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
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.
Database Links
BindingDB Ligand 50388183
ChEMBL Ligand CHEMBL2057915
GtoPdb PubChem SID 315661338
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)