Otenaproxesul

Last updated
Otenaproxesul
Otenaproxesul skeletal.svg
Otenaproxesulballstick.png
Clinical data
Other namesATB-352 [1]
Routes of
administration
By mouth
ATC code
  • None
Legal status
Legal status
Identifiers
  • 4-Carbamothioylphenyl (2S)-2-(6-methoxy-2-naphthyl)propanoate
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C21H19NO3S
Molar mass 365.45 g·mol−1
3D model (JSmol)
  • COC1=CC2=CC=C(C=C2C=C1)C(C)C(=O)OC3=CC=C(C=C3)C(N)=S
  • InChI=1S/C21H19NO3S/c1-13(21(23)25-18-8-5-14(6-9-18)20(22)26)15-3-4-17-12-19(24-2)10-7-16(17)11-15/h3-13H,1-2H3,(H2,22,26)/t13-/m0/s1
  • Key:YCNMAPLPQYQJFC-ZDUSSCGKSA-N

Otenaproxesul is a analgesic and anti-inflammatory drug being developed by Antibe Therapeutics. An NSAID structurally derived from naproxen, in 2016 it received approval to commence phase II clinical trials as a treatment for osteoarthritis after completing phase I clinical trials in 2015. [2] In 2018, the drug completed trials for gastrointestinal safety, and in 2020 completed phase IIb trials on efficacy of pain reduction. [3] Initial phase III clinical trials in 2021 failed to meet the necessary criteria to advance to the next phase.

Other in vivo studies have demonstrated a reduction in zymosan-induced pain and inflammation and cytokine-induced bone loss. [4] Preclinical studies have also investigated the treatment of melanoma, intestinal cancer, [5] and periodontitis. [6]

Pharmacology

Like other NSAIDs, otenaproxesul acts as an inhibitor of the cycloxygenase (COX) enzymes, suppressing the production of prostaglandins. Additionally, it releases hydrogen sulfide in the gastrointestinal tract, reducing gastrointestinal adverse effects such as ulcers. [7]

Related Research Articles

<span class="mw-page-title-main">Analgesic</span> Any member of the group of drugs used to achieve analgesia, relief from pain

An analgesic drug, also called simply an analgesic, pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in some instances eliminate, sensation, although analgesia and anesthesia are neurophysiologically overlapping and thus various drugs have both analgesic and anesthetic effects.

<span class="mw-page-title-main">Ketoprofen</span> NSAID analgesic medication

Ketoprofen is one of the propionic acid class of nonsteroidal anti-inflammatory drugs (NSAID) with analgesic and antipyretic effects. It acts by inhibiting the body's production of prostaglandin.

<span class="mw-page-title-main">Nonsteroidal anti-inflammatory drug</span> Class of therapeutic drug for relieving pain and inflammation

Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of use, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.

<span class="mw-page-title-main">Ibuprofen</span> Medication used for treating pain, fever, and inflammation

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arteriosus in a premature baby. It can be used orally or intravenously. It typically begins working within an hour.

<span class="mw-page-title-main">Naproxen</span> Nonsteroidal anti-inflammatory drug (NSAID) used to treat pain

Naproxen, sold under the brand name Aleve among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, inflammatory diseases such as rheumatoid arthritis, gout and fever. It is taken orally. It is available in immediate and delayed release formulations. Onset of effects is within an hour and lasts for up to twelve hours.

Anti-inflammatory or antiphlogistic is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as opposed to opioids, which affect the central nervous system to block pain signaling to the brain.

COX-2 inhibitors (coxibs) are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly target cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration and is the main feature of celecoxib, rofecoxib, and other members of this drug class.

<span class="mw-page-title-main">Diflunisal</span> NSAID analgesic and anti-inflammatory drug

Diflunisal is a salicylic acid derivative with analgesic and anti-inflammatory activity. It was developed by Merck Sharp & Dohme in 1971, as MK647, after showing promise in a research project studying more potent chemical analogs of aspirin. It was first sold under the brand name Dolobid, marketed by Merck & Co., but generic versions are now widely available. It is classed as a nonsteroidal anti-inflammatory drug (NSAID) and is available in 250 mg and 500 mg tablets.

<span class="mw-page-title-main">Deracoxib</span> NSAID analgesic veterinary drug

Deracoxib is a nonsteroidal anti-inflammatory drug (NSAID) of the coxib class, used in dogs to treat pain associated with osteoarthritis, or to prevent pain following orthopedic or dental surgery. It is available as beef-flavored tablets.

<span class="mw-page-title-main">Tolmetin</span> NSAID analgesic medication

Tolmetin is a nonsteroidal anti-inflammatory drug (NSAID) of the heterocyclic acetic acid derivative class.

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

Meclofenamic acid is a drug used for joint, muscular pain, arthritis and dysmenorrhea. It is a member of the anthranilic acid derivatives class of nonsteroidal anti-inflammatory drugs (NSAIDs) and was approved by the US FDA in 1980. Like other members of the class, it is a cyclooxygenase (COX) inhibitor, preventing the formation of prostaglandins.

<span class="mw-page-title-main">Acemetacin</span> NSAID analgesic medication

Acemetacin is a non-steroidal anti-inflammatory drug (NSAID) used for the treatment of osteoarthritis, rheumatoid arthritis, lower back pain, and relieving post-operative pain. It is manufactured by Merck KGaA under the tradename Emflex, and is available in the UK and other countries as a prescription-only drug.

