Names | |
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Preferred IUPAC name Sodium 4-{(1E)-2-[(4-chlorophenyl)methanesulfonyl]ethen-1-yl}benzoate | |
Identifiers | |
3D model (JSmol) | |
KEGG | |
PubChem CID | |
UNII | |
CompTox Dashboard (EPA) | |
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Properties | |
C16H12ClNaO4S | |
Molar mass | 358.77 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Ex-Rad (or Ex-RAD; recilisib sodium (INN, USAN); development code ON 01210.Na) is an experimental drug being developed by Onconova Therapeutics and the U.S. Department of Defense. [1] It is being studied as a radiation protection agent. [2] Chemically, it is the sodium salt of 4-carboxystyryl-4-chlorobenzylsulfone. [3]
The results of two Phase I clinical studies in healthy human volunteers indicate that subcutaneously injected Ex-Rad is safe and well tolerated, with "no evidence of systemic side effects". [4] A study in mice demonstrated the efficacy of Ex-Rad by increasing the survival rate of mice exposed to typically lethal whole-body irradiation. The study tested oral and parenteral administration of Ex-Rad for both pre- and post-exposure radiomitigation. [1]
Research on Ex-Rad has involved collaboration with the Armed Forces Radiobiology Research Institute (AFRRI), the Department of Biochemistry and Molecular & Cellular Biology at Georgetown University, Long Island University's Arnold & Marie Schwartz College of Pharmacy, and the Department of Oncological Sciences at the Mt. Sinai School of Medicine. [1]
Onconova reports that Ex-Rad protects cells exposed to radiation against DNA damage, and that the drug's mechanism of action does not involve scavenging free radicals or arresting the cell cycle. Instead, they claim it employs a "novel mechanism" involving "intracellular signaling, damage sensing, and DNA repair pathways". [4] Ex-RAD is a chlorobenzylsulfone derivative that works after free radicals have damaged DNA. Onconova CEO Ramesh Kumar believes this is a better approach than trying to scavenge free radicals. “Free radicals are very short-lived, and so the window of opportunity to give a drug is very narrow,” he says. In cell and animal models, Ex-RAD protects hematopoietic and gastrointestinal tissues from radiation injury when given either before or after exposure. [5]
Acute radiation syndrome (ARS), also known as radiation sickness or radiation poisoning, is a collection of health effects that are caused by being exposed to high amounts of ionizing radiation in a short period of time. Symptoms can start within an hour of exposure, and can last for several months. Early symptoms are usually nausea, vomiting and loss of appetite. In the following hours or weeks, initial symptoms may appear to improve, before the development of additional symptoms, after which either recovery or death follow.
A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include fatigue, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia.
N-acetylcysteine, also known as Acetylcysteine and NAC, is a medication that is used to treat paracetamol (acetaminophen) overdose and to loosen thick mucus in individuals with chronic bronchopulmonary disorders such as pneumonia and bronchitis. It has been used to treat lactobezoar in infants. It can be taken intravenously, orally, or inhaled as a mist. It is also sometimes used as a dietary supplement.
Granulocyte colony-stimulating factor, also known as colony-stimulating factor 3, is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.
Filgrastim, sold under the brand name Neupogen among others, is a medication used to treat low neutrophil count. Low neutrophil counts may occur with HIV/AIDS, following chemotherapy or radiation poisoning, or be of an unknown cause. It may also be used to increase white blood cells for gathering during leukapheresis. It is given either by injection into a vein or under the skin. Filgrastim is a leukocyte growth factor.
Pyridoxamine is one form of vitamin B6. Chemically it is based on a pyridine ring structure, with hydroxyl, methyl, aminomethyl, and hydroxymethyl substituents. It differs from pyridoxine by the substituent at the 4-position. The hydroxyl at position 3 and aminomethyl group at position 4 of its ring endow pyridoxamine with a variety of chemical properties, including the scavenging of free radical species and carbonyl species formed in sugar and lipid degradation and chelation of metal ions that catalyze Amadori reactions.
