IDARUBICIN HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H27NO9.ClH
Molecular Weight	533.955
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.[H][C@@]1(C[C@H](N)[C@H](O)[C@H](C)O1)O[C@H]2C[C@@](O)(CC3=C(O)C4=C(C(=O)C5=C(C=CC=C5)C4=O)C(O)=C23)C(C)=O

InChI

InChIKey=JVHPTYWUBOQMBP-RVFAQHLVSA-N

InChI=1S/C26H27NO9.ClH/c1-10-21(29)15(27)7-17(35-10)36-16-9-26(34,11(2)28)8-14-18(16)25(33)20-19(24(14)32)22(30)12-5-3-4-6-13(12)23(20)31;/h3-6,10,15-17,21,29,32-34H,7-9,27H2,1-2H3;1H/t10-,15-,16-,17-,21+,26-;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0a5a6d93-cc1e-4d7f-8da1-446c134503b3&type=display | https://www.drugbank.ca/drugs/DB01177

Idarubicin is an antineoplastic in the anthracycline class.Idarubicin hydrochloride is a DNA-intercalating analog of daunorubicin which has an inhibitory effect on nucleic acid synthesis and interacts with the enzyme topoisomerase II. The absence of a methoxy group at position 4 of the anthracycline structure gives the compound a high lipophilicity which results in an increased rate of cellular uptake compared with other anthracyclines.Idarubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. Idarubicin in combination with other approved antileukemic drugs is indicated for the treatment of acute myeloid leukemia (AML) in adults.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA topoisomerase II alpha 37 Target ID: CHEMBL1806 Sources: https://www.drugbank.ca/drugs/DB01177 \| https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0a5a6d93-cc1e-4d7f-8da1-446c134503b3&type=display \| https://www.ncbi.nlm.nih.gov/pubmed/17616443 \| https://www.ncbi.nlm.nih.gov/pubmed/8036155	Inhibitor 8297
DNA 278 Target ID: CHEMBL2311221 Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0a5a6d93-cc1e-4d7f-8da1-446c134503b3&type=display \| https://www.drugbank.ca/drugs/DB01177 \| https://www.ncbi.nlm.nih.gov/pubmed/8036155	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute myeloid leukemia 136 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/050734s005lbl.pdf http://adisinsight.springer.com/drugs/800001995	Primary		Approved 8429	IDAMYCIN Approved Use IDAMYCIN PFS Injection in combination with other approved antileukemic drugs is indicated for the treatment of acute myeloid leukemia (AML) in adults. This includes French-American-British (FAB) classifications M1 through M7. Launch Date 1990

C_max

Value	Dose	Co-administered	Analyte	Population
7.7 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/12621462	40 mg/m² single, intravenous dose: 40 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		IDARUBICIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
423.2 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/12621462	40 mg/m² single, intravenous dose: 40 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		IDARUBICIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
38.8 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/12621462	40 mg/m² single, intravenous dose: 40 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		IDARUBICIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
3% DRUG LABEL https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/7c20b574-285b-49eb-a98e-6752e4bb481d/spl-doc?hl=IDARUBICIN			IDARUBICIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
18 mg/m2 1 times / day multiple, intravenous MTD Dose: 18 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 18 mg/m2, 1 times / day Co-administed with:: cytarabine(100 mg/m^2/day) Sources: https://pubmed.ncbi.nlm.nih.gov/26750985/	unhealthy, 23-60 n = 3 Health Status: unhealthy Condition: acute myeloid leukemia Age Group: 23-60 Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/26750985/	Other AEs: Neutropenia, Thrombocytopenia... Other AEs: Neutropenia (all grades, 3 patients) Thrombocytopenia (all grades, 3 patients) Mucositis (all grades, 3 patients) Anorexia (all grades, 3 patients) Diarrhea (all grades, 3 patients) Vomiting (all grades, 2 patients) Left ventricular systolic dysfunction (all grades, 2 patients) Cardiac arrhythmia (all grades, 1 patient) Rash (all grades, 2 patients) Infection (all grades, 3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/26750985/
15 mg/m2 1 times / day multiple, oral Dose: 15 mg/m2, 1 times / day Route: oral Route: multiple Dose: 15 mg/m2, 1 times / day Co-administed with:: metoclopramide(10 mg; 2/day) Sources: https://pubmed.ncbi.nlm.nih.gov/2208149/	unhealthy, 66 years (range: 40-85 years) n = 46 Health Status: unhealthy Condition: non-Hodgkin's lymphoma Age Group: 66 years (range: 40-85 years) Population Size: 46 Sources: https://pubmed.ncbi.nlm.nih.gov/2208149/	Other AEs: Nausea, Vomiting... Other AEs: Nausea (50%) Vomiting (50%) Mucositis (20%) Diarrhea (20%) Alopecia (15%) Anorexia (11%) Sepsis (2%) Hepatitis (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/2208149/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 CYP1A2 1524 MRP 7	CYP2C8 693 CYP1A2 1054

