U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C23H23N3O5.ClH
Molecular Weight 457.907
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TOPOTECAN HYDROCHLORIDE

SMILES

Cl.CC[C@@]1(O)C(=O)OCC2=C1C=C3N(CC4=C3N=C5C=CC(O)=C(CN(C)C)C5=C4)C2=O

InChI

InChIKey=DGHHQBMTXTWTJV-BQAIUKQQSA-N
InChI=1S/C23H23N3O5.ClH/c1-4-23(30)16-8-18-20-12(9-26(18)21(28)15(16)11-31-22(23)29)7-13-14(10-25(2)3)19(27)6-5-17(13)24-20;/h5-8,27,30H,4,9-11H2,1-3H3;1H/t23-;/m0./s1

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C23H23N3O5
Molecular Weight 421.4458
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Topotecan, a semi-synthetic derivative of camptothecin (a plant alkaloid obtained from the Camptotheca acuminata tree), is an anti-tumor drug with topoisomerase I-inhibitory activity similar to irinotecan. DNA topoisomerases are enzymes in the cell nucleus that regulate DNA topology (3-dimensional conformation) and facilitate nuclear processes such as DNA replication, recombination, and repair. During these processes, DNA topoisomerase I creates reversible single-stranded breaks in double-stranded DNA, allowing intact single DNA strands to pass through the break and relieve the topologic constraints inherent in supercoiled DNA. The 3'-DNA terminus of the broken DNA strand binds covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the unaltered topoisomers that allow transcription to proceed. Topotecan interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells can be affected by the medicine, other effects may also occur. Unlike irinotecan, topotecan is found predominantly in the inactive carboxylate form at neutral pH and it is not a prodrug. Topotecan has the same mechanism of action as irinotecan and is believed to exert its cytotoxic effects during the S-phase of DNA synthesis. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. This ternary complex interferes with the moving replication fork, which leads to the induction of replication arrest and lethal double-stranded breaks in DNA. As mammalian cells cannot efficiently repair these double strand breaks, the formation of this ternary complex eventually leads to apoptosis (programmed cell death). Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (−1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme–substrate complex, Topotecan acts as an uncompetitive inhibitor. Topotecan is used for the treatment of advanced ovarian cancer in patients with disease that has recurred or progressed following therapy with platinum-based regimens. Also used as a second-line therapy for treatment-sensitive small cell lung cancer, as well as in combination with cisplatin for the treatment of stage IV-B, recurrent, or persistent cervical cancer not amenable to curative treatment with surgery and/or radiation therapy. Topotecan is sold under the trade name Hycamtin.

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.448 µM [IC50]
1.1 µM [IC50]
33.0 nM [IC50]
1028.0 nM [IC50]
3.16 µM [IC50]
Conditions
PubMed

