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Compound Detail

CHEMBL227875

PRETOMANID
💊 Approved Drug
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💊 Approved Drug
O=[N+]([O-])c1cn2c(n1)OC[C@@H](OCc1ccc(OC(F)(F)F)cc1)C2

Basic Information

ChEMBL ID CHEMBL227875
Name PRETOMANID
Phase Approved
Structure Type MOL
InChI Key ZLHZLMOSPGACSZ-NSHDSACASA-N
Therapeutic ✓ Yes

Known Names

Dovprela (previously pretomanid fgk) PA 824 PA-824 PA824 Pretomanid
8
Targets
16
Activities
2
Assay Types
30
PK Parameters
20
Publications
5
Known Names
4
Indications
1
Mechanisms

Molecular Properties

359.3
MW (Da)
2.67
ALogP
7
HBA
0
HBD
88.7
PSA (Ų)
0.60
QED
0
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2019
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

First in Class
USAN Stem -manid
USAN Year 2014

Extended Properties

Molecular Formula C14H12F3N3O5
MW 359.26
Aromatic Rings 2
Heavy Atoms 25
NP-Likeness -0.63

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Unknown - -

Indications

Tuberculosis Tuberculosis, Multidrug-Resistant Tuberculosis, Multidrug-Resistant Tuberculosis, Pulmonary

ATC Classification

J04AK08
pretomanid
Level 1: ANTIINFECTIVES FOR SYSTEMIC USE
Level 2: ANTIMYCOBACTERIALS

Activity Summary

IC50 13 meas. best 6.4
EC50 3 meas. best 4.52

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Mycobacterium tuberculosis
CHEMBL360
IC50 6.4 6.225 400.0 2
Giardia intestinalis
CHEMBL612652
IC50 5.52 5.5133 3000.0 3
Leishmania donovani
CHEMBL367
IC50 5.41 5.41 3900.0 1
Entamoeba histolytica
CHEMBL612853
IC50 5.03 5.02 9300.0 3
Trypanosoma cruzi
CHEMBL368
IC50 5.0 5.0 10000.0 1
Trypanosoma brucei brucei
CHEMBL612851
IC50 4.72 4.71 19000.0 2
Trypanosoma brucei
CHEMBL612849
EC50 4.52 4.4833 30500.0 3
Leishmania infantum
CHEMBL612848
IC50 4.23 4.23 59000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 26540.0 ng.hr.mL-1 Cavia porcellus
AUC 25770.0 ng.hr.mL-1 Cavia porcellus
AUC 14800.0 ng.hr.mL-1 Cavia porcellus
AUC 32340.0 ng.hr.mL-1 Cavia porcellus
AUC 50960.0 ng.hr.mL-1 Cavia porcellus
AUC 70400.0 ng.hr.mL-1 Mus musculus
AUC 7500.0 ng.hr.mL-1 Homo sapiens
AUC - - Mus musculus
AUC 50900.0 ng.hr.mL-1 Mus musculus
CL 12.1 mL.min-1.kg-1 Mus musculus
CL 25.0 mL.min-1.g-1 Homo sapiens
CL 12.1 mL.min-1.kg-1 Mus musculus
Cmax 25580.36 nM Cavia porcellus
Cmax 11523.69 nM Cavia porcellus
Cmax 5594.83 nM Cavia porcellus
Cmax 9519.57 nM Cavia porcellus
Cmax 12748.43 nM Cavia porcellus
Cmax 10577.3 nM Mus musculus
Cmax 835.05 nM Homo sapiens
Cmax 16701.0 nM Mus musculus
F 0.56 % Cavia porcellus
F 0.59 % Cavia porcellus
F 2.11 % Cavia porcellus
F 0.63 % Cavia porcellus
F 1.12 % Cavia porcellus
F 0.62 % Cavia porcellus
F 0.74 % Cavia porcellus
F 100.0 % Mus musculus
MRT 2.69 hr Cavia porcellus
MRT 5.37 hr Cavia porcellus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Mycobacterium tuberculosis IC50 = 400.0 nM 6.4 Antimycobacterial activity against Mycobacterium tuberculosis H37Rv expressing L... 25818768
Mycobacterium tuberculosis IC50 = 900.0 nM 6.05 Anti-tubercular activity against Mycobacterium tuberculosis 26199118
Giardia intestinalis IC50 = 3000.0 nM 5.52 Antiparasitic activity against Giardia lamblia WB trophozoites after 24 to 48 hr... 30468386
Giardia intestinalis IC50 = 3000.0 nM 5.52 Antiparasitic activity against Giardia lamblia P15 WB assessed a inhibition of p... 33151678
Giardia intestinalis IC50 = 3162.28 nM 5.5 Antiparasitic activity against Giardia lamblia WB trophozoites after 24 to 48 hr... 30468386
Leishmania donovani IC50 = 3900.0 nM 5.41 Antileishmanial activity against Leishmania donovani amastigotes expressing Luc ... 29461823
Entamoeba histolytica IC50 = 9300.0 nM 5.03 Antiparasitic activity against Entamoeba histolytica HM-1:IMSS trophozoites afte... 30468386
Entamoeba histolytica IC50 = 9300.0 nM 5.03 Antiparasitic activity against Entamoeba histolytica HM1:1MSS assessed as parasi... 33151678
Trypanosoma cruzi IC50 = 10000.0 nM 5.0 Antitrypanosomal activity against Trypanosoma cruzi infected in human MRC5 cells... 29461823
Entamoeba histolytica IC50 = 10000.0 nM 5.0 Antiparasitic activity against Entamoeba histolytica HM-1:IMSS trophozoites afte... 30468386
Trypanosoma brucei brucei IC50 = 19000.0 nM 4.72 Antiparasitic activity against bloodstream form of Trypanosoma brucei brucei str... 30468386
Trypanosoma brucei brucei IC50 = 19952.62 nM 4.7 Antiparasitic activity against bloodstream form of Trypanosoma brucei brucei str... 30468386
Trypanosoma brucei EC50 = 30500.0 nM 4.52 Antimicrobial activity against Trypanosoma brucei NfxR1 20439607
Trypanosoma brucei EC50 = 30800.0 nM 4.51 Antimicrobial activity against Trypanosoma brucei NfxR2 20439607
Trypanosoma brucei EC50 = 37800.0 nM 4.42 Antimicrobial activity against Trypanosoma brucei 20439607
Leishmania infantum IC50 = 59000.0 nM 4.23 Antileishmanial activity against Leishmania infantum amastigotes infected in mou... 29461823

