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AG-270 | AG-270 : Allosteric Inhibitor of MAT2A
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (3 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
MAT2A
  • IC50:14 nM
  • % in:91 %
  • IC50:20 nM
  • IC50:257 nM
Allosteric
up to 1 uM

Selectivity

In Vitro Selectivity Assessment
Selectivity Assessment Description:
<strong>Outside target family:</strong> assessment of AG-270 specificity in in vitro binding assa ...

Potency
Cellular
In Vitro

MAT2A

Mode of Action: Allosteric

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.0c01895

In Vivo Validations

Mouse, Rat, Dog, Cyno
Dose: 10-200 mg/Kg
Route of delivery: Oral
Plasma half life: 5.9 (M), 4.2 (R), 4.8 (C) 21.3 (D)
Systemic clearance: 0.0804 (M), 0.47 (R), 0.06 (C), 0.04 (D) L/h/Kg
Organ of interest (O): Xenograft
Target engagement assay: Led to dose-dependent reductions in tumor SAM levels and tumor growth of KP4 MTAP-null xenografts (TGI = 36% (10 mg/kg), 48% (30 mg/kg), 66% (100 mg/kg), 67% (200 mg/kg).

DOI Reference: 10.1021/acs.jmedchem.0c01895

Negative Control Compounds

AGI-38053

Orthogonal Probes def

8AJ

Chemical Information

Molecular Formula C30H27N5O2
SMILEs COc1ccc(-c2c(Nc3ccccn3)[nH]c3c(C4=CCCCC4)c(-c4ccccc4)nn3c2=O)cc1
InChI InChI=1S/C30H27N5O2/c1-37-23-17-15-21(16-18-23)26-28(32-24-14-8-9-19-31-24)33-29-25(20-10-4-2-5-11-20)27(34-35(29)30(26)36)22-12-6-3-7-13-22/h3,6-10,12-19,33H,2,4-5,11H2,1H3,(H,31,32)
Molecular weight 489.22 Da
AlogP 6.461200000000005
HBond acceptors 7
HBond donors 2
Atoms 64

References

Publications

Cross References

canSARChEMBLBindingDBPDB

Vendors

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Expert Reviews

by SERP
(on 18 Jun 2021 )
Cellular Use Rating
In Model Organisms
AG-270 is a well-characterised tool compound for the study of allosteric MAT2A inhibition both in cells and in vivo mouse models at the recommended concentration and dose ranges. However, AG-270 has...
by SERP
(on 22 Jun 2021 )
Cellular Use Rating
In Model Organisms
The compound is poorly soluble thus special care must be taken when preparing formulations for in vivo work. Specifically, the compound must be prepared as a spray-dried dispersion.
by SERP
(on 30 Jun 2021 )
Cellular Use Rating
In Model Organisms
AG-270 was developed from a relatively weak binder and abundant SAR data and co-crystal structures with its intended target MAT2A, demonstrate the inhibition mechanism. Cellular and in vivo effects...
Note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars. Read more about our evaluation criteria