SIAIS178

Ligand id: 10526

Name: SIAIS178

Structure and Physico-chemical Properties

2D Structure
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Calculated Physico-chemical Properties
Hydrogen bond acceptors 17
Hydrogen bond donors 5
Rotatable bonds 24
Topological polar surface area 271.46
Molecular weight 1011.4
XLogP 5.55
No. Lipinski's rules broken 3

Molecular properties generated using the CDK

Classification
Compound class Synthetic organic
Ligand families/groups PROTACs and molecular glues
IUPAC Name
N-(2-Chloro-6-methylphenyl)-2-((6-(4-(8-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methyl-thiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-8-oxooctanoyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide
Synonyms
compound 19 [PMID: 31539241] | SIAIS-178
Comments
SIAIS178 is a novel proteolysis-targeting chimeric (PROTAC) degrader [1]. It is a hybrid molecule that connects the BCR-ABL kinase inhibitor dasatinib to a ligand for Von Hippel-Lindau (VHL) E3 ubiquitin ligase via an optimised linker. SIAIS178 targets BCR-ABL protein for VHL-mediated degradation. The hybrid molecule exhibits an improved kinase selectivity profile compared to dasatinib (in a KINOME Scan evaluation). An epimer of SIAIS178 with a reversed (S) configuration at the proline 4-position of the VHL ligand does not bind to the VHL ligase and is inactive with respect to BCR-ABL degradation.
Database Links
GtoPdb PubChem SID 387065608
Search Google for chemical match using the InChIKey YGQREOJIRFCRKQ-ZIBKGDFVSA-N
Search Google for chemicals with the same backbone YGQREOJIRFCRKQ
Search UniChem for chemical match using the InChIKey YGQREOJIRFCRKQ-ZIBKGDFVSA-N
Search UniChem for chemicals with the same backbone YGQREOJIRFCRKQ