Namodenoson

Last updated
Namodenoson
Namodenoson.svg
Clinical data
Other namesChloro-IB-MECA; 2-Cl-IB-MECA
Legal status
Legal status
  • Investigational
Identifiers
  • (2S,3S,4R,5R)-5-[2-Chloro-6-[(3-iodophenyl)methylamino]purin-9-yl]-3,4-dihydroxy-N-methyloxolane-2-carboxamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.162.091 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C18H18ClIN6O4
Molar mass 544.73 g·mol−1
3D model (JSmol)
  • CNC(=O)[C@@H]1[C@H]([C@H]([C@@H](O1)N2C=NC3=C(N=C(N=C32)Cl)NCC4=CC(=CC=C4)I)O)O
  • InChI=1S/C18H18ClIN6O4/c1-21-16(29)13-11(27)12(28)17(30-13)26-7-23-10-14(24-18(19)25-15(10)26)22-6-8-3-2-4-9(20)5-8/h2-5,7,11-13,17,27-28H,6H2,1H3,(H,21,29)(H,22,24,25)/t11-,12+,13-,17+/m0/s1
  • Key:IPSYPUKKXMNCNQ-PFHKOEEOSA-N

Namodenoson is a small molecule A3 adenosine receptor (A3AR) agonist. It is developed by Can-Fite for non-alcoholic fatty liver disease, [1] liver cancer, [2] and pancreatic cancer. [3]

Related Research Articles

<span class="mw-page-title-main">Hepatitis</span> Inflammation of the liver

Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea. Hepatitis is acute if it resolves within six months, and chronic if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer.

<span class="mw-page-title-main">Hepatocellular carcinoma</span> Medical condition

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.

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

Everolimus, sold under the brand name Afinitor among others, is a medication used as an immunosuppressant to prevent rejection of organ transplants and as a targeted therapy in the treatment of renal cell cancer and other tumours.

<span class="mw-page-title-main">Klatskin tumor</span> Medical condition

A Klatskin tumor is a cholangiocarcinoma occurring at the confluence of the right and left hepatic bile ducts. The disease was named after Gerald Klatskin, who in 1965 described 15 cases and found some characteristics for this type of cholangiocarcinoma

<span class="mw-page-title-main">Liver disease</span> Medical condition

Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.

<span class="mw-page-title-main">Fatty liver disease</span> Medical condition related to obesity

Fatty liver disease (FLD), also known as hepatic steatosis and steatotic liver disease (SLD), is a condition where excess fat builds up in the liver. Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen. Complications may include cirrhosis, liver cancer, and esophageal varices.

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

Silibinin (INN), also known as silybin (both from Silybum, the generic name of the plant from which it is extracted), is the major active constituent of silymarin, a standardized extract of the milk thistle, containing a mixture of flavonolignans consisting of silibinin, isosilibinin, silychristin, silidianin, and others. Silibinin itself is a mixture of two diastereomers, silybin A and silybin B, in approximately equimolar ratio. Silibinin is used in pure forms as a medication, and more frequently as an active ingredient in milk thistle–derived herbal supplements.

<span class="mw-page-title-main">Liver biopsy</span>

Liver biopsy is the biopsy from the liver. It is a medical test that is done to aid diagnosis of liver disease, to assess the severity of known liver disease, and to monitor the progress of treatment.

<span class="mw-page-title-main">Alcohol and cancer</span> Relationship between cancer and the consumption of alcohol

Alcohol causes cancers of the oesophagus, liver, breast, colon, oral cavity, rectum, pharynx, and larynx, and probably causes cancers of the pancreas. Consumption of alcohol in any quantity can cause cancer. The more alcohol is consumed, the higher the cancer risk, and no amount can be considered safe. Alcoholic beverages were classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC) in 1988.. An estimated 3.6% of all cancer cases and 3.5% of cancer deaths worldwide are attributable to consumption of alcohol. 740,000 cases of cancer in 2020 or 4.1% of new cancer cases were attributed to alcohol.

Chronic liver disease in the clinical context is a disease process of the liver that involves a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis. "Chronic liver disease" refers to disease of the liver which lasts over a period of six months. It consists of a wide range of liver pathologies which include inflammation, liver cirrhosis, and hepatocellular carcinoma. The entire spectrum need not be experienced.

<span class="mw-page-title-main">Cahill cycle</span> Metabolic pathway for transport of energy into and removal of ammonia from muscles

The Cahill cycle, also known as the alanine cycle or glucose-alanine cycle, is the series of reactions in which amino groups and carbons from muscle are transported to the liver. It is quite similar to the Cori cycle in the cycling of nutrients between skeletal muscle and the liver. When muscles degrade amino acids for energy needs, the resulting nitrogen is transaminated to pyruvate to form alanine. This is performed by the enzyme alanine transaminase (ALT), which converts L-glutamate and pyruvate into α-ketoglutarate and L-alanine. The resulting L-alanine is shuttled to the liver where the nitrogen enters the urea cycle and the pyruvate is used to make glucose.

