REMIBRUTINIB |
REMIBRUTINIB : Covalent Inhibitor of BTK
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
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Probe Summary
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| Targets | Biochemical/Biophysical Potency | Cellular Potency |
|---|---|---|
| BTK |
|
|
Covalent Inhibitor
up to 1 uM
Selectivity
In Vitro Selectivity Assessment
Potency Assay Off-Target:
The selectivity of LOU064 was assessed in a selected panel of enzymatic kinase assays against 395 h ...
Selectivity Assessment Description:
In this screen (KINOMEscan, DiscoverX), LOU064 at a concentration of 1 μM showed full inhibition of ...
In Vitro Selectivity Assessment
Potency Assay Off-Target:
Kds were assessed in a competition binding assay for a set of Cys-containing kinases.
Selectivity Assessment Description:
LOU064 showed very potent affinity to BTK with a subnanomolar Kd of 0.63 nM and with a selectivity o ...
In Cell Selectivity Assessment
Potency Assay Off-Target:
The cellular selectivity of LOU064 was assessed in a panel of culture systems with primary human cel ...
Selectivity Assessment Description:
The main activity detected was in the BT panel and represents the intended inhibition of cellular BT ...
In Vitro Selectivity Assessment
Potency Assay Off-Target:
LOU064 was tested against a broad panel of in vitro assays (in binding or in functional mode) compri ...
Selectivity Assessment Description:
LOU064 did not show binding, inhibition, or activation in any of these assays at concentrations up t ...
Potency Cellular
In Vitro
BTK
Mode of Action: Covalent Inhibitor
Structure-Activity-Relationship data available? No
DOI Reference: 10.1021/acs.jmedchem.9b01916
In Vivo Validations
Rat
Dose: 1 mg/Kg IV, 3 mg/Kg PO
Route of delivery:
Intravenous, Oral
Plasma half life:
0.5 ± 0.03 h
Systemic clearance:
44 ± 12 mL/min/Kg
Cmax:
148 ± 33 nM
Tmax:
0.3 h
Area Under the Curve::
225 ± 27 nM·h
Bioavailability:
29 ± 3%
Volume of Distribution at Steady-State:
1.4 ± 0.3 L/Kg
DOI Reference: 10.1021/acs.jmedchem.9b01916
Mouse
Dose: 1 mg/Kg IV, 3 mg/Kg PO
Route of delivery:
Intravenous, Oral
Plasma half life:
1.0 ± 0.1 h
Systemic clearance:
97 ± 11 mL/min/Kg
Cmax:
53 ± 14 nM
Tmax:
0.3 ± 0.1 h
Area Under the Curve::
54 ± 15 nM·h
Bioavailability:
16 ± 4%
Volume of Distribution at Steady-State:
1.0 ± 0.1 L/Kg
DOI Reference: 10.1021/acs.jmedchem.9b01916
Dog
Dose: 1 mg/Kg, 3 mg/Kg
Route of delivery:
Intravenous, Oral
Plasma half life:
0.9 ± 0.1 h
Systemic clearance:
29 ± 4 mL/min/Kg
Cmax:
19 nM
Tmax:
0.8 h
Area Under the Curve::
55 nM·h
Bioavailability:
5%
Volume of Distribution at Steady-State:
1.0 ± 0.1 L/Kg
DOI Reference: 10.1021/acs.jmedchem.9b01916
Chemical Information
| Molecular Formula | C27H27F2N5O3 |
| SMILEs | C=CC(=O)N(C)CCOc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C |
| InChI | InChI=1S/C27H27F2N5O3/c1-4-23(35)34(3)9-10-37-25-24(31-14-32-26(25)30)20-12-18(28)13-22(15(20)2)33-27(36)19-8-7-17(11-21(19)29)16-5-6-16/h4,7-8,11-14,16H,1,5-6,9-10H2,2-3H3,(H,33,36)(H2,30,31,32) |
| Molecular weight | 507.21 Da |
| AlogP | 4.465320000000002 |
| HBond acceptors | 8 |
| HBond donors | 3 |
| Atoms | 64 |