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TNO155 | TNO155 : Allosteric of PTPN11
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
PTPN11
  • IC50:11 nM
  • IC50:11 nM
  • IC50:100 nM
Allosteric
up to 1 uM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
Completely selective over panels of phosphatases and kinases based on screening in commercial panels ...

Potency
Cellular
In Vitro

PTPN11

Mode of Action: Allosteric

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.0c01170

In Vivo Validations

Mouse
Dose: 1 mg/Kg
Route of delivery: Intravenous
Plasma half life: 2 h
Systemic clearance: 24 mL/min/kg
Area Under the Curve:: 1530 nM*h
Fb : 76%
Volume of Distribution at Steady-State: 3 L/Kg

DOI Reference: 10.1021/acs.jmedchem.0c01170

Dose: 5 mg/Kg
Route of delivery: Oral
Cmax: 357 nM
Tmax: 0.8 h
Area Under the Curve:: 1190 nM*h
Bioavailability: 78%

DOI Reference: 10.1021/acs.jmedchem.0c01170

Rat
Dose: 1 mg/Kg
Route of delivery: Intravenous
Plasma half life: 8 h
Systemic clearance: 15 mL/min/Kg
Area Under the Curve:: 2407 nM*h
Fb : 81%
Volume of Distribution at Steady-State: 7 L/Kg

DOI Reference: 10.1021/acs.jmedchem.0c01170

Dose: 5 mg/Kg
Route of delivery: Oral
Cmax: 657 nM
Tmax: 1 h
Area Under the Curve:: 2483 nM*h
Bioavailability: 100%

DOI Reference: 10.1021/acs.jmedchem.0c01170

Dog
Dose: 0.2 mg/Kg
Route of delivery: Intravenous
Plasma half life: 9 h
Systemic clearance: 4 mL/min/Kg
Area Under the Curve:: 10690 nM*h
Fb : 64%
Volume of Distribution at Steady-State: 3 L/Kg

DOI Reference: 10.1021/acs.jmedchem.0c01170

Dose: 1 mg/Kg
Route of delivery: Oral
Cmax: 1207 nM
Tmax: 2 h
Area Under the Curve:: 15854 nM*h
Bioavailability: >100%

DOI Reference: 10.1021/acs.jmedchem.0c01170

Monkey (Cynomolgus)
Dose: 0.3 mg/Kg
Route of delivery: Intravenous
Plasma half life: 9 h
Systemic clearance: 6 mL/min/Kg
Area Under the Curve:: 6438 nM*h
Fb : 61%
Volume of Distribution at Steady-State: 4 L/Kg

DOI Reference: 10.1021/acs.jmedchem.0c01170

Dose: 1 mg/Kg
Route of delivery: Oral
Cmax: 286 nM
Tmax: 2 h
Area Under the Curve:: 3848 nM*h
Bioavailability: 60%

DOI Reference: 10.1021/acs.jmedchem.0c01170

Negative Control Compounds

CANSAR3148275
Notes: cpd 6 SHP2 IC50 1.3 uM

Chemical Information

Molecular Formula C18H24ClN7OS
SMILEs C[C@@H]1OCC2(CCN(c3cnc(Sc4ccnc(N)c4Cl)c(N)n3)CC2)[C@@H]1N
InChI InChI=1S/C18H24ClN7OS/c1-10-14(20)18(9-27-10)3-6-26(7-4-18)12-8-24-17(16(22)25-12)28-11-2-5-23-15(21)13(11)19/h2,5,8,10,14H,3-4,6-7,9,20H2,1H3,(H2,21,23)(H2,22,25)/t10-,14+/m0/s1
Molecular weight 421.15 Da
AlogP 0.0
HBond acceptors 8
HBond donors 6
Atoms 52

References

Publications

Cross References

canSARChEMBLBindingDBPDB

Vendors

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Expert Reviews

by SERP
(on 8 Nov 2022 )
Cellular Use Rating
In Model Organisms
TNO155 has an interesting mechanism-of-action, acting at a key allosteric site to block SHP2 activity. It is recommended for use in studying this phosphatase, especially in combination with other inhibitors...
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