ARD-266   

GtoPdb Ligand ID: 10579

Synonyms: compound 11 [PMID: 31804827]
Compound class: Synthetic organic
Comment: ARD-266 is a potent proteolysis-targeting chimera (PROTAC) degrader of the androgen receptor (AR) [1]. Its design highlights that using an E3 ligase ligand with low affinity (Ki of 2-3 μM) in a PROTAC can still achieve a very potent degrading effect against the AR. Ubiquitination and proteasomal degradation is mediated by the compound's ligand that binds to the VHL constituent of the VHL/cullin2 E3 ligase complex. The AR antagonist component of ARD-266 is the same as that utilised in the previously reported AR degrader, ARD-69.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 10
Hydrogen bond donors 3
Rotatable bonds 16
Topological polar surface area 178.1
Molecular weight 914.41
XLogP 7.97
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
Canonical SMILES N#Cc1ccc(cc1Cl)OC1C(C)(C)C(C1(C)C)NC(=O)c1ccc(cc1)C#CC1CCN(CC1)C(=O)CC(c1ccccc1)NC(=O)C1CC(CN1C(=O)C(c1onc(c1)C)C(C)C)O
Isomeric SMILES N#Cc1ccc(cc1Cl)O[C@@H]1C(C)(C)[C@H](C1(C)C)NC(=O)c1ccc(cc1)C#CC1CCN(CC1)C(=O)C[C@@H](c1ccccc1)NC(=O)[C@@H]1C[C@H](CN1C(=O)[C@@H](c1onc(c1)C)C(C)C)O
InChI InChI=1S/C52H59ClN6O7/c1-31(2)45(43-25-32(3)57-66-43)48(64)59-30-38(60)26-42(59)47(63)55-41(35-11-9-8-10-12-35)28-44(61)58-23-21-34(22-24-58)14-13-33-15-17-36(18-16-33)46(62)56-49-51(4,5)50(52(49,6)7)65-39-20-19-37(29-54)40(53)27-39/h8-12,15-20,25,27,31,34,38,41-42,45,49-50,60H,21-24,26,28,30H2,1-7H3,(H,55,63)(H,56,62)/t38-,41+,42+,45-,49-,50-/m1/s1
InChI Key RTNONCBKGZNCJS-LJLQSONVSA-N
Classification
Compound class Synthetic organic
Ligand families/groups PROTACs and molecular glues
IUPAC Name
(2S,4R)-N-((S)-3-(3-(4-((4-(((1r,3r)-3-(3-Chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)carbamoyl)phenyl)ethynyl)piperidin-1-yl)azetidin-1-yl)-3-oxo-1-phenylpropyl)-4-hydroxy-1-((R)-3-methyl-2-(3-methylisoxazol-5-yl)butanoyl)pyrrolidine-2-carboxamide
Synonyms
compound 11 [PMID: 31804827]
Database Links
GtoPdb PubChem SID 404859026
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