amrubicinol profile

amrubicinol: a diastereoisomeric mixture; a synthetic antracycline drug [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

amrubicinol : A diastereoisomeric mixture resulting from the formal reduction of the acetyl group at position 9 of amrubicin to the corresponding 1-hydroxyethyl group. The active metabolite of amrubicin in lung cancer patients. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

ID Source	ID
PubMed CID	11755113
CHEBI ID	156204
MeSH ID	M0298782

Synonym
(7s,9s)-9-amino-7-{[(2s,4s,5r)-4,5-dihydroxytetrahydro-2h-pyran-2-yl]oxy}-6,11-dihydroxy-9-(1-hydroxyethyl)-7,8,9,10-tetrahydrotetracene-5,12-dione
amrubicinol
CHEBI:156204
(7s,9s)-9-amino-7-[(2s,4s,5r)-4,5-dihydroxyoxan-2-yl]oxy-6,11-dihydroxy-9-(1-hydroxyethyl)-8,10-dihydro-7h-tetracene-5,12-dione

Research Excerpts

Overview

Ammubicinol (AMR-OH) is an active metabolite of amrubicin. It is a synthetic 9-aminoanthracycline derivative.

Excerpt	Reference	Relevance
"Amrubicinol (AMR-OH) is an active metabolite of amrubicin (AMR), a novel synthetic 9-aminoanthracycline derivative. "	( Plasma concentration of amrubicinol in plateau phase in patients treated for 3 days with amrubicin is correlated with hematological toxicities. Asai, K; Hirata, K; Kimura, T; Kudoh, S; Kyoh, S; Mitsuoka, S; Tanaka, H; Tochino, Y; Umekawa, K; Yoshimura, N, 2009)	2.1

Effects

Excerpt	Reference	Relevance
"Amrubicinol has a higher activity level inside the cells than does amrubicin."	( Cytotoxicity of amrubicin, a novel 9-aminoanthracycline, and its active metabolite amrubicinol on human tumor cells. Hanada, M; Ichii, S; Morisada, S; Noguchi, T; Yamaoka, T; Yanagi, Y, 1998)	1.25

Toxicity

Excerpt	Reference	Relevance
" We have characterized how amrubicin converted to ROS or secondary alcohol metabolite in comparison with doxorubicin (that formed both toxic species) or epirubicin (that lacked ROS formation and showed an impaired conversion to alcohol metabolite)."	( Pharmacokinetic characterization of amrubicin cardiac safety in an ex vivo human myocardial strip model. II. Amrubicin shows metabolic advantages over doxorubicin and epirubicin. Aukerman, SL; Chello, M; Covino, E; Gonzalez Paz, O; Menna, P; Minotti, G; Salvatorelli, E; Sung, V; Surapaneni, S, 2012)	0.38

Pharmacokinetics

The pharmacokinetic (PK)-pharmacodynamic (PD) relationship of amrubicin and its active metabolite, amRubicinol, has only been evaluated using trough levels of these agents since the full PK profiles not yet been clarified so far. The subsequent PK-PD analyses indicate that the clearance of am Rubinol is the major determinant of neutropenia.

