Daunorubicin, also known as daunomycin, is a

chemotherapy medication Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) in a standard regimen. Chemotherapy may be given with a cura ...

used to treat

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

. Specifically it is used for

acute myeloid leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with haematopoiesis, normal blood cell production. Sympt ...

(AML),

acute lymphoblastic leukemia Acute lymphoblastic leukemia (ALL) is a cancer of the Lymphocyte, lymphoid line of blood cells characterized by the development of large numbers of lymphoblast, immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, ...

(ALL),

chronic myelogenous leukemia Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow and the accumula ...

(CML), and

Kaposi's sarcoma Kaposi's sarcoma (KS) is a type of cancer that can form masses on the skin, in lymph nodes, in the mouth, or in other organs. The skin lesions are usually painless, purple and may be flat or raised. Lesions can occur singly, multiply in a limite ...

. It is administered by

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

. A

liposomal A liposome is a small artificial vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, liposomes can be used as drug delivery ...

formulation known as

liposomal daunorubicin Liposomal daunorubicin (trade name DaunoXome) is a chemotherapy drug that is FDA approved to treat AIDS related Kaposi's sarcoma. It is also commonly used to treat specific types of leukaemia and non-Hodgkin lymphoma. Liposomal daunorubicin is intr ...

also exists. Common side effects include hair loss, vomiting,

bone marrow suppression Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting ( ...

, and inflammation of the inside of the mouth. Other severe side effects include

heart disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina pectoris, angina, myocardial infarction, heart attack), heart failure, ...

and tissue death at the site of injection. Use in

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

may harm the fetus. Daunorubicin is in the

anthracycline Anthracyclines are a class of drugs used in cancer chemotherapy that are extracted from '' Streptomyces peucetius'' bacterium. These compounds are used to treat many cancers, including leukemias, lymphomas, breast, stomach, uterine, ovarian, b ...

family of medication. It works in part by blocking the function of

topoisomerase II Type II topoisomerases are topoisomerases that cut both strands of the DNA helix simultaneously in order to manage DNA tangles and supercoils. They use the hydrolysis of Adenosine triphosphate, ATP, unlike Type I topoisomerase. In this process, t ...

. Daunorubicin was approved for medical use in the United States in 1979. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. It was originally isolated from bacteria of the ''

Streptomyces ''Streptomyces'', from στρεπτός (''streptós''), meaning "twisted", and μύκης (''múkés''), meaning "fungus", is the largest genus of Actinomycetota, and the type genus of the family Streptomycetaceae. Over 700 species of ''St ...

'' type.

Medical uses

It slows or stops the growth of cancer cells in the body. Treatment is usually performed together with other chemotherapy drugs (such as

cytarabine Cytarabine, also known as cytosine arabinoside (ara-C), is a chemotherapy medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma. It is given b ...

), and its administration depends on the type of tumor and the degree of response. In addition to its major use in treating acute myeloid leukemia, daunorubicin is also used to treat

neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the head, neck, chest, abdomen, or Vertebral column, spine. Symptoms may include ...

. Daunorubicin has been used with other chemotherapy agents to treat the blastic phase of

. Daunorubicin is also used as the starting material for semi-synthetic manufacturing of

doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toge ...

epirubicin Epirubicin is an anthracycline drug used for chemotherapy. It can be used in combination with other medications to treat breast cancer in patients who have had surgery to remove the tumor. It is marketed by Pfizer under the trade name Ellence in ...

and

idarubicin Idarubicin or 4-demethoxydaunorubicin is an anthracycline antileukemic drug. It inserts itself into DNA and prevents DNA unwinding by interfering with the enzyme topoisomerase II. It is an analog of daunorubicin, but the absence of a methoxy gro ...

Mechanism of action

Similar to

, daunorubicin interacts with DNA by intercalation and inhibition of macromolecular

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

. This inhibits the progression of the enzyme

, which relaxes supercoils in DNA; without action of topoisomerase II, these DNA supercoils interfere in

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, often th ...

of DNA. Daunorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process of replication. On binding to DNA, daunomycin intercalates, with its daunosamine residue directed toward the minor groove. It has the highest preference for two adjacent G/C

base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

s flanked on the 5' side by an A/T base pair. Crystallography shows that daunomycin induces a local unwinding angle of 8°, and other conformational disturbances of adjacent and second-neighbour base pairs. It can also induce

histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes ...

eviction from

chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...

upon intercalation.

