SIAIS178   Click here for help

GtoPdb Ligand ID: 10526

Synonyms: compound 19 [PMID: 31539241] | SIAIS-178
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: 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.
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2D Structure
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Physico-chemical Properties
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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
SMILES / InChI / InChIKey
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Canonical SMILES OC1CC(N(C1)C(=O)C(C(C)(C)C)NC(=O)CCCCCCC(=O)N1CCN(CC1)c1nc(C)nc(c1)Nc1ncc(s1)C(=O)Nc1c(C)cccc1Cl)C(=O)NCc1ccc(cc1)c1scnc1C
Isomeric SMILES O[C@@H]1C[C@H](N(C1)C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCC(=O)N1CCN(CC1)c1nc(C)nc(c1)Nc1ncc(s1)C(=O)Nc1c(C)cccc1Cl)C(=O)NCc1ccc(cc1)c1scnc1C
InChI InChI=1S/C50H62ClN11O6S2/c1-30-12-11-13-36(51)43(30)59-47(67)38-27-53-49(70-38)57-39-25-40(56-32(3)55-39)60-20-22-61(23-21-60)42(65)15-10-8-7-9-14-41(64)58-45(50(4,5)6)48(68)62-28-35(63)24-37(62)46(66)52-26-33-16-18-34(19-17-33)44-31(2)54-29-69-44/h11-13,16-19,25,27,29,35,37,45,63H,7-10,14-15,20-24,26,28H2,1-6H3,(H,52,66)(H,58,64)(H,59,67)(H,53,55,56,57)/t35-,37+,45-/m1/s1
InChI Key YGQREOJIRFCRKQ-ZIBKGDFVSA-N
Classification Click here for help
Compound class Synthetic organic
Ligand families/groups PROTACs, molecular glues and other degraders
IUPAC Name Click here for help
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 Click here for help
compound 19 [PMID: 31539241] | SIAIS-178
Database Links Click here for help
GtoPdb PubChem SID 387065608
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