Excerpt	Reference	Relevance
" The method was successfully applied to a clinical pharmacokinetic study of amrubicin and amrubicinol in cancer patients."	( Simple and sensitive HPLC method for determination of amrubicin and amrubicinol in human plasma: application to a clinical pharmacokinetic study. Ando, R; Kimura, T; Makino, Y; Nishigaki, R; Tamura, T; Yamamoto, H; Yamamoto, N; Yokote, N, 2010)	0.82
" The pharmacokinetic parameters of amrubicin have not yet been investigated in hemodialysis patients, although it had been expected that amrubicin might not be cleared by hemodialysis because of its high lipid solubility, high protein binding rate and low urinary excretion rate."	( [Pharmacokinetic study of amrubicin in a case of small lung cancer on hemodialysis]. Chihara, S; Demizu, M; Hosoi, K; Igarashi, T; Min, K; Nakashima, Y; Ohsawa, M; Tomiyama, N; Ueda, H, 2009)	0.35
"The pharmacokinetic (PK)-pharmacodynamic (PD) relationship of amrubicin and its active metabolite, amrubicinol, has only been evaluated using trough levels of these agents since the full PK profiles not yet been clarified so far."	( Pharmacokinetic and pharmacodynamic study on amrubicin and amrubicinol in Japanese patients with lung cancer. Ando, R; Asahina, H; Goto, Y; Kunitoh, H; Makino, Y; Nokihara, H; Ohe, Y; Sato, H; Sekine, I; Sugiyama, E; Tamura, T; Tanai, C; Yamamoto, H; Yamamoto, N; Yokote, N, 2012)	0.84
"The pharmacokinetic profiles of amrubicin and amrubicinol were clarified, and the subsequent PK-PD analyses indicate that the clearance of amrubicinol is the major determinant of neutropenia."	( Pharmacokinetic and pharmacodynamic study on amrubicin and amrubicinol in Japanese patients with lung cancer. Ando, R; Asahina, H; Goto, Y; Kunitoh, H; Makino, Y; Nokihara, H; Ohe, Y; Sato, H; Sekine, I; Sugiyama, E; Tamura, T; Tanai, C; Yamamoto, H; Yamamoto, N; Yokote, N, 2012)	0.88
"Limited sampling points for both amrubicin (AMR) and its active metabolite amrubicinol (AMR-OH) were simultaneously optimized using Akaike's information criterion (AIC) calculated by pharmacokinetic modeling."	( Simultaneous optimization of limited sampling points for pharmacokinetic analysis of amrubicin and amrubicinol in cancer patients. Hayashi, Y; Makihara, RA; Makino, Y; Nokihara, H; Ohe, Y; Sato, H; Sugiyama, E; Watanabe, M; Yamamoto, N, 2016)	0.88
"In this pharmacokinetic study, 40 mg/m(2) of AMR was administered as a 5-min infusion on three consecutive days to 21 Japanese lung cancer patients."	( Simultaneous optimization of limited sampling points for pharmacokinetic analysis of amrubicin and amrubicinol in cancer patients. Hayashi, Y; Makihara, RA; Makino, Y; Nokihara, H; Ohe, Y; Sato, H; Sugiyama, E; Watanabe, M; Yamamoto, N, 2016)	0.65
"25, 2, 4 and 8 h, enabling less frequent blood sampling in further expanded pharmacokinetic studies for both AMR and AMR-OH."	( Simultaneous optimization of limited sampling points for pharmacokinetic analysis of amrubicin and amrubicinol in cancer patients. Hayashi, Y; Makihara, RA; Makino, Y; Nokihara, H; Ohe, Y; Sato, H; Sugiyama, E; Watanabe, M; Yamamoto, N, 2016)	0.65

Compound-Compound Interactions

Excerpt	Reference	Relevance
"A combination phase I study was conducted in a cohort of lung cancer patients to determine the maximum tolerated dose (MTD) and toxicities of irinotecan (CPT-11), a topoisomerase I inhibitor, in combination with amrubicin (AMR), a topoisomerase II inhibitor, and to observe their antitumor activities."	( A phase I study of irinotecan in combination with amrubicin for advanced lung cancer patients. Fukuoka, M; Kaneda, H; Kurata, T; Nakagawa, K; Tamura, K; Uejima, H, )	0.13

Dosage Studied

Excerpt	Relevance	Reference
" There is a possibility that monitoring of the plasma concentrations of amrubicin and amrubicinol may provide an efficient tool for establishing the optimal dosage of amrubicin in each patient."	( Pharmacokinetics of amrubicin and its active metabolite amrubicinol in lung cancer patients. Hamada, A; Hira, A; Kishi, H; Matsumoto, M; Matsunaga, Y; Moriyama, E; Okamoto, I; Saito, H; Sasaki, J; Watanabe, H, 2006)	0.8

