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Compound Detail

CHEMBL5095099

EXARAFENIB
🧪 Phase II
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🧪 Phase II
Cc1ccc(NC(=O)N2CC[C@@H](CC(F)(F)F)C2)cc1-c1cc(N[C@H](C)CO)nc(N2CCOCC2)c1

Basic Information

ChEMBL ID CHEMBL5095099
Name EXARAFENIB
Phase Phase II
Structure Type MOL
InChI Key GZMYLSJUNSCMTD-MOPGFXCFSA-N

Known Names

Exarafenib KIN-2787 FREE BASE
5
Targets
16
Activities
2
Assay Types
17
PK Parameters
10
Publications
2
Known Names
1
Indications

Molecular Properties

521.6
MW (Da)
4.49
ALogP
6
HBA
3
HBD
90.0
PSA (Ų)
0.50
QED
1
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer
USAN Stem -rafenib

Extended Properties

Molecular Formula C26H34F3N5O3
MW 521.58
Aromatic Rings 2
Heavy Atoms 37
NP-Likeness -1.58

Indications

Neoplasms

Activity Summary

EC50 12 meas. best 8.1
IC50 4 meas. best 8.85

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
RAF proto-oncogene serine/threonine-protein kinase
CHEMBL1906
IC50 8.85 8.85 1.4 1
Serine/threonine-protein kinase A-Raf
CHEMBL1169596
IC50 8.62 8.62 2.4 1
Serine/threonine-protein kinase B-raf
CHEMBL5145
IC50 8.46 8.46 3.5 1
Unchecked
CHEMBL612545
EC50 8.1 7.02 8.0 12
Epithelial discoidin domain-containing receptor 1
CHEMBL5319
IC50 6.97 6.97 107.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 8710.39 ng.hr.mL-1 Mus musculus
AUC 7823.7 ng.hr.mL-1 Rattus norvegicus
AUC 16168.98 ng.hr.mL-1 Canis lupus familiaris
CL 8.5 mL.min-1.kg-1 Mus musculus
CL 17.4 mL.min-1.kg-1 Rattus norvegicus
CL 11.7 mL.min-1.kg-1 Canis lupus familiaris
Cmax 7000.0 nM Mus musculus
Cmax 1400.0 nM Rattus norvegicus
Cmax 4800.0 nM Canis lupus familiaris
F 44.0 % Mus musculus
F 82.0 % Rattus norvegicus
F 96.0 % Canis lupus familiaris
Fu 0.067 - Homo sapiens
Fu 0.047 - Canis lupus familiaris
Fu 0.063 - Rattus norvegicus
Fu 0.034 - Mus musculus
T1/2 8.0 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
RAF proto-oncogene serine/threonine-protein kinase IC50 = 1.4 nM 8.85 Inhibition of CRAF (unknown origin) by ADP-Glo assay 38230963
Serine/threonine-protein kinase A-Raf IC50 = 2.4 nM 8.62 Inhibition of ARAF (unknown origin) by ADP-Glo assay 38230963
Serine/threonine-protein kinase B-raf IC50 = 3.5 nM 8.46 Inhibition of N-terminal GST fused wild type human BRAF (433 to 726 residues) ex... 38230963
Unchecked EC50 = 8.0 nM 8.1 Inhibition of ERK phosphorylation in human NCI-H2405 cells harboring class-II BR... 38230963
Unchecked EC50 = 8.0 nM 8.1 Inhibition of ERK phosphorylation in human WM3629 cells harboring class-III BRAF... 38230963
Unchecked EC50 = 18.0 nM 7.75 Inhibition of ERK phosphorylation in human CAL-12T cells harboring class-III BRA... 38230963
Unchecked EC50 = 26.0 nM 7.58 Inhibition of ERK phosphorylation in human OV-90 cells harboring class-II BRAF L... 38230963
Unchecked EC50 = 51.0 nM 7.29 Inhibition of ERK phosphorylation in human BXPC-3 cells harboring class-II BRAF ... 38230963
Unchecked EC50 = 62.0 nM 7.21 Inhibition of ERK phosphorylation in human A-375 cells harboring class-I BRAF mu... 38230963
Unchecked EC50 = 103.0 nM 6.99 Inhibition of ERK phosphorylation in human COLO-800 cells harboring class-I BRAF... 38230963
Epithelial discoidin domain-containing receptor 1 IC50 = 107.0 nM 6.97 Inhibition of wild type DDR1 (unknown origin) at in presence of ATP by hotspot k... 38230963
Unchecked EC50 = 144.0 nM 6.84 Inhibition of ERK phosphorylation in human SK-MEL-2 cells harboring wild type BR... 38230963
Unchecked EC50 = 265.0 nM 6.58 Inhibition of ERK phosphorylation in human IPC-298 cells harboring wild type BRA... 38230963
Unchecked EC50 = 351.0 nM 6.46 Inhibition of ERK phosphorylation in human NCI-H358 cells harboring wild type BR... 38230963
Unchecked EC50 = 580.0 nM 6.24 Inhibition of ERK phosphorylation in human CHL-1 cells harboring wild type BRAF ... 38230963
Unchecked EC50 = 7963.0 nM 5.1 Inhibition of ERK phosphorylation in wild type human BJ cells incubated for 1 hr... 38230963

Literature References

PubMed DOI Target Context # Activities
38230963 10.1021/acs.jmedchem.3c01830 ADMET 30
38230963 10.1021/acs.jmedchem.3c01830 Unchecked 21
38230963 10.1021/acs.jmedchem.3c01830 No relevant target 5
38230963 10.1021/acs.jmedchem.3c01830 BXPC-3 4
38230963 10.1021/acs.jmedchem.3c01830 A-375 3
38230963 10.1021/acs.jmedchem.3c01830 SK-MEL-2 3
38230963 10.1021/acs.jmedchem.3c01830 Serine/threonine-protein kinase B-raf 1
38230963 10.1021/acs.jmedchem.3c01830 Serine/threonine-protein kinase A-Raf 1
38230963 10.1021/acs.jmedchem.3c01830 RAF proto-oncogene serine/threonine-protein kinase 1
38230963 10.1021/acs.jmedchem.3c01830 Epithelial discoidin domain-containing receptor 1 1

Data from ChEMBL 36 via Core Engine