Literature References

PubMed DOI Target Context # Activities
20937781 10.1128/aac.00849-10 Mycobacterium tuberculosis 55
19139288 10.1128/aac.01389-08 Cavia porcellus 37
10879539 10.1038/35016103 Mycobacterium tuberculosis 37
- 10.6019/CHEMBL3832761 Mycobacterium tuberculosis 15
36111399 10.1021/acs.jmedchem.2c00972 ADMET 14
17132069 10.1371/journal.pmed.0030466 Mycobacterium tuberculosis 12
30468386 10.1021/acs.jmedchem.8b01578 ADMET 10
38157261 10.1021/acs.jmedchem.3c00925 Mycobacterium tuberculosis 9
23930153 10.1021/ml400088y Mycobacterium tuberculosis 8
18625764 10.1128/aac.00379-08 Mycobacterium tuberculosis 8
19039139 10.1126/science.1164571 Mycobacterium tuberculosis 7
22391032 10.1016/j.bmc.2012.02.025 Mycobacterium tuberculosis 7
24087924 10.1021/np400497f Mycobacterium tuberculosis 7
19564371 10.1128/aac.00550-09 Mycobacterium tuberculosis 6
33151678 10.1021/acs.jmedchem.0c01372 ADMET 6
22148391 10.1021/jm2012276 Mycobacterium tuberculosis 6
22421275 10.1016/j.ejmech.2012.02.033 Mycobacterium tuberculosis 6
19139288 10.1128/aac.01389-08 No relevant target 5
19209889 10.1021/jm801246z Mycobacterium tuberculosis 5
23910985 10.1016/j.bmcl.2013.07.006 NON-PROTEIN TARGET 5

Data from ChEMBL 36 via Core Engine