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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
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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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
InChI Key XSOATTNBVDAEAR-QGHWPEOCSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Classification Click here for help
Compound class Synthetic organic
Ligand families/groups PROTACs, molecular glues and other degraders
Database Links Click here for help
GtoPdb PubChem SID 464244150
PubChem CID 163358787
Search Google for chemical match using the InChIKey XSOATTNBVDAEAR-QGHWPEOCSA-N
Search Google for chemicals with the same backbone XSOATTNBVDAEAR
UniChem Compound Search for chemical match using the InChIKey XSOATTNBVDAEAR-QGHWPEOCSA-N
UniChem Connectivity Search for chemical match using the InChIKey XSOATTNBVDAEAR-QGHWPEOCSA-N