The free radical theory of aging states that organisms age because cells accumulate free radical damage over time. A free radical is any atom or molecule that has a single unpaired electron in an outer shell. While a few free radicals such as melanin are not chemically reactive, most biologically relevant free radicals are highly reactive. For most biological structures, free radical damage is closely associated with oxidative damage. Antioxidants are reducing agents, and limit oxidative damage to biological structures by passivating them from free radicals.
In chemistry and biology, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (O2), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (O2H), superoxide (O2-), hydroxyl radical (OH.), and singlet oxygen. ROS are pervasive because they are readily produced from O2, which is abundant. ROS are important in many ways, both beneficial and otherwise. ROS function as signals, that turn on and off biological functions. They are intermediates in the redox behavior of O2, which is central to fuel cells. ROS are central to the photodegradation of organic pollutants in the atmosphere. Most often however, ROS are discussed in a biological context, ranging from their effects on aging and their role in causing dangerous genetic mutations.
Carboplatin, sold under the brand name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is used by injection into a vein.
Cisplatin is a chemical compound with formula cis-[Pt(NH3)2Cl2]. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, brain tumors and neuroblastoma. It is given by injection into a vein.
Sunless tanning, also known as UV filled tanning, self tanning, spray tanning, or fake tanning, refers to the effect of a suntan without exposure to the Sun. Sunless tanning involves the use of oral agents (carotenids), or creams, lotions or sprays applied to the skin. Skin-applied products may be skin-reactive agents or temporary bronzers (colorants).
Amifostine (ethiofos) is a cytoprotective adjuvant used in cancer chemotherapy and radiotherapy involving DNA-binding chemotherapeutic agents. It is marketed by Clinigen Group under the trade name Ethyol.
Azacitidine, sold under the brand name Vidaza among others, is a medication used for the treatment of myelodysplastic syndrome, myeloid leukemia, and juvenile myelomonocytic leukemia. It is a chemical analog of cytidine, a nucleoside in DNA and RNA. Azacitidine and its deoxy derivative, decitabine were first synthesized in Czechoslovakia as potential chemotherapeutic agents for cancer.
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism causes base damage, as well as strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., O−
2, OH and H2O2. Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling.
Streptozotocin or streptozocin (STZ) is a naturally occurring alkylating antineoplastic agent that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. It is used in medicine for treating certain cancers of the islets of Langerhans and used in medical research to produce an animal model for hyperglycemia and Alzheimer's in a large dose, as well as type 2 diabetes or type 1 diabetes with multiple low doses.
Topotecan, sold under the brand name Hycamtin among others, is a chemotherapeutic agent medication that is a topoisomerase inhibitor. It is a synthetic, water-soluble analog of the natural chemical compound camptothecin. It is used in the form of its hydrochloride salt to treat ovarian cancer, lung cancer and other cancer types.
Dexrazoxane hydrochloride, sold under the brand name Zinecard among others, is a cardioprotective agent. It was discovered in 1972. The IV administration of dexrazoxane is in acidic condition with HCl adjusting the pH.
Entolimod (CBLB502) is being developed by Cleveland Biolabs, Inc. for dual indications under the U.S. Food & Drug Administration’s (FDA) animal efficacy rule as a pivotal-stage radiation countermeasure, and under the FDA’s traditional drug approval pathway as a cancer treatment.
Temozolomide, sold under the brand name Temodar among others, is an anticancer medication used to treat brain tumors such as glioblastoma and anaplastic astrocytoma. It is taken by mouth or via intravenous infusion.
Treatment of the inherited blood disorder thalassemia depends upon the level of severity. For mild forms of the condition, advice and counseling are often all that are necessary. For more severe forms, treatment may consist in blood transfusion; chelation therapy to reverse iron overload, using drugs such as deferoxamine, deferiprone, or deferasirox; medication with the antioxidant indicaxanthin to prevent the breakdown of hemoglobin; or a bone marrow transplant using material from a compatible donor, or from the patient's mother. Removal of the spleen (splenectomy) could theoretically help to reduce the need for blood transfusions in people with thalassaemia major or intermedia but there is currently no reliable evidence from clinical trials about its effects. Population screening has had some success as a preventive measure.