[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Role	Description
topoisomerase II inhibitor	null
antineoplastic agent	A substance that inhibits or prevents the proliferation of neoplasms.
apoptosis inducer	Any substance that induces the process of apoptosis (programmed cell death) in multi-celled organisms.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Class	Description
diastereoisomeric mixture	A mixture composed of two or more diastereoisomers (stereoisomers not related as mirror images).
tetracenes	Compounds containing a tetracene skeleton.
secondary alcohol	A secondary alcohol is a compound in which a hydroxy group, -OH, is attached to a saturated carbon atom which has two other carbon atoms attached to it.
quinone	Compounds having a fully conjugated cyclic dione structure, such as that of benzoquinones, derived from aromatic compounds by conversion of an even number of -CH= groups into -C(=O)- groups with any necessary rearrangement of double bonds (polycyclic and heterocyclic analogues are included).
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	4 (16.00)	18.2507
2000's	11 (44.00)	29.6817
2010's	10 (40.00)	24.3611
2020's	0 (0.00)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	5 (19.23%)	5.53%
Reviews	0 (0.00%)	6.00%
Case Studies	1 (3.85%)	4.05%
Observational	0 (0.00%)	0.25%
Other	20 (76.92%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Trials	Classes	Roles
uracil 2,4-dihydroxypyrimidine: a urinary biomarker for bipolar disorder	2.03	1	0	pyrimidine nucleobase; pyrimidone	allergen; Daphnia magna metabolite; Escherichia coli metabolite; human metabolite; mouse metabolite; prodrug; Saccharomyces cerevisiae metabolite
verapamil Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent.. verapamil : A racemate comprising equimolar amounts of dexverapamil and (S)-verapamil. An L-type calcium channel blocker of the phenylalkylamine class, it is used (particularly as the hydrochloride salt) in the treatment of hypertension, angina pectoris and cardiac arrhythmia, and as a preventive medication for migraine.. 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile : A tertiary amino compound that is 3,4-dimethoxyphenylethylamine in which the hydrogens attached to the nitrogen are replaced by a methyl group and a 4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl group.	2.06	1	0	aromatic ether; nitrile; polyether; tertiary amino compound
disopyramide Disopyramide: A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties.. disopyramide : A monocarboxylic acid amide that is butanamide substituted by a diisopropylamino group at position 4, a phenyl group at position 2 and a pyridin-2-yl group at position 2. It is used as a anti-arrhythmia drug.	3.41	1	1	monocarboxylic acid amide; pyridines; tertiary amino compound	anti-arrhythmia drug
tegafur [no description available]	2.03	1	0	organohalogen compound; pyrimidines
quinazolines Quinazolines: A group of aromatic heterocyclic compounds that contain a bicyclic structure with two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring.. quinazoline : A mancude organic heterobicyclic parent that is naphthalene in which the carbon atoms at positions 1 and 3 have been replaced by nitrogen atoms.. quinazolines : Any organic heterobicyclic compound based on a quinazoline skeleton and its substituted derivatives.	2.03	1	0	azaarene; mancude organic heterobicyclic parent; ortho-fused heteroarene; quinazolines
deoxycytidine [no description available]	2.03	1	0	pyrimidine 2'-deoxyribonucleoside	Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite
camptothecin NSC 100880: carboxylate (opened lactone) form of camptothecin; RN refers to (S)-isomer; structure given in first source	2.75	3	0	delta-lactone; pyranoindolizinoquinoline; quinoline alkaloid; tertiary alcohol	antineoplastic agent; EC 5.99.1.2 (DNA topoisomerase) inhibitor; genotoxin; plant metabolite
daunorubicin Daunorubicin: A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.. anthracycline : Anthracyclines are polyketides that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine.. daunorubicin : A natural product found in Actinomadura roseola.	2.03	1	0	aminoglycoside antibiotic; anthracycline; p-quinones; tetracenequinones	antineoplastic agent; bacterial metabolite
paclitaxel Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).	2.08	1	0	taxane diterpenoid; tetracyclic diterpenoid	antineoplastic agent; human metabolite; metabolite; microtubule-stabilising agent
etoposide [no description available]	2.73	3	0	beta-D-glucoside; furonaphthodioxole; organic heterotetracyclic compound	antineoplastic agent; DNA synthesis inhibitor
epirubicin Epirubicin: An anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA.	2.07	1	0	aminoglycoside; anthracycline antibiotic; anthracycline; deoxy hexoside; monosaccharide derivative; p-quinones; primary alpha-hydroxy ketone; tertiary alpha-hydroxy ketone	antimicrobial agent; antineoplastic agent; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor
gemcitabine gemcitabine : A 2'-deoxycytidine having geminal fluoro substituents in the 2'-position. An inhibitor of ribonucleotide reductase, gemcitabine is used in the treatment of various carcinomas, particularly non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer.	2.03	1	0	organofluorine compound; pyrimidine 2'-deoxyribonucleoside	antimetabolite; antineoplastic agent; antiviral drug; DNA synthesis inhibitor; EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor; environmental contaminant; immunosuppressive agent; photosensitizing agent; prodrug; radiosensitizing agent; xenobiotic
irinotecan [no description available]	7.75	3	0	carbamate ester; delta-lactone; N-acylpiperidine; pyranoindolizinoquinoline; ring assembly; tertiary alcohol; tertiary amino compound	antineoplastic agent; apoptosis inducer; EC 5.99.1.2 (DNA topoisomerase) inhibitor; prodrug
gefitinib [no description available]	2.03	1	0	aromatic ether; monochlorobenzenes; monofluorobenzenes; morpholines; quinazolines; secondary amino compound; tertiary amino compound	antineoplastic agent; epidermal growth factor receptor antagonist
amrubicin amrubicin: structure in first source; a 9-amino-anthracycline antibiotic. amrubicin : A synthetic anthracycline antibiotic with molecular formula C25H25NO9. A specific inhibitor of topoisomerase II, it is used (particularly as the hydrochloride salt) in the treatment of cancer, especially lung cancer, where it is a prodrug for the active metabolite, ambrucinol.	7.08	23	4	anthracycline antibiotic; methyl ketone; primary amino compound; quinone; tetracenes	antineoplastic agent; prodrug; topoisomerase II inhibitor
interleukin-8 Interleukin-8: A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells.	2.03	1	0