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15204103/	no
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15204103/	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15204103/	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15204103/	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15204103/	yes
MRP 7	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9188796/	yes
P-gp 1650	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/9063374/ \| https://pubmed.ncbi.nlm.nih.gov/15585622/	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15204103/	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15204103/	no
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15204103/	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15204103/	yes
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15204103/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:42068	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:42068
ChemicalBook	CB5283235	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5283235
ZINC	ZINC000003920266	http://zinc15.docking.org/substances/ZINC000003920266
eMolecules	539550	https://www.emolecules.com/cgi-bin/more?vid=539550

PubMed

Title	Date	PubMed
High-dose idarubicin and busulphan as conditioning for autologous stem cell transplantation in acute myeloid leukemia: a feasibility study.	2001	11920252
Autologous hematopoietic stem cell transplantation in chronic myeloid leukemia with different clinical stages.	2001	11713374
Acute basophilic leukemia.	2001 Aug	11722593
[CD7(+) acute myeloid leukemia (M0) associated with a mediastinal bulky mass lesion].	2001 Aug	11579505
Anthracycline-induced cardiomyopathy.	2001 Aug	11552224
Generation of reactive oxygen species is not involved in idarubicin-induced apoptosis in human leukaemic cells.	2001 Dec	11843815
Therapy-related myelodysplastic syndrome/acute myeloid leukemia M2 and translocation (8;21).	2001 Dec	11797121
Contribution of specific transport systems to anthracycline transport in tumor and normal cells.	2001 Dec	11766987
Idarubicin, cytarabine, and topotecan in patients with refractory or relapsed acute myelogenous leukemia and high-risk myelodysplastic syndrome.	2001 Dec	11754412
Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/- Ida) and second allogeneic stem cell transplant.	2001 Dec	11736947
Histopathologic features of retinoblastoma and its relation with in vitro drug resistance measured by means of the MTT assay.	2001 Dec 1	11753969
Comparison of idarubicin + ara-C-, fludarabine + ara-C-, and topotecan + ara-C-based regimens in treatment of newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts in transformation, or refractory anemia with excess blasts.	2001 Dec 15	11739159
Oligonucleotide enhanced cytotoxicity of Idarubicin for lymphoma cells.	2001 Jul	11699407
Cytosine arabinoside, idarubicin and divided dose etoposide for the treatment of acute myeloid leukemia in elderly patients.	2001 Jul	11699399
Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens.	2001 Jun	11551022
Development of hepatic veno-occlusive disease after Mylotarg infusion for relapsed acute myeloid leukemia.	2001 Nov	11781652
Influence of P-glycoprotein modulators on cardiac uptake, metabolism, and effects of idarubicin.	2001 Nov	11758760
And the sun keeps shining.	2001 Nov	11713460
Recent advances in the prevention of anthracycline cardiotoxicity in childhood.	2001 Nov	11562284
Anthracyclines: recent developments in their separation and quantitation.	2001 Nov 25	11817026
An adjustment for a post-randomization variable in the comparison of two treatments for survival.	2001 Nov 30	11746330
FAB M4 and high CD14 surface expression is associated with high cellular resistance to Ara-C and daunorubicin: implications for clinical outcome in acute myeloid leukaemia.	2001 Oct	11860442
A pharmacokinetic study of idarubicin in Japanese patients with malignant lymphoma: relationship with leukocytopenia and neutropenia.	2001 Oct	11721966
High dose of idarubicin-based regimen for diffuse large cell AIDS-related non-Hodgkin's lymphoma patients: a pilot study.	2001 Oct	11602411
Intensive timed sequential remission induction chemotherapy with high-dose cytarabine for childhood acute myeloid leukemia.	2001 Oct	11568900
High-dose chemotherapy in high-risk myelodysplastic syndrome: covariate-adjusted comparison of five regimens.	2001 Oct 15	11596013
Intensive chemotherapy followed by allogeneic or autologous stem cell transplantation for patients with myelodysplastic syndromes (MDSs) and acute myeloid leukemia following MDS.	2001 Oct 15	11588026
Spectroscopic studies on iron complexes of different anthracyclines in aprotic solvent systems.	2001 Oct 8	11578175
Pharmacokinetics and toxicity of idarubicin in the rat.	2001 Oct-Dec	11808862
Long-term follow-up of the clinical efficacy of chemotherapy for acute myeloid leukemia at a single institute.	2001 Sep	11810577
Granulomatous tubulointerstitial nephritis induced by all-trans retinoic acid.	2001 Sep	11604554
Synergism between fludarabine and rituximab revealed in a follicular lymphoma cell line resistant to the cytotoxic activity of either drug alone.	2001 Sep	11564066
Tolerance in baboon kidney transplantation with total lymphoid irradiation (TLI) and anti-CD3/CD4-idarubicin conjugates.	2001 Sep 27	11579315
A case of zygomycosis and invasive candidiasis involving the epiglottis and tongue in an immunocompromised patient.	2002	11928855
Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice.	2002	11813290
Automated differential counts in acute promyelocytic leukemia patients may be misleading.	2002 Apr	11920794
Comparison of idarubicin and daunorubicin regarding intracellular uptake, induction of apoptosis, and resistance.	2002 Apr 25	11867198
Diversity of the apoptotic response to chemotherapy in childhood leukemia.	2002 Feb	11840289
AIDA treatment for high-risk acute promyelocytic leukemia in a pregnant woman at 21 weeks of gestation.	2002 Feb	11836189
Retinoic acid syndrome: a case of massive lung consolidation.	2002 Feb	11836180
P-glycoprotein inhibitors enhance saturable uptake of idarubicin in rat heart: pharmacokinetic/pharmacodynamic modeling.	2002 Feb	11805234
Evaluation of the clinical relevance of the expression and function of P-glycoprotein, multidrug resistance protein and lung resistance protein in patients with primary acute myelogenous leukemia.	2002 Feb	11755464
Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes.	2002 Feb 28	11836027
[Acute myelogenous leukemia associated with severe esophageal stricture after chemotherapy].	2002 Jan	11868364
Secondary acute promyelocytic leukemia in a patient with non-Hodgkin's lymphoma treated with VP-16 and MST-16.	2002 Jan	11843282
Standard versus alternative myeloablative conditioning regimens in allogeneic hematopoietic stem cell transplantation for high-risk acute leukemia.	2002 Jan	11801465
Effects of cytarabine and various anthracyclins on platelet activation: characterization of in vitro effects and their possible clinical relevance in acute myelogenous leukemia.	2002 Jan 1	11774251
Cell-based assays for identification of novel double-strand break-inducing agents.	2002 Jan 16	11792746
Phase I trial with escalating doses of idarubicin and multidrug resistance reversal by short-course cyclosporin A, sequential high-dose cytosine arabinoside, and granulocyte colony-stimulating factor for adult patients with refractory acute leukemia.	2002 Mar	11869937
Multiple interference of anthracyclines with mitochondrial creatine kinases: preferential damage of the cardiac isoenzyme and its implications for drug cardiotoxicity.	2002 Mar	11854431

