compound 16 [PMID: 38526960]   Click here for help

GtoPdb Ligand ID: 13292

Compound class: Synthetic organic
Comment: Compound 16 is a sulphide prodrug of the sesquiterpene lactone Micheliolide (MCL; which exhibits anti-inflammatory effects [2-3]). It was designed to improve the safety profile (lower blood-brain barrier permeability) compared to the previously explored MCL prodrug ACT001, specifically to support investigation as an anti-fungal agent [1]. Like ACT001, 16 inhibits PD-L1 expression in neutrophils, via a STAT3-dependent mechanism.
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 6
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 101.58
Molecular weight 475.38
XLogP 2.25
No. Lipinski's rules broken 0

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 C[C@]1(CC[C@@]23[C@@]1([H])[C@@H]4[C@@H](CC[C@]2(C)O3)[C@H](CS(=O)(=O)C5=C(C=CC=C5Cl)Cl)C(=O)O4)O
Isomeric SMILES O=C1O[C@@H]2[C@]3([H])[C@]4(CC[C@@]3(C)O)[C@](O4)(C)CC[C@H]2[C@@H]1CS(=O)(C5=C(Cl)C=CC=C5Cl)=O
InChI InChI=1S/C21H24Cl2O6S/c1-19(25)8-9-21-17(19)15-11(6-7-20(21,2)29-21)12(18(24)28-15)10-30(26,27)16-13(22)4-3-5-14(16)23/h3-5,11-12,15,17,25H,6-10H2,1-2H3/t11-,12-,15-,17-,19+,20-,21+/m0/s1
InChI Key UZKFXCLLQZGSMT-ZTNHXCFJSA-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/)
References
1. Lu X, Wang R, Yu Y, Wei J, Xu Y, Zhou L, Mao F, Li J, Li X, Jia X. (2024)
Drug Repurposing of ACT001 to Discover Novel Promising Sulfide Prodrugs with Improved Safety and Potent Activity for Neutrophil-Mediated Antifungal Immunotherapy.
J Med Chem, 67 (7): 5783-5799. [PMID:38526960]
2. Qin X, Jiang X, Jiang X, Wang Y, Miao Z, He W, Yang G, Lv Z, Yu Y, Zheng Y. (2016)
Micheliolide inhibits LPS-induced inflammatory response and protects mice from LPS challenge.
Sci Rep, 6: 23240. [PMID:26984741]
3. Viennois E, Xiao B, Ayyadurai S, Wang L, Wang PG, Zhang Q, Chen Y, Merlin D. (2014)
Micheliolide, a new sesquiterpene lactone that inhibits intestinal inflammation and colitis-associated cancer.
Lab Invest, 94 (9): 950-65. [PMID:25068660]