ACT001   Click here for help

GtoPdb Ligand ID: 13291

Synonyms: ACT-001
Compound class: Synthetic organic
Comment: ACT001 inhibits PD-L1 expression in neutrophils, and releases immune system suppression by the PD-1/PD-L1 checkpoint. It has potent anticancer and anti-inflammatory activities, and can cross the blood-brain barrier. The molecular mechanism of ACT001 is reported to involve direct interaction with the STAT3 transcription factor and inhibition of STAT3 phosphorylation [3,5]. In cancers that overexpress PD-L1 and escape immune surveillance, this offers a therapeutic strategy to enhance anti-tumour immune response. Some microbial pathogens upregulate PD-L1 expression in their hosts as a mechanism to negatively regulate the host anti-pathogen immune response [1-2,4,6-7]. By blocking PD-L1 expression ACT001 has been shown effective against systemic C. albicans infection [7]. However ACT001's high CNS permeability and strong cytotoxicity limit its use in the treatment of microbial infections. A sulphide ACT001 prodrug with an improved safety profile has been designed [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 4
Hydrogen bond donors 1
Rotatable bonds 2
Topological polar surface area 49.77
Molecular weight 293.4
XLogP 0.84
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 CC1=C2CC[C@](C)([C@]2([H])[C@@H]3[C@@H](CC1)[C@H](CN(C)C)C(=O)O3)O
Isomeric SMILES [H][C@@]12[C@H]3OC(=O)[C@@H](CN(C)C)[C@@H]3CCC(C)=C1CC[C@@]2(C)O
InChI InChI=1S/C17H27NO3/c1-10-5-6-12-13(9-18(3)4)16(19)21-15(12)14-11(10)7-8-17(14,2)20/h12-15,20H,5-9H2,1-4H3/t12-,13-,14-,15-,17+/m0/s1
InChI Key ZPBIJIIQXPRJSS-WNZSCWOMSA-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/)
No information available.
Summary of Clinical Use Click here for help
ACT001 was a clinical candidate for advanced glioblastoma multiforme, and the FDA had designated it (as dimethylaminomicheliolide fumarate) as an orphan drug for this indication in early 2022.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT05053880 A Study to Evaluate Safety and Efficacy of ACT001 and Anti-PD-1 in Patients With Surgically Accessible Recurrent Glioblastoma Multiforme Phase 1/Phase 2 Interventional Accendatech USA Inc.