ponazuril   Click here for help

GtoPdb Ligand ID: 12223

Synonyms: ACD-855 | ACD855 | Marquis® (vet use only) | toltrazuril | toltrazuril sulfone
Compound class: Synthetic organic
Comment: Ponazuril is a safe and well tolerated anti-protozoal drug used in horses [2]. Repurposing efforts have identified it as a tropomyosin related kinase (Trk) receptor positive allosteric modulator (PAM), on the hypothesis that increasing NGF/BDNF signalling is predicted to improve neuronal cell functions and survival to boost cognitive capacity in neurological/neurodegenerative diseases. This work by AlzeCure Pharma led to ponazuril's re-naming with their in-house research code ACD855 [1]. ACD855 enhances signalling of the neurotrophins NGF and BDNF via TrkA and TrkB (repectively). It is structurally related to their TrkA-selective lead compound ACD856 that is in clinical development as a novel Alzheimer's disease therapeutic [5].

ACD856's chemical structure has not been disclosed (Oct 2022), but a number of derivatives with the same 1,3,5-triazine scaffold have been claimed as Trk PAMs in AlzeCure patents WO2020002950A1 [3] and WO2018115891A1 [4].
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 CDK toolkit. 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 1
Rotatable bonds 5
Topological polar surface area 128.09
Molecular weight 457.38
XLogP 4
No. Lipinski's rules broken 0
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.

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Canonical SMILES Cc1cc(ccc1Oc1ccc(cc1)S(=O)(=O)C(F)(F)F)n1c(=O)[nH]c(=O)n(c1=O)C
Isomeric SMILES Cc1c(ccc(c1)n1c(=O)[nH]c(=O)n(c1=O)C)Oc1ccc(cc1)S(=O)(=O)C(F)(F)F
InChI InChI=1S/C18H14F3N3O6S/c1-10-9-11(24-16(26)22-15(25)23(2)17(24)27)3-8-14(10)30-12-4-6-13(7-5-12)31(28,29)18(19,20)21/h3-9H,1-2H3,(H,22,25,26)
InChI Key VBUNOIXRZNJNAD-UHFFFAOYSA-N
Bioactivity Comments
ACD855 enhances TrkA and TrkB signalling (NGF- or BDNF-mediated respectively), but does not alter signalling via TrkC, IGF1R or FGFR1 [1]. In vitro ACD855 enhances NGF/TrkA activity to ~140% compared to control (EC50 1.9 μM), and BDNF/TrkB signalling to ~300% of control (EC50 3.2 μM).
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
neurotrophic receptor tyrosine kinase 1 Hs Allosteric modulator Positive - - - 1
⤷ [1]