Asengeprast

Last updated

Asengeprast
Asengeprast.svg
Chemical structure of asengeprast (FT011)
Clinical data
Other namesFT011
Identifiers
  • 2-[[(E)-3-(3-methoxy-4-prop-2-ynoxyphenyl)prop-2-enoyl]amino]benzoic acid
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C20H17NO5
Molar mass 351.358 g·mol−1
3D model (JSmol)
  • COC1=C(C=CC(=C1)/C=C/C(=O)NC2=CC=CC=C2C(=O)O)OCC#C
  • InChI=InChI=1S/C20H17NO5/c1-3-12-26-17-10-8-14(13-18(17)25-2)9-11-19(22)21-16-7-5-4-6-15(16)20(23)24/h1,4-11,13H,12H2,2H3,(H,21,22)(H,23,24)/b11-9+
  • Key:UIWZIDIJCUEOMT-PKNBQFBNSA-N

Asengeprast (development code FT011) is an experimental scleroderma drug candidate. [1] It is a small molecule inhibitor of the G-protein coupled receptor GPR68 with antifibrotic activity. [2] It is being developed by Certa Therapeutics.

The European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) has granted orphan drug status to FT011, for systemic sclerosis (SSc). [3]

Asengeprast has been reported to attenuate fibrosis and chronic heart failure in experimental diabetic cardiomyopathy. [4] Asengeprast can also inhibit kidney fibrosis and prevent kidney failure. [5] It was developed by structure-activity optimization of the antifibrotic activity of cinnamoyl anthranilates, by assessment of their ability to prevent TGF-beta-stimulated production of collagen. [6]

See also

Related Research Articles

<span class="mw-page-title-main">ACE inhibitor</span> Class of medications used primarily to treat high blood pressure

Angiotensin-converting-enzyme inhibitors are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart.

<span class="mw-page-title-main">Systemic scleroderma</span> Accumulation of collagen in the skin and internal organs

Systemic scleroderma, or systemic sclerosis, is an autoimmune rheumatic disease characterised by excessive production and accumulation of collagen, called fibrosis, in the skin and internal organs and by injuries to small arteries. There are two major subgroups of systemic sclerosis based on the extent of skin involvement: limited and diffuse. The limited form affects areas below, but not above, the elbows and knees with or without involvement of the face. The diffuse form also affects the skin above the elbows and knees and can also spread to the torso. Visceral organs, including the kidneys, heart, lungs, and gastrointestinal tract can also be affected by the fibrotic process. Prognosis is determined by the form of the disease and the extent of visceral involvement. Patients with limited systemic sclerosis have a better prognosis than those with the diffuse form. Death is most often caused by lung, heart, and kidney involvement. The risk of cancer is increased slightly.

<span class="mw-page-title-main">Angiotensin II receptor blocker</span> Group of pharmaceuticals that modulate the renin–angiotensin system

Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals that bind to and inhibit the angiotensin II receptor type 1 (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system.

<span class="mw-page-title-main">Fibrosis</span> Excess connective tissue in healing

Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of permanent scar tissue.

<span class="mw-page-title-main">Amiloride</span> Medication

Amiloride, sold under the trade name Midamor among others, is a medication typically used with other medications to treat high blood pressure or swelling due to heart failure or cirrhosis of the liver. Amiloride is classified as a potassium-sparing diuretic. Amiloride is often used together with another diuretic, such as a thiazide or loop diuretic. It is taken by mouth. Onset of action is about two hours and it lasts for about a day.

<span class="mw-page-title-main">Candesartan</span> Angiotensin II receptor antagonist

Candesartan is an angiotensin receptor blocker used mainly for the treatment of high blood pressure and congestive heart failure. Candesartan has a very low maintenance dose. Like olmesartan, the metabolism of the drug is unusual as it is a cascading prodrug. Candesartan has good bioavailibility and is the most potent by weight of the AT-1 receptor antagonists.

