Delving into the Latest Updates on Trino Therapeutics Ltd. with Synapse

概览

疾病领域	数量

免疫系统疾病	1

排名前五的药物类型	数量

小分子化药	2

关联

3

项与 Trino Therapeutics Ltd. 相关的药物

PH-5 (Trino Therapeutics)

靶点-

作用机制-

在研机构

Trino Therapeutics Ltd.

原研机构

Trino Therapeutics Ltd.

在研适应症

炎症性肠病 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

PH-44

靶点-

作用机制-

在研机构

Trino Therapeutics Ltd.

原研机构

Trino Therapeutics Ltd.

在研适应症

炎症性肠病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

PH-46A

靶点-

作用机制

肥大细胞稳定剂

在研机构-

原研机构

Trino Therapeutics Ltd.

在研适应症-

非在研适应症

溃疡性结肠炎

最高研发阶段无进展

首次获批国家/地区-

首次获批日期-

1

项与 Trino Therapeutics Ltd. 相关的临床试验

ISRCTN90725219 / Completed临床1期

A Phase I, prospective, double-blind, randomised, placebo-controlled, dose escalating study to assess the safety and tolerability of single and multiple oral doses of PH46A and the effect of the fasted and fed state on pharmacokinetics of PH46A in healthy volunteers

开始日期2014-02-07

申办/合作机构

Trino Therapeutics Ltd.

100 项与 Trino Therapeutics Ltd. 相关的临床结果

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0 项与 Trino Therapeutics Ltd. 相关的专利（医药）

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3

项与 Trino Therapeutics Ltd. 相关的文献（医药）

2020-02-01·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

作者: 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.

2015-03-01·Journal of Molecular Structure3区 · 化学

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

3区 · 化学

Article

作者: 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.

Molecules3区 · 化学

Bioactive Indanes: Proof of Concept Study for Enantioselective Synthetic Routes to PH46A, a New Potential Anti-Inflammatory Agent

3区 · 化学

ArticleOA

作者: Scalabrino, Gaia ; Sheridan, Helen ; Frankish, Neil ; Zhang, Tao

PH46A is a single enantiomer and a member of the 1,2-indane dimer family. It has two contiguous stereogenic centers with S,S configurations, one of which being a quaternary center, which has been developed as a clinical candidate for the treatment of inflammatory and autoimmune conditions. The current synthetic route to PH46A involves the generation of an unwanted enantiomer (R,R)-7, thus reducing the final yield significantly. Therefore, we have investigated potential alternatives to improve the efficiency of this synthesis. The first phase of the study has demonstrated proof of principle for a chiral alkylation of ketone 3 using phase-transfer catalysis, providing a key intermediate ketone (S)-4. The parent alkaloids required for the synthesis of PH46A, quinine or cinchonidine, have also been identified. Promising enantiomeric excesses of up to 50% have been achieved to date, and the use of an alternative substrate, unsaturated ketone 9, has also opened up further avenues for optimisation in future studies. The second part of the study involved preliminary screening the effects of a panel of hydrolase enzymes on (rac)-4 in order to identify a potential chemo-enzymatic route to optimise the introduction of chirality into PH46A at early stage of the synthesis. The hydrolase module has also yielded positive results; enzyme AH-46 with MtBE providing a selectivity factor of 8.4 with enantiomeric excess of 77%. Overall, positive results were obtained in this proof of concept study described herein. It is believed that conditions of both chiral PTC alkylation and biocatalytic hydrolysis could be optimised to further enhance the selectivity and improve the overall yield. This work is currently ongoing.

100 项与 Trino Therapeutics Ltd. 相关的药物交易

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100 项与 Trino Therapeutics Ltd. 相关的转化医学

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