GtoPdb Ligand ID: 9653

Compound class: Synthetic organic
Comment: GSK866 is a prototype of a class of compounds called selective glucocorticoid receptor agonists (SEGRAs). SEGRAs exert their pharmacological effect by activation of only the transrepression pathway, which is in contrast to traditional glucocorticosteroids which activate both the transactivation and transrepression pathways. Development of SEGRAs is aiming to improve the risk-benefit profile associated with use of traditional glucocorticosteroids drugs. See also our entry for mapracorat, a SEGRA that advanced to clinical trial. GSK866 is example 1 in [1], which is shown bound to the glucocortocoid receptor in the X-ray structure 3E7C. A series of novel covalently binding SEGRAs based on the structure of GSK866 is reported in [2]. Note that there is some ambiguity in the literature and online chemistry resources as to the precise stereochemistry of this ligand. We show the S isomer as specificed by the SMILES string supplied in the PDB entry.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 7
Hydrogen bond donors 3
Rotatable bonds 11
Topological polar surface area 112.96
Molecular weight 561.1
XLogP 5.52
No. Lipinski's rules broken 1
Canonical SMILES CCN(C(=O)c1c(Cl)cccc1Cl)CC(C(F)(F)F)(CNC(=O)c1cnn(c1N)c1ccc(cc1)F)O
Isomeric SMILES CCN(C(=O)c1c(Cl)cccc1Cl)C[C@](C(F)(F)F)(CNC(=O)c1cnn(c1N)c1ccc(cc1)F)O
InChI InChI=1S/C23H21Cl2F4N5O3/c1-2-33(21(36)18-16(24)4-3-5-17(18)25)12-22(37,23(27,28)29)11-31-20(35)15-10-32-34(19(15)30)14-8-6-13(26)7-9-14/h3-10,37H,2,11-12,30H2,1H3,(H,31,35)/t22-/m0/s1
Compound class Synthetic organic
Database Links
GtoPdb PubChem SID 340590283
PubChem CID 25058139
RCSB PDB Ligand 866
Search Google for chemical match using the InChIKey LKQMULLPLYLIGW-QFIPXVFZSA-N
Search Google for chemicals with the same backbone LKQMULLPLYLIGW
Search UniChem for chemical match using the InChIKey LKQMULLPLYLIGW-QFIPXVFZSA-N
Search UniChem for chemicals with the same backbone LKQMULLPLYLIGW
SynPHARM 84539 (in complex with Glucocorticoid receptor)