Trpc ion channel inhibitors for use in therapy

US20200345741A1Inactive Publication Date: 2020-11-05UNIV OF LEEDS
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  • Trpc ion channel inhibitors for use in therapy
  • Trpc ion channel inhibitors for use in therapy
  • Trpc ion channel inhibitors for use in therapy

Examples

Experimental program
Comparison scheme
Effect test

example 1

dy Weight on Chow Diet

[0284]Body weight and Subcutaneous white adipose tissue (scWAT) fat pad weight were measured in C4WT (wildtype litter-mate controls for TRPC4 knockout mice), C5WT (wildtype litter-mate controls for TRPC5 knockout mice), C4KO (TRPC4 knockout mice) and C5KO (TRPC5 knockout mice) (n=6).

[0285]C4KO and C5KO mice on chow diet were apparently normal, showing no difference in body weight or fat pad weight compared with litter-mate control mice (FIG. 1).

example 2

to Gain Excess Total Body Weight on High Fat Diet

[0286]Mice were next studied on 60% high-fat diet (excess calorie intake). Bodyweights of mice (C4WT, C5WT, C4KO and C5KO) during 8 weeks of diet feeding were measured (n=7-8). Diets were chow (Chow) or 60% high-fat (HFD). Control wildtype (WT) litter-mates (C4WT and C5WT) gained excess total weight as expected during the 8 week experiment period (FIG. 2). C4KO and C5KO mice were, by contrast, strikingly similar to mice on chow diet, showing only normal weight gain as the mice matured (FIG. 2).

example 3

to Gain Excess Fat Pad Weight on High Fat Diet

[0287]Mice were next studied on 60% high-fat diet (excess calorie intake). Subcutaneous white adipose tissue (scWAT) fat pad weights of mice (C4WT, C5WT, C4KO and C5KO) during 8 weeks of diet feeding were measured (n=7-8). Diets were chow (Chow) or 60% high-fat (HFD). Control wildtype (WT) litter-mates (C4WT and C5WT) gained excess fat pad weight as expected during the 8 week experiment period (FIG. 3). C4KO and C5KO mice were, by contrast, strikingly similar to mice on chow diet, showing only normal weight gain as the mice matured (FIG. 3).

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Abstract

Described herein are inhibitors Transient Receptor Potential Canonical (TRPC) ion channels comprising TRPC4 protein and / or TRPC5 protein for use in combating obesity and other medical conditions including insulin resistance associated with Type II diabetes or development of Type II diabetes (pre-diabetes), metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Also disclosed is the use of the inhibitors for cosmetic purposes, such as cosmetic weight loss.

Description

FIELD OF THE INVENTION[0001]The invention relates to direct inhibitors of Transient Receptor Potential Canonical (TRPC) ion channels comprising TRPC4 protein and / or TRPC5 protein as present in adipocytes for use especially in combating obesity (reducing obesity or inhibiting on-set of obesity); this may be for therapeutic purpose or cosmetic weight loss. More particularly, such an inhibitor may target expression or function of TRPC4 and / or TRPC 5 so as to affect ion channel activity or formation. It is envisaged that such use may also extend to the treatment or prophylaxis of insulin resistance associated with Type II diabetes or development of Type II diabetes (pre-diabetes), metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).BACKGROUND OF THE INVENTION[0002]Obesity is now a deadly global pandemic. Worldwide obesity has more than doubled since 1980. In 2014, 39% of adults over 18 were considered overweight and 13% (over 600 millio...

Claims

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Application Information

Patent Timeline
05 Nov 2020
Publication
US20200345741A1
IPC
A61K31/522; A61K31/4184; A61K31/713; A61P3/10; A61P3/04
CPC
A61K31/522; A61P3/04; A61P3/10; A61K31/713; A61K31/4184; C07D235/14; G01N33/6872; G01N2800/042
Inventors
BEECH, DAVID JOHN; FOSTER, RICHARD JAMES