Ex-Rad (or Ex-RAD; recilisib sodium (
INN
Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...
,
USAN
280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk（于山國）was Ulleungdo（鬱陵島）
Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms period. According to the ...
); development code ON 01210.Na) is an experimental drug being
developed by Onconova Therapeutics and the
U.S. Department of Defense
The United States Department of Defense (DoD, USDOD or DOD) is an executive branch department of the federal government charged with coordinating and supervising all agencies and functions of the government directly related to national secu ...
.
It is being studied as a radiation protection agent. Chemically, it is the sodium salt of 4-carboxystyryl-4-chlorobenzylsulfone.
Clinical trials
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".
A study in mice demonstrated the efficacy of Ex-Rad by increasing the survival rate of mice exposed to typically lethal whole-body
irradiation
Irradiation is the process by which an object is exposed to radiation. The exposure can originate from various sources, including natural sources. Most frequently the term refers to ionizing radiation, and to a level of radiation that will serv ...
. The study tested oral and
parenteral
A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body.
Routes of administration are generally classified by the location at which the substance is applied. ...
administration of Ex-Rad for both pre- and post-exposure radiomitigation.
Research on Ex-Rad has involved collaboration with the
Armed Forces Radiobiology Research Institute
The Armed Forces Radiobiology Research Institute (AFRRI) is an American triservice research laboratory in Bethesda, Maryland chartered by Congress in 1960 and formally established in 1961. It conducts research in the field of radiobiology and r ...
(AFRRI), the Department of Biochemistry and Molecular & Cellular Biology at
Georgetown University
Georgetown University is a private university, private research university in the Georgetown (Washington, D.C.), Georgetown neighborhood of Washington, D.C. Founded by Bishop John Carroll (archbishop of Baltimore), John Carroll in 1789 as Georg ...
,
Long Island University
Long Island University (LIU) is a private university with two main campuses, LIU Post and LIU Brooklyn, in the U.S. state of New York. It offers more than 500 academic programs at its main campuses, online, and at multiple non-residential. LI ...
's Arnold & Marie Schwartz College of Pharmacy, and the Department of Oncological Sciences at the
Mt. Sinai School of Medicine.
Mechanism of action
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
In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired valence electron.
With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spon ...
or arresting the
cell cycle
The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA ( DNA replication) and some of its organelles, and sub ...
. Instead, they claim it employs a "novel mechanism" involving "intracellular signaling, damage sensing, and DNA repair pathways".
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
Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells ...
and
gastrointestinal
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
tissues from radiation injury when given either before or after exposure.
See also
*
CBLB502
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 a ...
(Entolimod), a compound being studied for its ability to suppresses
apoptotic
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes inc ...
cell death in
hematopoietic
Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells ...
and
gastrointestinal
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
cells.
*
Amifostine
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.
Indications
Amifostine is used therapeut ...
(WR2721), the first selective-target and broad-spectrum radioprotector, upregulates
DNA repair
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
*
Filgrastim
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 ...
(Neupogen), a hematopoietic countermeasure of
acute radiation syndrome (ARS)
*
Pegfilgrastim
Pegfilgrastim, sold under the brand name Neulasta among others, is a PEGylated form of the recombinant human granulocyte colony-stimulating factor (GCSF) analog filgrastim. It serves to stimulate the production of white blood cells (neutrophils) ...
(Neulasta), longer acting than its parent, filgrastim
*
Sargramostim
Sargramostim (tradename Leukine) is a recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) that functions as an immunostimulator.
Medical uses
Sargramostim is primarily used for myeloid reconstitution after autologous or alloge ...
(leukine), similar in use to filgrastim
*
''N''-Acetylcysteine, protects against DNA damage, suggested to be comparable to amifostine
*
Thrombomodulin
Thrombomodulin (TM), CD141 or BDCA-3 is an integral membrane protein expressed on the surface of endothelial cells and serves as a cofactor for thrombin. It reduces blood coagulation by converting thrombin to an anticoagulant enzyme from a procoa ...
*
Activated protein C
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIX, is a zymogen, that is, an inactive enzyme. The activated form plays an important role in regulating anticoagulation, inflammation, and apoptosis, cell death and ...
*
Chelation therapy
Chelation therapy is a medical procedure that involves the administration of chelating agents to remove heavy metals from the body. Chelation therapy has a long history of use in clinical toxicology and remains in use for some very specific medi ...
, a countermeasure for treating internal
radio-isotope
A radionuclide (radioactive nuclide, radioisotope or radioactive isotope) is a nuclide that has excess nuclear energy, making it unstable. This excess energy can be used in one of three ways: emitted from the nucleus as gamma radiation; transferr ...
contamination
*
DPTA
Pentetic acid or diethylenetriaminepentaacetic acid (DTPA) is an aminopolycarboxylic acid consisting of a diethylenetriamine backbone with five carboxymethyl groups. The molecule can be viewed as an expanded version of EDTA and is used similarly ...
, a chelation agent used to eliminate
actinide
The actinide () or actinoid () series encompasses the 15 metallic chemical elements with atomic numbers from 89 to 103, actinium through lawrencium. The actinide series derives its name from the first element in the series, actinium. The inf ...
s that have been ingested, one of three U.S.
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) radioprotectants stockpiled
*
Prussian blue
Prussian blue (also known as Berlin blue, Brandenburg blue or, in painting, Parisian or Paris blue) is a dark blue pigment produced by oxidation of ferrous ferrocyanide salts. It has the chemical formula Fe Cyanide.html" ;"title="e(Cyanide">CN ...
/
radiogardase, a chelation agent to treat radio-
Cesium
Caesium ( IUPAC spelling) (or cesium in American English) is a chemical element with the symbol Cs and atomic number 55. It is a soft, silvery-golden alkali metal with a melting point of , which makes it one of only five elemental metals that ...
and
thallium
Thallium is a chemical element with the symbol Tl and atomic number 81. It is a gray post-transition metal that is not found free in nature. When isolated, thallium resembles tin, but discolors when exposed to air. Chemists William Crookes a ...
consumption, one of three the FDA radioprotectants stockpiled
*
Potassium iodide
Potassium iodide is a chemical compound, medication, and dietary supplement. It is a medication used for treating hyperthyroidism, in radiation emergencies, and for protecting the thyroid gland when certain types of radiopharmaceuticals are us ...
, a
prophylactic
Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
drug recommended before entering
radioiodine
There are 37 known isotopes of iodine (53I) from 108I to 144I; all undergo radioactive decay except 127I, which is stable. Iodine is thus a monoisotopic element.
Its longest-lived radioactive isotope, 129I, has a half-life of 15.7 million year ...
environments, one of three FDA radioprotectants stockpiled
*
Kojic acid
Kojic acid is a chelation agent produced by several species of fungi, especially ''Aspergillus oryzae'', which has the Japanese common name ''koji''. Kojic acid is a by-product in the fermentation process of malting rice, for use in the manufactur ...
*
Hyaluronan
Hyaluronic acid (; abbreviated HA; conjugate base hyaluronate), also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminogl ...
*
Petkau effect
References
{{Reflist
Radiation health effects
Radiobiology
Drugs with unknown mechanisms of action
Experimental drugs
Chloroarenes
Sulfones
Benzoates