IC50 6.44 5.7713 360.0 8
Isocitrate dehydrogenase [NADP], mitochondrial
CHEMBL3991501
IC50 5.42 5.21 3800.0 4

Pharmacokinetic Data

Parameter Value Units Species
AUC 35264.07 ng.hr.mL-1 Mus musculus
AUC 103977.52 ng.hr.mL-1 Mus musculus
AUC 2648.48 ng.hr.mL-1 Mus musculus
AUC 9416.83 ng.hr.mL-1 Mus musculus
AUC 43601.89 ng.hr.mL-1 Mus musculus
AUC 4953.65 ng.hr.mL-1 Mus musculus
AUC 73078.54 ng.hr.mL-1 Mus musculus
AUC 2697.53 ng.hr.mL-1 Rattus norvegicus
AUC 1667.56 ng.hr.mL-1 Rattus norvegicus
AUC 3040.85 ng.hr.mL-1 Rattus norvegicus
CL 56.0 mL.min-1.g-1 Homo sapiens
CL 28.0 mL.min-1.g-1 Canis lupus familiaris
CL 45.0 mL.min-1.g-1 Rattus norvegicus
CL 61.0 mL.min-1.g-1 Mus musculus
CL 29.0 mL.min-1.kg-1 Mus musculus
CL 34.0 mL.min-1.kg-1 Rattus norvegicus
CL 24.0 mL.min-1.kg-1 Canis lupus familiaris
Cmax 16200.0 nM Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 11.0 nM 7.96 Mutant IDH1 Biochemical Assay: LC-MS Detection of 2-HG: Mutant IDH1 R132H cataly... -
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 11.0 nM 7.96 LC-MS Detection of 2-HG Assay: The biochemical reactions were performed at room ... -
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 18.0 nM 7.75 Inhibition of IDH1 R132H mutant (unknown origin) using alpha-ketoglutarate as su... 29057061
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 18.0 nM 7.75 Inhibition of IDH1 R132H mutant (unknown origin) 38896992
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 18.0 nM 7.75 Inhibition of human IDH1 R132H mutant 37235998
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 18.0 nM 7.75 Inhibition of IDH1 R132H mutant (unknown origin) by enzymatic assay 37235998
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 20.0 nM 7.7 Inhibition of IDH1 R132H mutant in human MCF10A cells assessed as cell growth in... 29057061
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 24.0 nM 7.62 Inhibition of IDH1 R132H mutant in human HCT116 cells assessed as reduction in 2... 29057061
HCT-116 IC50 = 24.0 nM 7.62 Antiproliferative activity against human HCT-116 cells assessed as reduction in ... 37235998
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 24.0 nM 7.62 Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced fo... -
HCT-116 IC50 = 25.0 nM 7.6 Antiproliferative activity against human HCT-116 cells assessed as reduction in ... 37235998
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 25.5 nM 7.59 Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced fo... -
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 26.0 nM 7.58 Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced fo... -
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 27.0 nM 7.57 Inhibition of IDH1 R132H mutant (unknown origin) assessed as NADPH consumption u... 29057061
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 28.0 nM 7.55 Inhibition of IDH1 R132C mutant (unknown origin) assessed as NADPH consumption u... 29057061
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 42.51 nM 7.37 Inhibition of recombinant IDH1 R132H mutant (unknown origin) using alpha-ketoglu... 38651495
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 50.2 nM 7.3 Inhibition of recombinant human C-terminal His8-tagged IDH1 R132C mutant express... 31561044
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 49.6 nM 7.3 Inhibition of recombinant human C-terminal His8-tagged IDH1 R132H mutant express... 31561044
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 52.7 nM 7.28 Inhibition of IDH1 R132C mutant in human HT1080 cells assessed as reduction in 2... 31561044
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 53.93 nM 7.27 Inhibition of recombinant IDH1 R132C mutant (unknown origin) using alpha-ketoglu... 38651495

Literature References

PubMed DOI Target Context # Activities
29057061 10.1021/acsmedchemlett.7b00342 Mus musculus 26
29057061 10.1021/acsmedchemlett.7b00342 ADMET 18
38651495 10.1021/acs.jmedchem.3c02482 U-87 MG 17
29057061 10.1021/acsmedchemlett.7b00342 Isocitrate dehydrogenase [NADP] cytoplasmic 6
29057061 10.1021/acsmedchemlett.7b00342 Unchecked 5
31561044 10.1016/j.ejmech.2019.111694 Isocitrate dehydrogenase [NADP] cytoplasmic 4
29057061 10.1021/acsmedchemlett.7b00342 No relevant target 3
38651495 10.1021/acs.jmedchem.3c02482 Isocitrate dehydrogenase [NADP] cytoplasmic 3
29057061 10.1021/acsmedchemlett.7b00342 Rattus norvegicus 2
29057061 10.1021/acsmedchemlett.7b00342 Isocitrate dehydrogenase [NADP], mitochondrial 2
38651495 10.1021/acs.jmedchem.3c02482 Unchecked 2
37235998 10.1016/j.ejmech.2023.115464 Isocitrate dehydrogenase [NADP] cytoplasmic 2
37235998 10.1016/j.ejmech.2023.115464 HCT-116 2
37235998 10.1016/j.ejmech.2023.115464 ADMET 2
37235998 10.1016/j.ejmech.2023.115464 Isocitrate dehydrogenase [NADP], mitochondrial 2
29057061 10.1021/acsmedchemlett.7b00342 Canis familiaris 1
29057061 10.1021/acsmedchemlett.7b00342 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 1
38896992 10.1016/j.ejmech.2024.116610 Isocitrate dehydrogenase [NADP] cytoplasmic 1

Data from ChEMBL 36 via Core Engine