COX-inhibiting nitric oxide donators (CINODs), also known as NO-NSAIDs, are a new class of nonsteroidal anti-inflammatory drug (NSAID) developed with the intention of providing greater safety than existing NSAIDs.

Naproxcinod (nitronaproxen) is a nonsteroidal anti-inflammatory drug (NSAID) developed by the French pharmaceutical company NicOx. It is a derivative of naproxen with a nitroxybutyl ester to allow it to also act as a nitric oxide (NO) donor. This second mechanism of action makes naproxcinod the first in a new class of drugs, the cyclooxygenase inhibiting nitric oxide donators (CINODs), that are hoped to produce similar analgesic efficacy to traditional NSAIDs, but with less gastrointestinal and cardiovascular side effects.

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

Tebanicline is a potent synthetic nicotinic (non-opioid) analgesic drug developed by Abbott. It was developed as a less toxic analog of the potent poison dart frog-derived compound epibatidine, which is about 200 times stronger than morphine as an analgesic, but produces extremely dangerous toxic side effects. Like epibatidine, tebanicline showed potent analgesic activity against neuropathic pain in both animal and human trials, but with far less toxicity than its parent compound. It acts as a partial agonist at neuronal nicotinic acetylcholine receptors, binding to both the α3β4 and the α4β2 subtypes.

<span class="mw-page-title-main">Licofelone</span> Analgesic and anti-inflammatory compound

Licofelone is a dual COX/LOX inhibitor that was studied in clinical trials as a treatment for osteoarthritis and which was under development by Merckle GmbH with partners Alfa Wassermann and Lacer.

John L. Wallace is a medical scientist and was the founder of the Inflammation Research Network at The University of Calgary and inaugural director of the Farncombe Institute at McMaster University. In November 2013, he became the tenth recipient of the Heymans Foundation Memorial Medal. Since its inauguration in 1972, the Medal had been awarded twelve times; six of the recipients are Nobel Laureates. Wallace is also the 2009 recipient of the Premier's Summit Award in Innovation, Canada's largest value research award aimed at supporting the work of an individual scientist.

<span class="mw-page-title-main">Antibe Therapeutics</span> Pharmaceutical corporation

Antibe Therapeutics is a Toronto-based pharmaceutical company that develops pain and inflammation-reducing drugs based on gaseous mediator technology. Antibe was founded by John L. Wallace, also a co-founder of NicOx, the first company to develop drugs utilizing gaseous mediators. Founded in 2009, the company listed on the TSX Venture Exchange in 2013 and was moved to the Toronto Stock Exchange in November 2020. In 2015, Antibe acquired Citagenix, a distributor involved in regenerative medicine.

Gaseous mediators are chemicals that are produced in small amounts by some cells of the mammalian body and have a number of biological signalling functions. There are three so-far-identified gaseous mediator molecules: nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO).

Prostaglandin inhibitors are drugs that inhibit the synthesis of prostaglandin in human body. There are various types of prostaglandins responsible for different physiological reactions such as maintaining the blood flow in stomach and kidney, regulating the contraction of involuntary muscles and blood vessels, and act as a mediator of inflammation and pain. Cyclooxygenase (COX) and Phospholipase A2 are the major enzymes involved in prostaglandin production, and they are the drug targets for prostaglandin inhibitors. There are mainly 2 classes of prostaglandin inhibitors, namely non- steroidal anti- inflammatory drugs (NSAIDs) and glucocorticoids. In the following sections, the medical uses, side effects, contraindications, toxicity and the pharmacology of these prostaglandin inhibitors will be discussed.

References

  1. "4-Carbamothioylphenyl 2-(6-methoxynaphthalen-2-yl)propanoate". PubChem. National Institute of Health. Retrieved February 9, 2021.
  2. "Otenaproxesul". IUPHAR/BPS Guide to Pharmacology. January 27, 2021.
  3. "Otenaproxesul (ATB-346)". Antibe Therapeutics. Retrieved February 17, 2021.
  4. "Otenaproxesul, (+/-)-". National Center for Advancing Translational Sciences. Retrieved February 9, 2021.
  5. Elsheikh W, Blackler RW, Flannigan KL, Wallace JL (September 15, 2014). "Enhanced chemopreventive effects of a hydrogen sulfide-releasing anti-inflammatory drug (ATB-346) in experimental colorectal cancer". Nitric Oxide. 41: 131–7. doi:10.1016/j.niox.2014.04.006. PMID   24747869 via PubMed.
  6. Gugliandolo E, Fusco R, D'Amico R, Militi A, Oteri G, Wallace JL, et al. (June 2018). "Anti-inflammatory effect of ATB-352, a H2S -releasing ketoprofen derivative, on lipopolysaccharide-induced periodontitis in rats". Pharmacological Research. 132: 220–231. doi:10.1016/j.phrs.2017.12.022. PMID   29287688. S2CID   12099369.
  7. Costa SK, Muscara MN, Allain T, Dallazen J, Gonzaga L, Buret AG, et al. (November 2020). "Enhanced Analgesic Effects and Gastrointestinal Safety of a Novel, Hydrogen Sulfide-Releasing Anti-Inflammatory Drug (ATB-352): A Role for Endogenous Cannabinoids". Antioxidants & Redox Signaling. 33 (14): 1003–1009. doi:10.1089/ars.2019.7884. PMC   7578177 . PMID   32064887.