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LLY-283 | LLY-283 : a SAM competitive inhibitor of PRMT5
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
PRMT5
  • IC50:22 ± 3 nM
  • Kd:6 ± 2 nM
  • IC50:25 ± 1 nM
  • EC50:37 ± 3 nM
  • IC50:46 ± 5 nM
SAM Noncompetitive
up to 1 uM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
Selectivity of compounds LLY-283 and LLY-284 at 1 and 10 μM (as indicated on the plot) were assessed ...

Potency
Cellular
In Vitro

PRMT5

Mode of Action: SAM Noncompetitive

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acsmedchemlett.8b00014

In Vivo Validations

Mouse
Dose: 10 mg/Kg
Route of delivery: Oral
Plasma half life: 3.41 h
Systemic clearance: 12.6 mL/min/Kg
Cmax: 3646 ng/mL
Area Under the Curve:: 7943 ng*h/mL
Fb : 99.46%
Bioavailability: 50%
Volume of Distribution at Steady-State: 1819 mL/Kg

DOI Reference: 10.1021/acsmedchemlett.8b00014

Negative Control Compounds

CANSAR1684258
Notes: LLY-284 5′-stereoisomer, compound 2, was almost 50-fold less active (IC50 of 1074 ± 53 nM)

Orthogonal Probes def

EPZ015666
GSK591
DS-437

Chemical Information

Molecular Formula C17H18N4O4
SMILEs Nc1ncnc2c1ccn2[C@@H]1O[C@H]([C@H](O)c2ccccc2)[C@@H](O)[C@H]1O
InChI InChI=1S/C17H18N4O4/c18-15-10-6-7-21(16(10)20-8-19-15)17-13(24)12(23)14(25-17)11(22)9-4-2-1-3-5-9/h1-8,11-14,17,22-24H,(H2,18,19,20)/t11-,12+,13-,14-,17-/m1/s1
Molecular weight 342.13 Da
AlogP 0.3663000000000001
HBond acceptors 8
HBond donors 5
Atoms 43

References

Publications

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Vendors

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Expert Reviews

by SERP
(on 13 Jan 2023 )
Cellular Use Rating
In Model Organisms
LLY-283 is an excellent probe, for in vitro, in cell, and in vivo studies. It is brain-penetrant and significantly prolongs the survival of mice with orthotopic patient-derived xenografts. It has been...

Portal Comments

LLY-283 has originally been suggested to be a non-competitive inhibitor or PRMT5, but a subsequent publication showed a competitive binding mode

(last updated: 16 Jan 2023)

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