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DF-003   Click here for help

GtoPdb Ligand ID: 14505

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: DF-003 is an orally hbioactive alpha kinase 1 (ALPK1) inhibitor [1].

The rare genetic autoinflammatory condition known as retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache (ROSAH) syndrome is caused by activating mutations in ALPK1. DF-003 was designed as a disease modifying therapy to directly target the hyperactive ALPK1.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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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 5
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 82.03
Molecular weight 486.97
XLogP 2.91
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[C@@](C)(C1=CC=C(C=C1)Cl)C2=CSC(=N2)NC(=O)C3=C(C=C(C=C3F)N4CCNCC4)F
Isomeric SMILES C[C@@](C#C)(C1=CSC(NC(=O)C2=C(F)C=C(C=C2F)N3CCNCC3)=N1)C4=CC=C(Cl)C=C4
InChI InChI=1S/C24H21ClF2N4OS/c1-3-24(2,15-4-6-16(25)7-5-15)20-14-33-23(29-20)30-22(32)21-18(26)12-17(13-19(21)27)31-10-8-28-9-11-31/h1,4-7,12-14,28H,8-11H2,2H3,(H,29,30,32)/t24-/m0/s1
InChI Key ANRFSQHHAOCNIN-DEOSSOPVSA-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
DF-003 was progressed as a clinical candidate for the treatment of ROSAH syndrome. It was granted FDA orphan drug designation in March 2026 for this indication [2].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT05997641 Evaluating the Safety, Tolerability, and Pharmacokinetics of DF-003 in Healthy Subjects Phase 1 Interventional Shanghai Yao Yuan Biotechnology Ltd. (also known as Drug Farm)
NCT06395285 Evaluating the Safety and Tolerability of Orally Administered DF-003 in ROSAH Syndrome Patients Phase 1 Interventional Shanghai Yao Yuan Biotechnology Ltd. (also known as Drug Farm)