February 08, 2024 15:03 / Last edited by ilitarul1979 6 months ago
Sobetirome, also known as GC-1 and QRX-431, is a member of a class of compounds known as selective thyromimetics (Scanlan et al. , Curr Opin Drug Discov Dev 4:614-622). These compounds are synthetic structural analogs of thyroid hormone that have tissue-specific thyroid hormone actions. ->
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Sobetirome (GC-1) is a thyroid hormone receptor β (TRβ)- and liver uptake-selective agonist. Sobetirome (48 nmol/kg) reduces high-density lipoprotein (HDL) cholesterol and very low-density lipoprotein (VLDL) triglyceride levels in euthyroid Mice. Sobetirome reduces HDL cholesterol and triglyceride Levels in hypercholesterolemic mice. Sobetirome increases hepatic HDL receptors and stimulates .
INTRODUCTION CHRISTOPHER J. LAING, NANCY E. COOKE, in Vitamin D (Second Edition), 2005 C. Polymorphisms of DBP/Gc-Globulin Protein and Gene DBP (or group-specific component, Gc) was originally characterized in humans by serum electrophoresis as the product of two autosomal, codominant alleles (Gc 1 and Gc 2 ).
The Thyromimetic Sobetirome (GC-1) Alters Bile Acid Metabolism in a Mouse Model of Hepatic Cholestasis Chronic cholestasis results from bile secretory defects or impaired bile flow with few effective medical therapies available.
Therefore, analogues with TRβ selectivity were developed, and four different compounds have been used in clinical trials: GC-1 (sobetirome), KB-2115 (eprotirome), MB07344/VK2809, and MGL-3196 (resmetirom).
GC-1 is being tested in clinical trials for lowering cholesterol, under the name sobetirome. However, Phillips said the doses of sobetirome used in the cholesterol-lowering studies are much lower than what would be needed for weight loss.
Sobetirome (GC-1) is a thyromimetic drug that binds to the thyroid hormone receptor TRβ1 preferentially compared to TRα1. It has been investigated for the treatment of dyslipidemia, obesity, [1] Pitt-Hopkins syndrome, [2] cholestatic liver disease, [3] multiple sclerosis, [4] bleomycin -induced lung fibrosis, [5] and COVID-19 caused ARDS. [6]
In GC-1, now called sobetirome, the iodine atoms and the oxygen linking the two aromatic rings are replaced by alkyl groups, and the amino acid side chain is replaced by an oxoacetic chain. The ratio of TRβ to TRα affinity is 10-fold higher for GC-1 than for T3, and an additional useful property is represented by selective liver uptake.
GC-1 (or sobetirome; Table Table1) 1) is one of the first compounds designed in a series of analogues, with, amongst others, a 3′-isopropyl substitution at the distal phenyl ring of the molecule (instead of iodine in T 3). GC-1 has at least a ~3-18-fold selectivity for TRβ over TRα [16, 27].
Sobetirome (GC-1) and subsequently Eprotirome (KB2115) were the first examples of TRβ selective thyromimetics, with Sobetirome differing from the structure of thyronines because of the absence of halogens, biaryl ether oxygen, and amino-acidic side chain.
Sobetirome (GC-1) and subsequently Eprotirome (KB2115) were the first examples of TRβ selective thyromimetics, with Sobetirome differing from the structure of thyronines because of the absence of halogens, biaryl ether oxygen, and amino-acidic side chain. Even though both thyromimetics showed encouraging actions against hypercholesterolemia .
Our objective was to assess the sustained, low-dose and constant administration of the thyroid receptor-β (TRβ)-selective agonist GC-1 (sobetirome) from a novel nanochannel membrane device (NMD).
2. 2 Sobetirome Sobetirome (GC-1) was the first of a new class of thyromi-metics that emerged in the 1990s [4-6]. GC-1 binds preferen-tially to TRb versus TRa and accumulates selectively in liver. Sobetirome hasbeen tested extensivelyin preclinical ani-mal models, including rodents and primates, and reached Phase Ib human clinical trials.
Sobetirome (GC-1) is currently being investigated as a therapy for a range of neurological diseases . Few thyromimetics partition to the central nervous system, so it is critical to understand its distribution, so a robust and reproducible bioanalytical technique is necessary to probe its pharmacokinetic properties. Optimized extraction .
Unfortunately, these therapeutically desirable effects are associated to a thyrotoxic state, which includes induction of tachycardia, arrhythmia, muscle catabolism, reduced bone mineralization, alteration of central nervous system (CNS) development, and mood disorders 1,4-6. Such adverse effects strongly limit the use of THs.
GC-1; KB2115; cholesterol lowering; dyslipidemia; eprotirome; obesity; sobetirome; thyroid hormone; thyroid hormone receptors; thyromimetic. Research Support, N. I. H. , Extramural Acetates / adverse effects Acetates / pharmacology* Cardiovascular Diseases / drug therapy* Clinical Trials as Topic Dyslipidemias / drug therapy* Phenols / adverse effects
In GC-1, now called sobetirome, the iodine atoms and the oxygen linking the two aromatic rings are replaced by alkyl groups, and the amino acid side chain is replaced by an oxoacetic chain. The ratio of TRβ to TRα affinity is 10-fold higher for GC-1 than for T3, and an additional useful property is represented by selective liver uptake.
2. 2 Sobetirome. Sobetirome (GC-1) was the first of a new class of thyromimetics that emerged in the 1990s [Citation 4-Citation 6]. GC-1 binds preferentially to TRβ versus TRα and accumulates selectively in liver. Sobetirome has been tested extensively in preclinical animal models, including rodents and primates, and reached Phase Ib human .
Sobetirome (GC-1) Sobetirome (3,5-Dimethyl-4(4′-hydroxy-3′-isopropylbenzyl) phenoxy) acetic acid) was developed in the late 1990s and was initially shown in hypothyroid mice to reduce cholesterol levels back to normal euthyroid levels .
The present review will discuss the recent patents applied for sobetirome (GC-1), which set the course for the establishment of a novel approach to lower plasma cholesterol and triglycerides.
What is GC-1 and what does it do? Thyroid hormone regulates the metabolism of food and controls our body's ability to burn off fat. GC-1 is also known as Sobetirome. This research chemical is a thyroid hormone receptor agonist. Also known as a thyromimetic, it mimics thyroid hormone without actually being a hormone.
GC-1 (sobetirome) was purchased from Tocris (Bristol, UK). The estimated drug release from the nanochannel capsules in vivo was determined to be 27. 5±6. 8 μgperday.