BMS-986449 |
BMS-986449 : CELMoD Dual Degrader of IKZF2, IKZF4
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary
| Targets | Biochemical/Biophysical Potency | Cellular Potency |
|---|---|---|
| IKZF2 |
|
|
| IKZF4 |
|
up to 100 nM
Selectivity
In Cell Selectivity Assessment
Potency Assay Off-Target:
Global proteomics study of Jurkat cells treated with titrated concentrations of BMS-986449 enabled a ...
Selectivity Assessment Description:
BMS-986449 is highly selective across the proteome, including against other known neosubstrates of C ...
In Cell Selectivity Assessment
Potency Assay Off-Target:
Seletivity within target family: BMS-986449 was selective against IKZF1, IKZF3, and GSPT1 in Cellula ...
Potency Cellular
In Vitro
IKZF2
Mode of Action: CELMoD Degrader
Structure-Activity-Relationship data available? Yes
DOI Reference: 10.1021/acs.jmedchem.6c01271
IKZF4
Mode of Action: CELMoD Degrader
Structure-Activity-Relationship data available? Yes
DOI Reference: 10.1021/acs.jmedchem.6c01271
In Vivo Validations
Mouse
Dose: 1 mg/Kg IV, 2 mg/Kg PO
Route of delivery:
Intravenous, Oral
Plasma half life:
4.0 h
Systemic clearance:
16 mL/min/Kg
Cmax:
0.7 ug/mL
Tmax:
0.5 h
Area Under the Curve::
1.1 IV, 1.3 PO μg h/mL
Bioavailability:
57%
Volume of Distribution at Steady-State:
1.3 L/Kg
DOI Reference: 10.1021/acs.jmedchem.6c01271
Rat
Dose: 1 mg/Kg IV, 5 mg/Kg PO
Route of delivery:
Intravenous, Oral
Plasma half life:
4.6 h
Systemic clearance:
16 mL/min/Kg
Cmax:
2.5 ug/mL
Tmax:
0.5 h
Area Under the Curve::
1.2 IV, 4.6 PO ug h/mL
Bioavailability:
87%
Volume of Distribution at Steady-State:
1.2 L/Kg
DOI Reference: 10.1021/acs.jmedchem.6c01271
Dog
Dose: 0.5 mg/Kg IV and PO
Route of delivery:
Intravenous, Oral
Plasma half life:
12.4 h
Systemic clearance:
9.5 mL/min/Kg
Cmax:
0.3 ug/mL
Tmax:
0.8h
Area Under the Curve::
0.9 ug h/mL IV and PO
Bioavailability:
86%
Volume of Distribution at Steady-State:
2.5 L/Kg
DOI Reference: 10.1021/acs.jmedchem.6c01271
Monkey (Cynomolgus)
Dose: 0.3 mg/Kg IV and PO
Route of delivery:
Intravenous, Oral
Plasma half life:
15.9 h
Systemic clearance:
4.0 mL/min/Kg
Cmax:
0.1 ug/mL
Tmax:
2 h
Area Under the Curve::
1.3 IV, 0.9 PO ug h/mL
Bioavailability:
77%
Volume of Distribution at Steady-State:
3.4 L/Kg
DOI Reference: 10.1021/acs.jmedchem.6c01271
Chemical Information
| Molecular Formula | C21H21FN4O3 |
| SMILEs | Cc1cc(-c2ccc3c(c2F)[C@@H](C)N([C@H]2CCC(=O)NC2=O)C3=O)nc(N)c1C |
| InChI | InChI=1S/C21H21FN4O3/c1-9-8-14(24-19(23)10(9)2)12-4-5-13-17(18(12)22)11(3)26(21(13)29)15-6-7-16(27)25-20(15)28/h4-5,8,11,15H,6-7H2,1-3H3,(H2,23,24)(H,25,27,28)/t11-,15+/m1/s1 |
| Molecular weight | 396.16 Da |
| AlogP | 2.40874 |
| HBond acceptors | 7 |
| HBond donors | 3 |
| Atoms | 50 |