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

Steatohepatitis is a type of fatty liver disease, characterized by inflammation of the liver with concurrent fat accumulation in liver. Mere deposition of fat in the liver is termed steatosis, and together these constitute fatty liver changes.

<span class="mw-page-title-main">Metabolic dysfunction–associated steatotic liver disease</span> Excessive fat buildup in the liver with other metabolic disease

Metabolic dysfunction–associated steatotic liver disease (MASLD) is the name adopted in 2023 for the condition previously known as non-alcoholic fatty liver disease (NAFLD). This condition is diagnosed when there is excessive fat build-up in the liver, and at least one metabolic risk factor. When there is also moderate alcohol use, the term MetALD is used, and these are differentiated from alcoholic liver disease (ALD) when this is the sole cause of steatotic liver disease. The terms non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis have been used to describe different severities, the latter indicating the presence of further liver inflammation. NAFL is less dangerous than NASH and usually does not progress to it, but this progression may eventually lead to complications, such as cirrhosis, liver cancer, liver failure, and cardiovascular disease.

<span class="mw-page-title-main">Sanford Burnham Prebys Medical Discovery Institute</span> Non-profit medical research institute

Sanford Burnham Prebys is a 501(c)(3) non-profit medical research institute focusing on basic and translational research, with major research programs in cancer, neurodegeneration, diabetes, infectious, inflammatory, and childhood diseases. The institute also specializes in stem cell research and drug discovery technologies.

<span class="mw-page-title-main">Liver cancer</span> Medical condition

Liver cancer is cancer that starts in the liver. Liver cancer can be primary or secondary. Liver metastasis is more common than that which starts in the liver. Instances of liver cancer are increasing globally.

<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.

Ramucirumab is a fully human monoclonal antibody (IgG1) developed for the treatment of solid tumors. This drug was developed by ImClone Systems Inc. It was isolated from a native phage display library from Dyax.

<span class="mw-page-title-main">Cirrhosis</span> Chronic disease of the liver, characterized by fibrosis

Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage to the liver leads to repair of liver tissue and subsequent formation of scar tissue. Over time, scar tissue can replace normal functioning tissue, leading to the impaired liver function of cirrhosis. The disease typically develops slowly over months or years. Early symptoms may include tiredness, weakness, loss of appetite, unexplained weight loss, nausea and vomiting, and discomfort in the right upper quadrant of the abdomen. As the disease worsens, symptoms may include itchiness, swelling in the lower legs, fluid build-up in the abdomen, jaundice, bruising easily, and the development of spider-like blood vessels in the skin. The fluid build-up in the abdomen may develop into spontaneous infections. More serious complications include hepatic encephalopathy, bleeding from dilated veins in the esophagus, stomach, or intestines, and liver cancer.

In molecular biology mir-216 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

<span class="mw-page-title-main">Metadoxine</span> Medication used for alcohol intoxication

Metadoxine, also known as pyridoxine-pyrrolidone carboxylate, is a drug used to treat chronic and acute alcohol intoxication. Metadoxine accelerates alcohol clearance from the blood.

References

  1. Safadi, Rifaat; Braun, Marius; Francis, Adi; Milgrom, Yael; Massarwa, Muhammad; Hakimian, David; Hazou, Wadi; Issachar, Assaf; Harpaz, Zivit; Farbstein, Motti; Itzhak, Inbal; Lev-Cohain, Naama; Bareket-Samish, Avital; Silverman, Michael H.; Fishman, Pnina (December 2021). "Randomised clinical trial: A phase 2 double-blind study of namodenoson in non-alcoholic fatty liver disease and steatohepatitis". Alimentary Pharmacology & Therapeutics. 54 (11–12): 1405–1415. doi:10.1111/apt.16664. ISSN   1365-2036. PMC   9298378 . PMID   34671996.
  2. Stemmer, Salomon M.; Manojlovic, Nebojsa S.; Marinca, Mihai Vasile; Petrov, Petar; Cherciu, Nelly; Ganea, Doina; Ciuleanu, Tudor Eliade; Pusca, Ioana Adriana; Beg, Muhammad Shaalan; Purcell, William T.; Croitoru, Adina-Emilia; Ilieva, Rumyana Nedyalkova; Natošević, Sladjana; Nita, Amedeia Lavinir; Kalev, Dimitar Nikolaev; Harpaz, Zivit; Farbstein, Motti; Silverman, Michael H.; Bristol, David; Itzhak, Inbal; Fishman, Pnina (7 January 2021). "Namodenoson in Advanced Hepatocellular Carcinoma and Child–Pugh B Cirrhosis: Randomized Placebo-Controlled Clinical Trial". Cancers. 13 (2): 187. doi: 10.3390/cancers13020187 . ISSN   2072-6694. PMC   7825785 . PMID   33430312.
  3. Fishman, Pnina; Bareket-Samish, Avital; Itzhak, Inbal (1 June 2023). "Effects of namodenoson on pancreatic carcinoma: Preclinical evidence". Journal of Clinical Oncology. 41 (16_suppl): e15134. doi:10.1200/JCO.2023.41.16_suppl.e15134. S2CID   259081369.