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Compound Detail

CHEMBL5189739

BEROTRALSTAT
💊 Approved Drug
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💊 Approved Drug
N#Cc1cccc([C@@H](NCC2CC2)c2ccc(F)c(NC(=O)c3cc(C(F)(F)F)nn3-c3cccc(CN)c3)c2)c1

Basic Information

ChEMBL ID CHEMBL5189739
Name BEROTRALSTAT
Phase Approved
Structure Type MOL
InChI Key UXNXMBYCBRBRFD-MUUNZHRXSA-N
Therapeutic ✓ Yes

Known Names

BCX-7353 Bcx7353 Berotralstat
3
Targets
16
Activities
2
Assay Types
24
PK Parameters
13
Publications
3
Known Names
2
Indications

Molecular Properties

562.6
MW (Da)
5.70
ALogP
6
HBA
3
HBD
108.8
PSA (Ų)
0.23
QED
2
Ro5 Violations
9
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2020
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral
USAN Stem -stat
USAN Year 2019

Extended Properties

Molecular Formula C30H26F4N6O
MW 562.57
Aromatic Rings 4
Heavy Atoms 41
NP-Likeness -1.71

Indications

Angioedemas, Hereditary Angioedema

ATC Classification

B06AC06
berotralstat
Level 1: BLOOD AND BLOOD FORMING ORGANS
Level 2: OTHER HEMATOLOGICAL AGENTS

Activity Summary

IC50 9 meas. best 9.06
Ki 7 meas. best 9.36

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Plasma kallikrein
CHEMBL2000
Ki 9.36 7.8514 0.4 7
Plasma kallikrein
CHEMBL2000
IC50 9.06 8.2957 0.9 7
Plasminogen
CHEMBL1801
IC50 5.4 5.4 3967.0 1
Trypsin
CHEMBL2095204
IC50 4.96 4.96 11000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 2210.0 ng.hr.mL-1 Rattus norvegicus
AUC 1621.0 ng.hr.mL-1 Rattus norvegicus
AUC 4779.0 ng.hr.mL-1 Rattus norvegicus
AUC 1858.0 ng.hr.mL-1 Rattus norvegicus
AUC 6179.0 ng.hr.mL-1 Rattus norvegicus
AUC 974.0 ng.hr.mL-1 Macaca mulatta
AUC 4154.0 ng.hr.mL-1 Macaca mulatta
CL 27.0 mL.min-1.kg-1 Rattus norvegicus
CL 81.0 mL.min-1.kg-1 Rattus norvegicus
CL 30.0 mL.min-1.kg-1 Macaca mulatta
CL 73.0 mL.min-1.kg-1 Macaca mulatta
Cmax 0.242 ug.mL-1 Rattus norvegicus
Cmax 0.773 ug.mL-1 Rattus norvegicus
Cmax 0.475 ug.mL-1 Rattus norvegicus
Cmax 0.673 ug.mL-1 Macaca mulatta
Cmax 0.342 ug.mL-1 Macaca mulatta
F 33.0 % Rattus norvegicus
F 45.0 % Macaca mulatta
T1/2 10.1 hr Rattus norvegicus
T1/2 18.5 hr Rattus norvegicus
T1/2 18.3 hr Macaca mulatta
T1/2 22.7 hr Macaca mulatta
Tmax 2.0 hr Rattus norvegicus
Tmax 4.7 hr Macaca mulatta

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Plasma kallikrein Ki = 0.44 nM 9.36 Inhibition of purified human plasma kallikrein assessed as inhibition constant u... 34436898
Plasma kallikrein IC50 = 0.88 nM 9.06 Inhibition of purified human plasma kallikrein using H-D-Pro-Phe-Arg-pNA.2HCl as... 34436898
Plasma kallikrein IC50 = 1.0 nM 9.0 Inhibition of plasma kallikrein (unknown origin) 36439976
Plasma kallikrein IC50 = 1.8 nM 8.74 Inhibition of purified human plasma kallikrein using H-D-Pro-Phe-Arg-pNA.2HCl as... 34436898
Plasma kallikrein IC50 = 5.8 nM 8.24 Inhibition of endogenous human plasma kallikrein using Z-Phe-Arg-AMC.HCl as subs... 34436898
Plasma kallikrein IC50 = 13.9 nM 7.86 Inhibition of purified human plasma kallikrein using H-D-Pro-Phe-Arg-pNA.2HCl as... 34436898
Plasma kallikrein IC50 = 14.0 nM 7.85 Inhibition of endogenous human plasma kallikrein using Z-Phe-Arg-AMC.HCl as subs... 34436898
Plasma kallikrein Ki = 25.1 nM 7.6 Plasma Kallikrein Activity Assay: The effect of compounds of the invention on hu... -
Plasma kallikrein Ki = 25.1 nM 7.6 Plasma Kallikrein Activity Assay: The effect of compounds of the invention on hu... -
Plasma kallikrein Ki = 25.1 nM 7.6 Plasma Kallikrein Activity Assay: The effect of compounds of the invention on hu... -
Plasma kallikrein Ki = 25.1 nM 7.6 Plasma Kallikrein Activity Assay: Plasma kallikrein activity assay. The effect o... -
Plasma kallikrein Ki = 25.1 nM 7.6 Plasma Kallikrein Activity Assay: Plasma kallikrein activity assay. The effect o... -
Plasma kallikrein Ki = 25.1 nM 7.6 Plasma Kallikrein Activity Assay: Plasma kallikrein activity assay. The effect o... -
Plasma kallikrein IC50 = 48.1 nM 7.32 Inhibition of endogenous human plasma kallikrein using Z-Phe-Arg-AMC.HCl as subs... 34436898
Plasminogen IC50 = 3967.0 nM 5.4 Inhibition of human plasmin using Z-Lys-SBzl as substrate measured immediately b... 34436898
Trypsin IC50 = 11000.0 nM 4.96 Inhibition of human trypsin using Nalpha-Benzoyl-L-Arginine p-nitroaniline as su... 34436898

Literature References

PubMed DOI Target Context # Activities
34436898 10.1021/acs.jmedchem.1c00511 ADMET 25
34436898 10.1021/acs.jmedchem.1c00511 Unchecked 9
34436898 10.1021/acs.jmedchem.1c00511 Plasma kallikrein 8
34436898 10.1021/acs.jmedchem.1c00511 No relevant target 2
34436898 10.1021/acs.jmedchem.1c00511 Trypsin 1
34436898 10.1021/acs.jmedchem.1c00511 Prothrombin 1
34436898 10.1021/acs.jmedchem.1c00511 Plasminogen 1
34436898 10.1021/acs.jmedchem.1c00511 Tissue-type plasminogen activator 1
34436898 10.1021/acs.jmedchem.1c00511 Adenomatous polyposis coli protein 1
34436898 10.1021/acs.jmedchem.1c00511 Complement C1s subcomponent 1
34436898 10.1021/acs.jmedchem.1c00511 Coagulation factor X 1
34436898 10.1021/acs.jmedchem.1c00511 Coagulation factor XII 1
36439976 10.1039/d2md00206j Plasma kallikrein 1

Data from ChEMBL 36 via Core Engine