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Compound Detail

CHEMBL5279308

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Cc1ncn(CC(=O)N2CCN(c3sc(C(F)(F)F)nc3-c3cnc(C(F)(F)F)nc3)C[C@H]2CCO)n1

Basic Information

ChEMBL ID CHEMBL5279308
Phase Preclinical
Structure Type MOL
InChI Key FDZFVXKCJKOSRC-CYBMUJFWSA-N
5
Targets
16
Activities
2
Assay Types
30
PK Parameters
20
Publications
0
Known Names

Molecular Properties

550.5
MW (Da)
2.64
ALogP
10
HBA
1
HBD
113.2
PSA (Ų)
0.47
QED
1
Ro5 Violations
6
Rot. Bonds

Drug Information

Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C20H20F6N8O2S
MW 550.49
Aromatic Rings 3
Heavy Atoms 37
NP-Likeness -1.15

Activity Summary

IC50 15 meas. best 8.82
Kd 1 meas. best 8.34

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
C-X-C chemokine receptor type 3
CHEMBL5200
IC50 8.82 7.9875 1.5 4
C-X-C chemokine receptor type 3
CHEMBL1075172
IC50 8.66 7.6 2.2 2
C-X-C chemokine receptor type 3
CHEMBL1075194
IC50 8.55 8.475 2.8 2
C-X-C chemokine receptor type 3
CHEMBL4441
IC50 8.49 7.9517 3.2 6
C-X-C chemokine receptor type 3
CHEMBL4441
Kd 8.34 8.34 4.6 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 7.58 7.58 26.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 4210.0 ng.hr.mL-1 Rattus norvegicus
AUC 3910.0 ng.hr.mL-1 Canis lupus familiaris
AUC 3610.0 ng.hr.mL-1 Macaca fascicularis
CL 10.0 mL.min-1.g-1 Homo sapiens
CL 0.04 mL.min-1.g-1 Homo sapiens
CL 0.04 mL.min-1.g-1 Homo sapiens
CL 10.0 mL.min-1.g-1 Rattus norvegicus
CL 10.0 mL.min-1.g-1 Canis lupus familiaris
CL 2.0 mL.min-1.g-1 Homo sapiens
CL 2.0 mL.min-1.g-1 Rattus norvegicus
CL 2.0 mL.min-1.g-1 Canis lupus familiaris
CL 14.0 mL.min-1.kg-1 Rattus norvegicus
CL 156.0 mL.min-1.kg-1 Rattus norvegicus
CL 5.0 mL.min-1.kg-1 Canis lupus familiaris
CL 15.0 mL.min-1.kg-1 Canis lupus familiaris
CL 9.5 mL.min-1.kg-1 Rattus norvegicus
CL 9.5 mL.min-1.kg-1 Canis lupus familiaris
CL 5.3 mL.min-1.kg-1 Macaca fascicularis
Cmax 314.27 nM Mus musculus
Cmax 76.3 nM Mus musculus
Cmax 1015.46 nM Mus musculus
Cmax 1653.07 nM Rattus norvegicus
Cmax 1653.07 nM Canis lupus familiaris
Cmax 1335.17 nM Macaca fascicularis
F 80.0 % Rattus norvegicus
F 89.0 % Canis lupus familiaris
F 92.0 % Macaca fascicularis
Fu 0.23 - Homo sapiens
Fu 0.09 - Rattus norvegicus
Fu 0.34 - Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
C-X-C chemokine receptor type 3 IC50 = 1.5 nM 8.82 Antagonist activity at mouse CXCR3 expressed in CHO-K1 cells assessed as reducti... 36883854
C-X-C chemokine receptor type 3 IC50 = 2.2 nM 8.66 Antagonist activity at rat CXCR3 expressed in CHO-K1 cells assessed as reduction... 36883854
C-X-C chemokine receptor type 3 IC50 = 2.8 nM 8.55 Antagonist activity at dog CXCR3 expressed in CHO-K1 cells assessed as reduction... 36883854
C-X-C chemokine receptor type 3 IC50 = 3.2 nM 8.49 Antagonist activity at human CXCR3 expressed in CHO-K1 cells assessed as reducti... 36883854
C-X-C chemokine receptor type 3 IC50 = 3.3 nM 8.48 Antagonist activity at human CXCR3 expressed in CHO-K1 cells assessed as reducti... 36883854
C-X-C chemokine receptor type 3 IC50 = 4.0 nM 8.4 Antagonist activity at dog CXCR3 expressed in CHO-K1 cells assessed as reduction... 36883854
C-X-C chemokine receptor type 3 IC50 = 4.4 nM 8.36 Antagonist activity at mouse CXCR3 expressed in CHO-K1 cells assessed as reducti... 36883854
C-X-C chemokine receptor type 3 Kd = 4.6 nM 8.34 Binding affinity to human CXCR3 expressed in CHO-K1 cell membrane assessed as di... 36883854
C-X-C chemokine receptor type 3 IC50 = 5.3 nM 8.28 Antagonist activity at human CXCR3 expressed in CHO-K1 cells assessed as reducti... 36883854
C-X-C chemokine receptor type 3 IC50 = 10.5 nM 7.98 Antagonist activity at mouse CXCR3-mediated chemotaxis expressed in CD3/CD28-act... 36883854
C-X-C chemokine receptor type 3 IC50 = 10.9 nM 7.96 Antagonist activity at human CXCR3-mediated chemotaxis expressed in CD3/CD28-act... 36883854
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 26.0 nM 7.58 Inhibition of human ERG stably expressed in CHO cells at -80 mV holding voltage ... 36883854
C-X-C chemokine receptor type 3 IC50 = 56.3 nM 7.25 Antagonist activity at CXCR3 (unknown origin) in human T cells in venous blood a... 36883854
C-X-C chemokine receptor type 3 IC50 = 56.0 nM 7.25 Antagonist activity at CXCR3 in human whole blood assessed as receptor internali... 36883854
C-X-C chemokine receptor type 3 IC50 = 161.0 nM 6.79 Antagonist activity at CXCR3 in DBA/1 mouse whole blood assessed as receptor int... 36883854
C-X-C chemokine receptor type 3 IC50 = 291.0 nM 6.54 Antagonist activity at CXCR3 in Wistar rat whole blood assessed as receptor inte... 36883854

