TYRA-300 | TYRA-300 : Inhibitor of FGFR3
RATINGS:
Cellular Use: (0 reviews)

In Model Organisms: (0 reviews)
Control Compounds

Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
FGFR3 (Mutant:WT, G380R, N540K)
  • IC50:1.6 nM
  • IC50:21 nM
  • IC50:9 - 21 nM
  • IC50:11 nM
Inhibitor
up to 100 nM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
Selectivity of TYRA-300 for the human kinome was assessed with a KINOMEscan (Eurofins, San Diego, CA ...
In Cell Selectivity Assessment
Potency Assay Off-Target:
In BaF3 cellular assay TYRA-300 showed to be selective for FGFR3 against FGFR1, 2, and 4.

Potency
Cellular
In Vitro

FGFR3 (Mutant:WT, G380R, N540K)

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.4c01531

In Vivo Validations

Rat
Dose: 2 mg/Kg
Route of delivery: Intravenous
Plasma half life: 1.93 h
Systemic clearance: 17.5 mL/min/Kg
Area Under the Curve:: 1734 h·ng/mL
Volume of Distribution at Steady-State: 2.5 L/Kg

DOI Reference: 10.1021/acs.jmedchem.4c01531

Dose: 10 mg/Kg
Route of delivery: Oral
Cmax: 802 ± 198 ng/mL
Tmax: 4 h
Area Under the Curve:: 3355 ±892h·ng/mL
Bioavailability: 39 ± 10%

DOI Reference: 10.1021/acs.jmedchem.4c01531

Dog
Dose: 1 mg/Kg
Route of delivery: Intravenous
Plasma half life: 5.52 ± 0.34 h
Systemic clearance: 2.68 ± 0.15 mL/min/kg
Area Under the Curve:: 5930 ± 298 h·ng/mL
Volume of Distribution at Steady-State: 1.12 ± 0.05 L/Kg

DOI Reference: 10.1021/acs.jmedchem.4c01531

Dose: 10 mg/Kg
Route of delivery: Oral
Plasma half life: 24.8 h
Cmax: ng/mL
Tmax: 6.0 ± 1.6 h
Area Under the Curve:: 58300 ± 1810 h·ng/mL
Bioavailability: 98 ± 3%

DOI Reference: 10.1021/acs.jmedchem.4c01531

Monkey (Cynomolgus)
Dose: 1 mg/Kg
Route of delivery: Intravenous
Plasma half life: 1.17 ± 0.15 h
Systemic clearance: 11.07 ± 0.66 mL/min/kg
Area Under the Curve:: 1500 ± 86 h·ng/mL
Volume of Distribution at Steady-State: 0.94 ± 0.12 L/Kg

DOI Reference: 10.1021/acs.jmedchem.4c01531

Dose: 10 mg/Kg
Route of delivery: Oral
Cmax: 1210 ± 742 ng/mL
Tmax: 6.0 h
Area Under the Curve:: 15900 ± 8080 h·ng/mL
Bioavailability: 106 ± 54 %

DOI Reference: 10.1021/acs.jmedchem.4c01531

Chemical Information

Molecular Formula C25H24Cl2N6O3S
SMILEs C[C@@H](Oc1ccc2[nH]nc(-c3ccc(N4CC5(C4)CN(S(C)(=O)=O)C5)nc3)c2c1)c1c(Cl)cncc1Cl
InChI InChI=1S/C25H24Cl2N6O3S/c1-15(23-19(26)9-28-10-20(23)27)36-17-4-5-21-18(7-17)24(31-30-21)16-3-6-22(29-8-16)32-11-25(12-32)13-33(14-25)37(2,34)35/h3-10,15H,11-14H2,1-2H3,(H,30,31)/t15-/m1/s1
Molecular weight 558.10 Da
AlogP 4.548300000000004
HBond acceptors 9
HBond donors 1
Atoms 61

References

Cross References

Vendors

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Expert Reviews


No SERP comments found for TYRA-300

Probe TYRA-300 is in the process of SERP review.

Please continue to check back for new reviews and commentary.