GDC-0834

Ligand id: 9263

Name: GDC-0834

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 9
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 113.23
Molecular weight 596.26
XLogP 4.62
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

Classification
Compound class Synthetic organic
IUPAC Name
N-[3-[6-[4-[(2R)-1,4-dimethyl-3-oxopiperazin-2-yl]anilino]-4-methyl-5-oxopyrazin-2-yl]-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide
Synonyms
GDC 0834
Database Links
BindingDB Ligand 50388183
ChEMBL Ligand CHEMBL2057915
PubChem CID 25234918
RCSB PDB Ligand 2VL
Search Google for chemical match using the InChIKey CDOOFZZILLRUQH-GDLZYMKVSA-N
Search Google for chemicals with the same backbone CDOOFZZILLRUQH
Search UniChem for chemical match using the InChIKey CDOOFZZILLRUQH-GDLZYMKVSA-N
Search UniChem for chemicals with the same backbone CDOOFZZILLRUQH
SynPHARM 83743 (in complex with Bruton tyrosine kinase)
Comments
GDC-0834 was identified as a clinical candidate antiinflammatory Bruton's tyrosine kinase (BTK) inhibitor, through SAR guided improvements to the pharmacokinetic (PK) properties of the potent and selective BTK inhibitor CGI1746 [4]. GDC-0834 retains CGI1746's selectivity but exhibits significantly improved PK in preclinical animal models [1]. Studies suggest the involvement of aldehyde oxidase (AO) in the rapid amide hydrolysis of GDC-0834 to an inactive metabolite [3], which severly impacted on its ability to sustain beneficial clinical effects. Significant species difference in AO-induced inactivation of GDC-0834 are reported and explain why this was not picked up during preclinical studies [2]. Clinical development was terminated, with the manufacturer using insight gained to inform their search for improved inhibitors.