Literature References

PubMed DOI Target Context # Activities
36883854 10.1021/acs.jmedchem.3c00074 ADMET 75
36883854 10.1021/acs.jmedchem.3c00074 C-X-C chemokine receptor type 3 21
36883854 10.1021/acs.jmedchem.3c00074 No relevant target 5
36883854 10.1021/acs.jmedchem.3c00074 Voltage-gated inwardly rectifying potassium channel KCNH2 3
36883854 10.1021/acs.jmedchem.3c00074 Cytochrome P450 2D6 3
36883854 10.1021/acs.jmedchem.3c00074 Cytochrome P450 3A4 3
36883854 10.1021/acs.jmedchem.3c00074 Solute carrier organic anion transporter family member 1B3 2
36883854 10.1021/acs.jmedchem.3c00074 Solute carrier organic anion transporter family member 1B1 2
36883854 10.1021/acs.jmedchem.3c00074 ATP-dependent translocase ABCB1 2
36883854 10.1021/acs.jmedchem.3c00074 Unchecked 2
36883854 10.1021/acs.jmedchem.3c00074 Cytochrome P450 2C9 2
36883854 10.1021/acs.jmedchem.3c00074 Mus musculus 2
36883854 10.1021/acs.jmedchem.3c00074 N-formyl peptide receptor 2 1
36883854 10.1021/acs.jmedchem.3c00074 C3a anaphylatoxin chemotactic receptor 1
36883854 10.1021/acs.jmedchem.3c00074 NIH3T3 1
36883854 10.1021/acs.jmedchem.3c00074 fMet-Leu-Phe receptor 1
36883854 10.1021/acs.jmedchem.3c00074 C-X-C chemokine receptor type 6 1
36883854 10.1021/acs.jmedchem.3c00074 C-X-C chemokine receptor type 5 1
36883854 10.1021/acs.jmedchem.3c00074 C-X-C chemokine receptor type 4 1
36883854 10.1021/acs.jmedchem.3c00074 C-C chemokine receptor type 7 1

Data from ChEMBL 36 via Core Engine