<span class="mw-page-title-main">Pulmonary fibrosis</span> Disease that causes scarring of the lungs

Pulmonary fibrosis is a condition in which the lungs become scarred over time. Symptoms include shortness of breath, a dry cough, feeling tired, weight loss, and nail clubbing. Complications may include pulmonary hypertension, respiratory failure, pneumothorax, and lung cancer.

<span class="mw-page-title-main">Benazepril</span> Medication used to treat high blood pressure and heart failure

Benazepril, sold under the brand name Lotensin among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combinations benazepril/hydrochlorothiazide and benazepril/amlodipine.

Loeffler endocarditis is a form of heart disease characterized by a stiffened, poorly-functioning heart caused by infiltration of the heart by white blood cells known as eosinophils. Restrictive cardiomyopathy is a disease of the heart muscle which results in impaired diastolic filling of the heart ventricles, i.e. the large heart chambers which pump blood into the pulmonary or systemic circulation. Diastole is the part of the cardiac contraction-relaxation cycle in which the heart fills with venous blood after the emptying done during its previous systole.

Cardiac fibrosis commonly refers to the excess deposition of extracellular matrix in the cardiac muscle, but the term may also refer to an abnormal thickening of the heart valves due to inappropriate proliferation of cardiac fibroblasts. Fibrotic cardiac muscle is stiffer and less compliant and is seen in the progression to heart failure. The description below focuses on a specific mechanism of valvular pathology but there are other causes of valve pathology and fibrosis of the cardiac muscle.

Sulodexide, traded as Aterina, is a highly purified mixture of glycosaminoglycans composed of heparan sulfate (80%) and dermatan sulfate (20%).

<span class="mw-page-title-main">Free fatty acid receptor 1</span> Protein-coding gene in the species Homo sapiens

Free fatty acid receptor 1 (FFAR1), also known as G-protein coupled receptor 40 (GPR40), is a rhodopsin-like G-protein coupled receptor that is coded by the FFAR1 gene. This gene is located on the short arm of chromosome 19 at position 13.12. G protein-coupled receptors reside on their parent cells' surface membranes, bind any one of the specific set of ligands that they recognize, and thereby are activated to trigger certain responses in their parent cells. FFAR1 is a member of a small family of structurally and functionally related GPRs termed free fatty acid receptors (FFARs). This family includes at least three other FFARs viz., FFAR2, FFAR3, and FFAR4. FFARs bind and thereby are activated by certain fatty acids.

<span class="mw-page-title-main">Diabetic cardiomyopathy</span> Medical condition

Diabetic cardiomyopathy is a disorder of the heart muscle in people with diabetes. It can lead to inability of the heart to circulate blood through the body effectively, a state known as heart failure(HF), with accumulation of fluid in the lungs or legs. Most heart failure in people with diabetes results from coronary artery disease, and diabetic cardiomyopathy is only said to exist if there is no coronary artery disease to explain the heart muscle disorder.

<span class="mw-page-title-main">Leonurine</span> Chemical compound

Leonurine is a pseudoalkaloid that has been isolated from Leonotis leonurus, Leonotis nepetifolia, Leonurus japonicus, Leonurus cardiaca (motherwort), Leonurus sibiricus, as well as other plants of family Lamiaceae. Leonurine is easily extracted into water.

<span class="mw-page-title-main">Scleroderma</span> Group of autoimmune diseases resulting in abnormal growth of connective tissue

Scleroderma is a group of autoimmune diseases that may result in changes to the skin, blood vessels, muscles, and internal organs. The disease can be either localized to the skin or involve other organs, as well. Symptoms may include areas of thickened skin, stiffness, feeling tired, and poor blood flow to the fingers or toes with cold exposure. One form of the condition, known as CREST syndrome, classically results in calcium deposits, Raynaud's syndrome, esophageal problems, thickening of the skin of the fingers and toes, and areas of small, dilated blood vessels.

