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Overview

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Digestive System Disorders

Immune System Diseases

Respiratory Diseases

Small molecule drug

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Disease Domain	Count

Immune System Diseases	1

Top 5 Drug Type	Count

Small molecule drug	2

The indane scaffold, prevalent in bioactive natural products, underpins numerous therapeutics. Our group developed a series of 1,2-indane dimers, including PH46A (9), for inflammatory and autoimmune diseases. This study details the design, synthesis and characterisation of 21 compounds, including 2,2-disubstituted indanones (16a-16h), indanols (17a-17h), and indanes (18a-18h). These compounds were tested in vitro and in vivo using the murine dextran sulphate sodium (DSS) model of inflammatory bowel disease (IBD). Cytotoxicity screening in THP-1 macrophages and SW480 cells revealed increased cytotoxicity with indene ring substitution at C2, with 18d emerging as potent. In lipoxygenase (LOX) assays, 18a, 18d, and 18c exhibited significant 5-LOX inhibition, with 18d comparable to zileuton. Selective 5-LOX inhibition over 15-LOX indicated distinct ligand-isozyme interactions, potentially informing novel inhibitor development. Cytokine profiling identified compounds with optimal C1 and C2 substituents, particularly 18d, which inhibited IL-6, IL-1β, TNF-α, and IFN-γ in THP-1 macrophages and IL-8 in SW480 cells. In vivo DSS colitis model testing showed significant disease activity index reduction (p < 0.01) with 18d. Subsequent to molecular docking, molecular docking simulations predicted stable binding of 18c and 18d to 5-LOX under mimicked physiological conditions. These findings offer insights into indane-based therapeutic drug development for IBD, highlighting cost reductions by minimising stereochemistry complexity.

01 Feb 2020·Journal of Pharmaceutical and Biomedical Analysis

Bioactive indanes: Development and validation of an LC-MS/MS bioanalytical method for the determination of PH46A, a new potential anti-inflammatory agent, in dog and rat plasma and its application to a pharmacokinetic study in dog

Article

Author: Frankish, Neil ; Scalabrino, Gaia A ; Zhang, Tao ; Sheridan, Helen

A new chemical entity, which is a chiral indane dimer, PH46A, has been developed by our research group. As a clinical candidate. PH46A has recently completed Phase I clinical studies in man. Previously, during its pre-clinical development, in in vivo pre-clinical studies PH46A showed potent anti-inflammatory properties, which can be targeted at a range of diseases, including inflammatory bowel disease (IBD). To support the pre-clinical development of this drug candidate, we developed a LCMS/MS method for determining PH46 (the acid form of PH46A salt) in both dog and rat plasma using Compound 1 as internal standard (IS). Those species were selected for safety pharmacology and toxicology, as well as pharmacokinetics studies. The method was validated over the range 10-10000 ng/mL for both matrices and the linearity, accuracy, precision and specificity over this range were demonstrated to be acceptable. No significant matrix effects or carryover were observed for both PH46 and IS and recovery was consistent. PH46 was found to be stable in both dog and rat plasma under the test conditions, such as at room temperature for >24 h, through 3 freeze/thaw cycles, and at -20 °C for >1 month. PH46 and IS in dog and rat plasma extracts were also found to be stable in the autosampler against fresh standard extracts on re-injection after 143.5 h and 243.5 h, respectively at 4 °C. 10- and 100-fold dilutions with control matrix were found not to affect the performance of the assay. This method was successfully applied to a pharmacokinetic study in the dog. With the exception of one dog, 003 M, oral administration of PH46A in gelatine capsules was well tolerated at a dose level of 100 mg/kg. The highest C_max was observed in animal 003 M. The rapid absorption and high plasma concentration observed for animal 003 M compared to the data for animals 001 M and 002 M may account for the sickness observed in this animal; however, the reasons for this have not been investigated.

01 Mar 2015·Journal of Molecular StructureQ3 · CHEMISTRY

Molecular structure studies of (1S,2S)-2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol

Q3 · CHEMISTRY

Article

Author: Paluch, Krzysztof ; Healy, Anne-Marie ; Scalabrino, Gaia ; Zhang, Tao ; Sheridan, Helen ; Frankish, Neil

The single enantiomer (1S,2S)-2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol (2), has recently been synthesized and isolated from its corresponding diastereoisomer (1). The molecular and crystal structures of this novel compound have been fully analyzed. The relative and absolute configurations have been determined by using a combination of analytical tools including X-ray crystallography, X-ray Powder Diffraction (XRPD) analysis and Nuclear Magnetic Resonance (NMR) spectroscopy.

100 Deals associated with Trino Therapeutics Ltd.

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100 Translational Medicine associated with Trino Therapeutics Ltd.

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Pipeline

Pipeline Snapshot as of 13 Jun 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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1

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

PH-5 (Trino Therapeutics)	Inflammatory Bowel Diseases More	Preclinical
PH-44	Inflammatory Bowel Diseases More	Preclinical
PH-46A	Colitis, Ulcerative More	Pending