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AS-99 | AS-99 : SET non-competitive inhibitor of ASH1L
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
ASH1L
  • IC50, KD:790 nM; 890 nM
  • GI50:1800 - 3600 nM
Inhibitor
up to 6 uM

Selectivity

In Vitro Selectivity Assessment
Selectivity Assessment Description:
 >100-fold selectivity of AS-99 to ASH1L over other HMTs @ 50 uM>100-fold se ...

Potency
Cellular
In Vitro

ASH1L

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1038/s41467-021-23152-6

In Vivo Validations

Mouse
Dose: 15 mg/Kg IV, 30 mg/Kg IP
Route of delivery: Intraperitoneal, Intravenous
Plasma half life: 5.19 (IV), 6.79 (IP) h
Systemic clearance: 1546.5 (IV), 2803.9 (IP) mL/h/Kg

DOI Reference: 10.1038/s41467-021-23152-6

Negative Control Compounds

canSAR4558227
Notes: ~100-fold reduced inhibitory activity, IC50 of 72 µM for AS-nc

Chemical Information

Molecular Formula C27H30F3N5O3S2
SMILEs CN1CC(C(=O)NCc2ccc3c(-c4cccc(C(N)=S)c4)cn(C4CCN(S(=O)(=O)C(F)(F)F)CC4)c3c2)C1
InChI InChI=1S/C27H30F3N5O3S2/c1-33-14-20(15-33)26(36)32-13-17-5-6-22-23(18-3-2-4-19(12-18)25(31)39)16-35(24(22)11-17)21-7-9-34(10-8-21)40(37,38)27(28,29)30/h2-6,11-12,16,20-21H,7-10,13-15H2,1H3,(H2,31,39)(H,32,36)
Molecular weight 593.17 Da
AlogP 0.0
HBond acceptors 8
HBond donors 3
Atoms 70

References

Publications

Cross References

canSARChEMBL

Vendors

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Expert Reviews

by SERP
(on 29 Jun 2021 )
Cellular Use Rating
In Model Organisms
AS-99 is the first selective ASH1L inhibitor and an excellent chemical probe.
by SERP
(on 5 Jul 2021 )
Cellular Use Rating
In Model Organisms
The active compound is a thioamide, metabolic to inactive amide may apply dependent on animal model but good PK was shown in this study.
by SERP
(on 6 Jul 2021 )
Cellular Use Rating
In Model Organisms
ASH1 is an important epigenetic target. Before this report, there is no high-quality ASH1 inhibitor. AS-99 is the first small-molecular inhibitor of ASH1 with a decent IC50 and promising cellular activity....
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