Patents

Sample Use Guides

In Vivo Use Guide

For induction therapy in adult patients with AML the following dose schedule is recommended: Idarubicin 12 mg/m2 daily for 3 days by slow (10 to 15 min) intravenous injection in combination with cytarabine. The cytarabine may be given as 100 mg/m2 daily by continuous infusion for 7 days or as cytarabine 25 mg/m2 intravenous bolus followed by cytarabine 200 mg/m2 daily for 5 days continuous infusion. In patients with unequivocal evidence of leukemia after the first induction course, a second course may be administered. Administration of the second course should be delayed in patients who experience severe mucositis, until recovery from this toxicity has occurred, and a dose reduction of 25% is recommended. In patients with hepatic and/or renal impairment, a dose reduction of IDAMYCIN PFS should be considered. Idarubicin should not be administered if the bilirubin level exceeds 5 mg%

Route of Administration: Intravenous

In Vitro Use Guide

Treatment of HL-60 cells with 1 uM Idarubicin for 2 h could not induce internucleosomal DNA fragmentation, however, a ladder of DNA fragment, characteristic of apoptosis, was observed after incubation for 4 h. After 10-h, extensive DNA degradation was observed. When HL-60 cells were incubated with different doses of Idarubicin for 8 h, the degree of DNA fragmentation increased at the higher concentration.

Name

Type

Language

IDARUBICIN HYDROCHLORIDE

Official Name

English

IDAMYCIN

Brand Name

English

IDARUBICIN HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

IDARUBICIN HYDROCHLORIDE [JAN]

Common Name

English

IDARUBICIN HYDROCHLORIDE [VANDF]

Common Name

English

IDARUBICIN HYDROCHLORIDE [USAN]

Common Name

English

Idarubicin hydrochloride [WHO-DD]

Common Name

English

IMI-30

Code

English

1S,3S)-3-ACETYL-1,2,3,4,6,11-HEXAHYDRO-3,5,12-TRIHYDROXY-6,11-DIOXO-1-NAPHTHACENYL 3-AMINO-2,3,6-TRIDEOXY-.ALPHA.-L-LYXO-HEXOPYRANOSIDE, HYDROCHLORIDE

Common Name

English

5,12-NAPHTHACENEDIONE, 9-ACETYL-7-((3-AMINO-2,3,6-TRIDEOXY-.ALPHA.-L-LYXO-HEXOPYRANOSYL)OXY)-7,8,9,10-TETRAHYDRO-6,9,11-TRIHYDROXYHYDROCHLORIDE, (7S-CIS)-

Common Name

English

IDARUBICIN HYDROCHLORIDE [USP-RS]

Common Name

English

NSC-256439

Code

English

IDARUBICIN HYDROCHLORIDE [MI]

Common Name

English

IDARUBICIN HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

IDARUBICIN HCL

Common Name

English

IMI 30

Code

English

IDARUBICIN HYDROCHLORIDE [MART.]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

55890