History

In the 1950s, an

Italian Italian(s) may refer to: * Anything of, from, or related to the people of Italy over the centuries ** Italians, a Romance ethnic group related to or simply a citizen of the Italian Republic or Italian Kingdom ** Italian language, a Romance languag ...

research company,

Farmitalia Farmitalia was an Italian pharmaceutical company best known for its parallel discovery with Rhone-Poulenc of daunorubicin and subsequent discovery of doxorubicin. Farmitalia had been founded in 1935 as a joint venture by Rhone-Poulenc and Mon ...

Research Laboratories, began an organized effort to isolate anticancer compounds from soil-based

microbe A microorganism, or microbe, is an organism of microscopic size, which may exist in its single-celled form or as a colony of cells. The possible existence of unseen microbial life was suspected from antiquity, with an early attestation in ...

s. A soil sample was isolated from the area surrounding the Castel del Monte, a 13th-century castle in

Apulia Apulia ( ), also known by its Italian language, Italian name Puglia (), is a Regions of Italy, region of Italy, located in the Southern Italy, southern peninsular section of the country, bordering the Adriatic Sea to the east, the Strait of Ot ...

. A new strain of ''

Streptomyces peucetius ''Streptomyces peucetius'' is a bacterium species in the genus ''Streptomyces''. ''S. peucetius'' produces the anthracycline antitumor antibiotics daunorubicin and doxorubicin Doxorubicin, sold under the brand name Adriamycin among others ...

'' which produced a red pigment was isolated, and an antibiotic was produced from this bacterium that was found to have good activity against

murine The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. Members of this subfamily are called murines. In terms of species richness, this subfamily is larger than all mammal families excep ...

tumors. Since a group of

French French may refer to: * Something of, from, or related to France ** French language, which originated in France ** French people, a nation and ethnic group ** French cuisine, cooking traditions and practices Arts and media * The French (band), ...

researchers discovered the same compound at about the same time, the two teams named the compound daunorubicin, combining the name ''

Dauni The Daunians () were an Iapygian tribe that inhabited northern Apulia in classical antiquity. Two other Iapygian tribes, the Peucetians and the Messapians, inhabited the central and southern Apulia respectively. Although all three tribes spoke t ...

'', a pre-Roman tribe that occupied the area of Italy where the compound was isolated, with the French word for

ruby Ruby is a pinkish-red-to-blood-red-colored gemstone, a variety of the mineral corundum ( aluminium oxide). Ruby is one of the most popular traditional jewelry gems and is very durable. Other varieties of gem-quality corundum are called sapph ...

, ''rubis'', describing the color. Clinical trials began in the 1960s, and the drug saw success in treating acute leukemia and lymphoma. However, by 1967, it was recognized that daunorubicin could produce fatal cardiac toxicity. In 2015–16, a team at

Ohio State University The Ohio State University (Ohio State or OSU) is a public university, public Land-grant university, land-grant research university in Columbus, Ohio, United States. A member of the University System of Ohio, it was founded in 1870. It is one ...

"showed that, by carefully manipulating strands of viral DNA, an origami structure with complex folds can be created in just 10 minutes. Incredibly, these structures are only 100 nanometers across – that’s 1,000 times smaller than the width of a human hair. Small volumes of daunorubicin can be wrapped up in these minuscule pods, which can then be released into a leukemia cell-filled environment."

Route of administration

Daunorubicin should only be administered in a rapid

intravenous infusion Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

. It should not be administered

intramuscular Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles hav ...

ly or subcutaneously, since it may cause extensive tissue

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who i ...

. It should also never be administered

intrathecal Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space (sin. ''intrathecal space'') so that it reaches the cerebrospinal fluid (CSF). It is useful in several applic ...

ly (into the

spinal canal In human anatomy, the spinal canal, vertebral canal or spinal cavity is an elongated body cavity enclosed within the dorsal bony arches of the vertebral column, which contains the spinal cord, spinal roots and dorsal root ganglia. It is a pro ...

), as this will cause extensive damage to the

nervous system In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. Th ...

and may lead to

death Death is the end of life; the irreversible cessation of all biological functions that sustain a living organism. Death eventually and inevitably occurs in all organisms. The remains of a former organism normally begin to decompose sh ...

. Daunorubicin has been used intravitreally (inside the eye) for the purposes of preventing proliferative vitreoretinopathy, a common complication following retinal detachment surgery, but has not been found to be effective and is not used for any other ophthalmic purposes at this time.

References

{{Authority control Anthracyclines Anthraquinone glycosides Topoisomerase inhibitors IARC Group 2B carcinogens World Health Organization essential medicines Wikipedia medicine articles ready to translate DNA intercalaters Italian inventions French inventions