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Borussertib | Borussertib : Covalent-allosteric inhibitor of AKT2, AKT1
RATINGS:
Cellular Use: (1 reviews)

In Model Organisms: (1 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
AKT2
  • IC50:59 nM
  • IC50:68 nM
AKT1
  • IC50:0.8 nM
  • IC50:21 nM
  • EC50:5 nM
  • EC50:50 nM
  • EC50:190 nM
Covalent Inhibitor
up to 1 uM

Selectivity

In Vitro Selectivity Assessment
Selectivity Assessment Description:
Selectivity within target family- AKT3: IC50 = 650 ± 170 nM (HTFR); IC50 = 4.3 µM (NanoBRET). Select ...

Potency
Cellular
In Vitro

AKT2

Mode of Action: Covalent Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1158/0008-5472.CAN-18-2861

AKT1

Mode of Action: Covalent Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1158/0008-5472.CAN-18-2861

In Vivo Validations

Mouse
Dose: 2 mg/Kg
Route of delivery: Intravenous
Plasma half life: 0.85 h
Systemic clearance: 5.77 L/h/Kg
Cmax: 623.37 ng/mL
Tmax: 0.08 h
Area Under the Curve:: 303.7 h*ng/mL
Volume of Distribution at Steady-State: 4.94 L/Kg

DOI Reference: 10.1158/0008-5472.CAN-18-2861

Dose: 20 mg/Kg
Route of delivery: Intraperitoneal
Cmax: 683.53 ng/mL
Tmax: 0.75 h
Area Under the Curve:: 1201.3 h*ng/mL
Bioavailability: 40%

DOI Reference: 10.1158/0008-5472.CAN-18-2861

Dose: 20 mg/Kg
Route of delivery: Oral
Cmax: 77.92 ng/mL
Tmax: 2.25 h
Area Under the Curve:: 84.6 h*ng/mL
Bioavailability: 3%

DOI Reference: 10.1158/0008-5472.CAN-18-2861

Negative Control Compounds

RL2578
Notes: RL2578: IC50 = 9.2 µM (HTRF), >1000-fold less potent in vitro compared to Borussertib CTG assay: EC50 = 4.2 µM (ZR-75-1), 18 µM (AN3-CA); NanoBRET: IC50 = 1.9 µM (AKT1), 8.3 µM (AKT2), 12 µM (AKT3)
InChI: InChI=1S/C30H29N5O4/c1-2-28(36)31-22-8-9-24-26(16-22)35(30(38)33-24)23-11-13-34(14-12-23)17-19-3-5-20(6-4-19)21-7-10-27-25(15-21)32-29(37)18-39-27/h2-10,15-16,23H,1,11-14,17-18H2,(H,31,36)(H,32,37)(H,33,38)

Orthogonal Probes def

TRAMETINIB
BAY1125976

Chemical Information

Molecular Formula C36H32N6O3
SMILEs C=C/C(O)=N/c1ccc2nc(O)n(C3CCN(Cc4ccc(-c5nc6ccnc(O)c6cc5-c5ccccc5)cc4)CC3)c2c1
InChI InChI=1S/C36H32N6O3/c1-2-33(43)38-26-12-13-31-32(20-26)42(36(45)40-31)27-15-18-41(19-16-27)22-23-8-10-25(11-9-23)34-28(24-6-4-3-5-7-24)21-29-30(39-34)14-17-37-35(29)44/h2-14,17,20-21,27H,1,15-16,18-19,22H2,(H,37,44)(H,38,43)(H,40,45)
Molecular weight 596.25 Da
AlogP 0.0
HBond acceptors 9
HBond donors 3
Atoms 77

Vendors

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Expert Reviews

by SERP
(on 1 Mar 2022 )
Cellular Use Rating
In Model Organisms
I would not recommend dosing with this compound orally.

Portal Comments

In a 2023 study, Hu et al. evaluated Borussertib in live-cell assays for Phospholipidosis induction, cautioning about adverse effects at concentrations near 1 uM. (DOI:10.1016/j.chembiol.2023.09.003)

(last updated: 7 Nov 2023)

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