Naxtarubicin

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H25IO11
Molecular Weight	640.3746
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@H]1O[C@@H](O[C@H]2C[C@@](O)(CC3=C2C(O)=C4C(=O)C5=CC=CC=C5C(=O)C4=C3O)C(=O)CO)[C@H](I)[C@H](O)[C@H]1O

InChI

InChIKey=CIDNKDMVSINJCG-GKXONYSUSA-N

InChI=1S/C26H25IO11/c1-9-19(30)24(35)18(27)25(37-9)38-13-7-26(36,14(29)8-28)6-12-15(13)23(34)17-16(22(12)33)20(31)10-4-2-3-5-11(10)21(17)32/h2-5,9,13,18-19,24-25,28,30,33-36H,6-8H2,1H3/t9-,13-,18+,19-,24-,25-,26-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C26H25IO11
Molecular Weight	640.3746
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	7 / 7
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23763920 | https://www.drugbank.ca/drugs/DB06420 | https://www.healio.com/hematology-oncology/leukemia/news/online/%7B59c6cf34-2eec-4605-a347-f477d91a927d%7D/fda-grants-fast-track-designation-to-annamycin-for-relapsedrefractory-acute-myeloid-leukemia

Annamycin is a highly lipophilic form of the anthracycline doxorubicin with the ability to bypass multidrug resistance mechanisms of cellular drug resistance. Annamycin belongs to the anthracycline class of drugs, and has a pleiotropic mechanism of action where it targets topoisomerase II, causing strand breaks in DNA. Annamycin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. The agent is being evaluated in separate phase 1 and phase 2 trials in the United States and Europe. Studies in animal models showed the agent to be noncardiotoxic. Trials that included patients with leukemia showed the agent was associated with fewer dose-limiting toxicities than typically experienced with doxorubicin. The FDA granted fast track designation to Annamycin for treatment of patients with relapsed or refractory acute myeloid leukemia.

Originator

Approval Year

PubMed

Title	Date	PubMed
NFkappaB activation and drug sensitivity in human neoplastic cells treated with anthracyclines.	2008-08-01	18666436
Cationic nanoparticles for delivery of amphotericin B: preparation, characterization and activity in vitro.	2008-05-07	18462496
Emerging therapeutic options for Philadelphia-positive acute lymphocytic leukemia.	2007-03	17355221
Effect of structural modification at the 4, 3', and 2' positions of doxorubicin on topoisomerase II poisoning, apoptosis, and cytotoxicity in human melanoma cells.	2007-01-23	17557149
Treatment of acute lymphoblastic leukaemia : a new era.	2007	17927282
Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential.	2006	17717971
ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal.	2005-10-04	16202168
Relationship between topoisomerase II-DNA cleavable complexes, apoptosis and cytotoxic activity of anthracyclines in human cervix carcinoma cells.	2005-09-15	16158963
Enhanced topoisomerase II targeting by annamycin and related 4-demethoxy anthracycline analogues.	2004-11	15542779
Phase II study of liposomal annamycin in the treatment of doxorubicin-resistant breast cancer.	2002-07	12111105
Mechanisms of transport across cell membranes of complexes contained in antitumour drugs.	2001-07-17	11427347
Aronex Pharmaceuticals reports on annamycin phase I trial.	2001-06	12113129
Effects of liposome-entrapped annamycin in human breast cancer cells: interference with cell cycle progression and induction of apoptosis.	2001	11180394

Patents

Sample Use Guides

In Vivo Use Guide

Solid tumors: a total of 51 courses were administered at doses of 2.5, 5, 10, 16.5, 21, 25 and 30 mg/m(2) in one, three, one, three, six, six and one patient respectively. Grade 2 infusional hypertension, anemia, and dizziness were noted at 16.5 mg/m(2). At 25 mg/m(2), two of six evaluable patients had DLT. DLT was grade 4 constipation, neutropenia and grade 3 nausea/vomiting. At 21 mg/m(2) one of six evaluable patients had DLT (grade 3 nausea/vomiting). This dose was the MTD. The recommended phase II dose is 21 mg/m(2).

Route of Administration: Intravenous

Substance Class	Chemical Created by `admin` on `Mon Mar 31 19:52:50 GMT 2025` Edited by `admin` on `Mon Mar 31 19:52:50 GMT 2025`
Record UNII	SNU299M83Q
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Naxtarubicin

Official Name

English

5,12-Naphthacenedione, 7-[(2,6-dideoxy-2-iodo-a-L-mannopyranosyl)oxy]-7,8,9,10-tetrahydro-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-, (7S,9S)-

Preferred Name

English

7-[(2,6-dideoxy-2-iodo-a-L-mannopyranosyl)oxy]-6,9,11-trihydroxy-9-(hydroxyacetyl)-7,8,9,10-tetrahydrotetracene-5,12-dione

Systematic Name

English

NAXTARUBICIN [USAN]

Common Name

English

Annamycin

Common Name

English

(7S,9S)-7-[(2,6-dideoxy-2-iodo-?-L-mannopyranosyl)oxy]-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-7,8,9,10-tetrahydrotetracene-5,12-dione

Systematic Name

English

C2632

Code

English

naxtarubicin [INN]

Common Name

English

Annamycin [WHO-DD]

Common Name

English

2'-IODO-3'-HYDROXY-4'-EPI-4-DEMETHOXYDOXORUBICIN

Common Name

English

C-2632

Code

English

(7S,9S)-7-[(2,6-Dideoxy-2-iodo-?-L-mannopyranosyl)oxy]-7,8,9,10-tetrahydro-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-5,12-naphthacenedione

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

787720