XL01126   Click here for help

GtoPdb Ligand ID: 12009

Compound class: Synthetic organic
Comment: XL01126 is a VHL-based PROTAC degrader targeting leucine rich repeat kinase 2 (LRRK2). The LRRK2 binding moeity of the compound is the brain-penetrant kinase inhibitor HG-10-102-01. XL01126 is orally bioavailable and retains the ability of the parent kinase inhibitor to cross the blood-brain barrier. LRRK2 is an active therapeutic target for Parkinson's disease, since activating coding mutations in LRRK2 are associated with dominantly inherited Parkinson's disease [1-2,5]. XL01126's development was led by Dundee University's Centre for Targeted Protein Degradation and the Research Institute for Medicines at the University of Lisbon. Initially disclosed in a ChemRxiv preprint [4].

Cereblon-targeting LRRK2 PROTACs have been disclosed previously, but these were found to be inefficient target degraders [3].
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 15
Hydrogen bond donors 5
Rotatable bonds 22
Topological polar surface area 247.79
Molecular weight 998.47
XLogP 5.05
No. Lipinski's rules broken 3
Click here for help
Canonical SMILES COc1cc(ccc1Nc1ncc(c(n1)NC)C)C(=O)N1CCN(CC1)C[C@@H]1CC[C@H](CC1)CSC([C@@H](C(=O)N1C[C@@H](C[C@H]1C(=O)NCc1ccc(cc1)c1scnc1C)O)NC(=O)C1(F)CC1)(C)C
Isomeric SMILES CNc1nc(Nc2ccc(cc2OC)C(=O)N2CCN(C[C@H]3CC[C@H](CSC(C)(C)[C@H](NC(=O)C4(F)CC4)C(=O)N4C[C@H](O)C[C@H]4C(=O)NCc4ccc(cc4)c4scnc4C)CC3)CC2)ncc1C
InChI InChI=1S/C51H67FN10O6S2/c1-31-25-55-49(59-44(31)53-5)57-39-16-15-37(23-41(39)68-6)46(65)61-21-19-60(20-22-61)27-34-7-9-35(10-8-34)29-70-50(3,4)43(58-48(67)51(52)17-18-51)47(66)62-28-38(63)24-40(62)45(64)54-26-33-11-13-36(14-12-33)42-32(2)56-30-69-42/h11-16,23,25,30,34-35,38,40,43,63H,7-10,17-22,24,26-29H2,1-6H3,(H,54,64)(H,58,67)(H2,53,55,57,59)/t34-,35-,38-,40+,43-/m1/s1
Download 2D Structure Click here for help
Canonical SMILES Download
Isomeric SMILES Download
InChI standard identifier Download
InChI standard key Download

Molecular structure representations generated using Open Babel