<span class="mw-page-title-main">Pirfenidone</span> Chemical compound

Pirfenidone, sold under the brand name Pirespa among others, is a medication used for the treatment of idiopathic pulmonary fibrosis. It works by reducing lung fibrosis through downregulation of the production of growth factors and procollagens I and II.

<span class="mw-page-title-main">Chrysophanol</span> Chemical compound

Chrysophanol, also known as chrysophanic acid, is a fungal isolate and a natural anthraquinone. It is a C-3 methyl substituted chrysazin of the trihydroxyanthraquinone family.

SGLT2 inhibitors are a class of medications that inhibit sodium-glucose transport proteins in the nephron, unlike SGLT1 inhibitors that perform a similar function in the intestinal mucosa. The foremost metabolic effect of this is to inhibit reabsorption of glucose in the kidney and therefore lower blood sugar. They act by inhibiting sodium/glucose cotransporter 2 (SGLT2). SGLT2 inhibitors are used in the treatment of type 2 diabetes. Apart from blood sugar control, gliflozins have been shown to provide significant cardiovascular benefit in people with type 2 diabetes. As of 2014, several medications of this class had been approved or were under development. In studies on canagliflozin, a member of this class, the medication was found to enhance blood sugar control as well as reduce body weight and systolic and diastolic blood pressure.

<span class="mw-page-title-main">Setanaxib</span> Chemical compound

Setanaxib is an experimental orally bioavailable dual inhibitor of NADPH oxidase isoforms NOX4 and NOX1. Setanaxib is a member of the pyrazolopyridine dione chemical series. The compound is the only specific NOX inhibitor that has entered into clinical trials.

<span class="mw-page-title-main">Zevaquenabant</span> Chemical compound

Zevaquenabant is an investigational small-molecule drug, discovered by Dr George Kunos, Dr Resat Cinar, and Dr Malliga iyer at the National Institutes of Health. Zevaquenabant was described as a third generation cannabinoid receptor 1 (CB1R) antagonist due to its peripheral selectivity and polypharmacology. It acts as a peripherally selective inverse agonist of the cannabinoid receptor 1 and an inducible nitric oxide synthase (iNOS) inhibitor. It has been studied in the experimental models of fibrotic disorders such as liver fibrosis[1], chronic kidney disease, idiopathic pulmonary fibrosis, Hermansky-Pudlak syndrome pulmonary fibrosis, skin fibrosis, and metabolic disorders such as obesity[2] and dyslipidemia.

References

  1. "Asengeprast Ligand page". IUPHAR/BPS Guide to PHARMACOLOGY.
  2. "Certa Therapeutics website".
  3. Inácio P (23 July 2024). "Certa's FT011 granted orphan drug status in Europe for SSc". Scleroderma News.
  4. Zhang Y, Edgley AJ, Cox AJ, Powell AK, Wang B, Kompa AR, et al. (May 2012). "FT011, a new anti-fibrotic drug, attenuates fibrosis and chronic heart failure in experimental diabetic cardiomyopathy". European Journal of Heart Failure. 14 (5): 549–562. doi:10.1093/eurjhf/hfs011. PMID   22417655.
  5. Gilbert RE, Zhang Y, Williams SJ, Zammit SC, Stapleton DI, Cox AJ, et al. (2012). "A purpose-synthesised anti-fibrotic agent attenuates experimental kidney diseases in the rat". PLOS ONE. 7 (10): e47160. Bibcode:2012PLoSO...747160G. doi: 10.1371/journal.pone.0047160 . PMC   3468513 . PMID   23071743.
  6. Zammit SC, Cox AJ, Gow RM, Zhang Y, Gilbert RE, Krum H, et al. (December 2009). "Evaluation and optimization of antifibrotic activity of cinnamoyl anthranilates". Bioorganic & Medicinal Chemistry Letters. 19 (24): 7003–7006. doi:10.1016/j.bmcl.2009.09.120. PMID   19879136.