Condition	Relationship Strength	Studies	Trials
Cancer of Lung [description not available]	6.13	16	2
Lung Neoplasms Tumors or cancer of the LUNG.	6.13	16	2
Carcinoma, Oat Cell [description not available]	5.43	5	3
Carcinoma, Non-Small Cell Lung [description not available]	5.6	6	3
Blood Diseases [description not available]	3.43	1	1
Leukocytopenia [description not available]	5.03	3	3
Carcinoma, Non-Small-Cell Lung A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.	5.6	6	3
Hematologic Diseases Disorders of the blood and blood forming tissues.	3.43	1	1
Leukopenia A decrease in the number of LEUKOCYTES in a blood sample below the normal range (LEUKOCYTE COUNT less than 4000).	5.03	3	3
Neutropenia A decrease in the number of NEUTROPHILS found in the blood.	4.39	2	2
Carcinoma, Small Cell An anaplastic, highly malignant, and usually bronchogenic carcinoma composed of small ovoid cells with scanty neoplasm. It is characterized by a dominant, deeply basophilic nucleus, and absent or indistinct nucleoli. (From Stedman, 25th ed; Holland et al., Cancer Medicine, 3d ed, p1286-7)	5.43	5	3
Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)	2.05	1	0
Carcinoma, Small Cell Lung [description not available]	2.98	4	0
Small Cell Lung Carcinoma A form of highly malignant lung cancer that is composed of small ovoid cells (SMALL CELL CARCINOMA).	2.98	4	0
Adenocarcinoma, Basal Cell [description not available]	2.95	4	0
Carcinoma, Epidermoid [description not available]	2.06	1	0
Adenocarcinoma A malignant epithelial tumor with a glandular organization.	2.95	4	0
Carcinoma, Squamous Cell A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)	2.06	1	0
Carcinoma, Large Cell A tumor of undifferentiated (anaplastic) cells of large size. It is usually bronchogenic. (From Dorland, 27th ed)	2.06	1	0
Benign Neoplasms [description not available]	3.47	1	1
Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	3.47	1	1
Anoxemia [description not available]	3.41	1	1
Auricular Fibrillation [description not available]	3.41	1	1
Breathlessness [description not available]	3.41	1	1
Experimental Lung Inflammation Inflammation of any part, segment or lobe, of the lung parenchyma.	3.41	1	1
Thrombopenia [description not available]	4.38	2	2
Local Neoplasm Recurrence [description not available]	3.41	1	1
Hypoxia Sub-optimal OXYGEN levels in the ambient air of living organisms.	3.41	1	1
Atrial Fibrillation Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.	3.41	1	1
Dyspnea Difficult or labored breathing.	3.41	1	1
Pneumonia Infection of the lung often accompanied by inflammation.	3.41	1	1
Thrombocytopenia A subnormal level of BLOOD PLATELETS.	4.38	2	2
Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply.	2.43	2	0
Cancer of Stomach [description not available]	2.42	2	0
Stomach Neoplasms Tumors or cancer of the STOMACH.	2.42	2	0
Hematologic Malignancies [description not available]	1.99	1	0
Bladder Cancer [description not available]	1.99	1	0
Cancer of Colon [description not available]	1.99	1	0
Cancer of Kidney [description not available]	1.99	1	0
Osteogenic Sarcoma [description not available]	1.99	1	0
Urinary Bladder Neoplasms Tumors or cancer of the URINARY BLADDER.	1.99	1	0
Colonic Neoplasms Tumors or cancer of the COLON.	1.99	1	0
Kidney Neoplasms Tumors or cancers of the KIDNEY.	1.99	1	0
Osteosarcoma A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed)	1.99	1	0
Hematologic Neoplasms Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.	1.99	1	0
Leukemia P388 An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.	2	1	0

amrubicinol

Description

Cross-References

Synonyms (4)

Research Excerpts

Overview

Effects

Toxicity

Pharmacokinetics

Compound-Compound Interactions

Dosage Studied

Roles (3)

Drug Classes (4)

Research

Studies (25)

Market Indicators

Research Demand Index: 11.29

Study Types

amrubicinol

Description

Cross-References

Synonyms (4)

Research Excerpts

Overview

Effects

Toxicity

Pharmacokinetics

Compound-Compound Interactions

Dosage Studied

Roles (3)

Drug Classes (4)

Research

Studies (25)

Market Indicators

Research Demand Index: 11.29

Study Types

Related Drugs (16)

Related Conditions (46)