PubMed

TitleDatePubMed
Comparison of in vitro activities of camptothecin and nitidine derivatives against fungal and cancer cells.
1999 Dec
Camptothecin resistance: role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells.
1999 Dec 1
[Topotecan: a new field of use].
1999 Nov-Dec
Phase II study of oral topotecan in advanced non-small cell lung cancer.
2000 Mar
The inhibitory effects of camptothecin, a topoisomerase I inhibitor, on collagen synthesis in fibroblasts from patients with systemic sclerosis.
2001
Developmental chemotherapy in advanced ovarian cancer: incorporation of topoisomerase-I inhibitors and perspective of the Gynecologic Oncology Group.
2001
Topotecan and gemcitabine in platinum/paclitaxel-resistant ovarian cancer.
2001
ICE bioassay. Isolating in vivo complexes of enzyme to DNA.
2001
Antitumor activity of XR5944, a novel and potent topoisomerase poison.
2001 Apr
The association of topotecan and cytarabine in the treatment of secondary or relapsed acute myeloid leukemia.
2001 Apr
Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918.
2001 Apr
Radiosensitization of tumor-targeted radioimmunotherapy with prolonged topotecan infusion in human breast cancer xenografts.
2001 Apr 1
Identification of breast cancer resistant protein/mitoxantrone resistance/placenta-specific, ATP-binding cassette transporter as a transporter of NB-506 and J-107088, topoisomerase I inhibitors with an indolocarbazole structure.
2001 Apr 1
A prospective randomized phase II trial of GM-CSF priming to prevent topotecan-induced neutropenia in chemotherapy-naive patients with malignant melanoma or renal cell carcinoma.
2001 Apr 1
Topotecan given as a 21-day infusion in the treatment of advanced ovarian cancer.
2001 Apr 20
Pharmacodynamic model of topotecan-induced time course of neutropenia.
2001 Aug
Phase I clinical trial of weekly combined topotecan and irinotecan.
2001 Aug
Clonal heterogeneity of p53 mutations in ovarian cancer.
2001 Aug
A novel 7-modified camptothecin analog overcomes breast cancer resistance protein-associated resistance in a mitoxantrone-selected colon carcinoma cell line.
2001 Aug 15
Modulation of camptothecin analogs in the treatment of cancer: a review.
2001 Feb
Clear cell carcinoma of the ovary: a remarkable case.
2001 Feb
Topotecan concomitant with primary brachytherapy radiation in patients with cervical carcinoma: a phase I trial.
2001 Feb
P73a overexpression is associated with resistance to treatment with DNA-damaging agents in a human ovarian cancer cell line.
2001 Feb 1
Novel cytotoxic 7-iminomethyl and 7-aminomethyl derivatives of camptothecin.
2001 Feb 12
The effect of increasing topotecan infusion from 30 minutes to 4 hours on the duration of exposure in cerebrospinal fluid.
2001 Jan
Fludarabine, cytarabine and topotecan (FLAT) as induction therapy for acute myeloid leukemia in the elderly: a preliminary report.
2001 Jan
Response and toxicity to topotecan in sensitive ovarian cancer cases with small residual disease after first-line treatment with carboplatinum and paclitaxel.
2001 Jan
The HER tyrosine kinase inhibitor CI1033 enhances cytotoxicity of 7-ethyl-10-hydroxycamptothecin and topotecan by inhibiting breast cancer resistance protein-mediated drug efflux.
2001 Jan 15
Advances in the management of epithelial ovarian cancer.
2001 Jul
Topoisomerase I inhibitors in the treatment of head and neck cancer.
2001 Jul
Therapeutic activity of 7-[(2-trimethylsilyl)ethyl)]-20 (S)-camptothecin against central nervous system tumor-derived xenografts in athymic mice.
2001 Jul
Interaction between novel anticancer agents and radiation in non-small cell lung cancer cell lines.
2001 Jul
UCN-01 dose-dependent inhibition of normal hyperproliferative cells in mice.
2001 Jul
Effective dosing of topotecan with carboplatin in relapsed ovarian cancer: a phase I/II study.
2001 Jul 1
Antisense oligonucleotides targeting the epidermal growth factor receptor inhibit proliferation, induce apoptosis, and cooperate with cytotoxic drugs in human cancer cell lines.
2001 Jul 15
Sensitivity to topoisomerase I inhibitors and cisplatin is associated with epidermal growth factor receptor expression in human cervical squamous carcinoma ME180 sublines.
2001 Jun
Oligodendroglial ganglioglioma with anaplastic features arising from the thalamus.
2001 Jun
Temporary reversal by topotecan of marked insulin resistance in a patient with myelodysplastic syndrome: case report and possible mechanism for tumor necrosis factor alpha (TNF-alpha)-induced insulin resistance.
2001 Jun
Sodium phenylbutyrate induces apoptosis in human retinoblastoma Y79 cells: the effect of combined treatment with the topoisomerase I-inhibitor topotecan.
2001 Jun
Topoisomerase I inhibition with topotecan: pharmacologic and clinical issues.
2001 Mar
Development, characterization and therapy of a disseminated model of childhood neuroblastoma in SCID mice.
2001 Mar
Death receptor-independent cytochrome c release and caspase activation mediate thymidine kinase plus ganciclovir-mediated cytotoxicity in LN-18 and LN-229 human malignant glioma cells.
2001 Mar
Carrier and dose effects on the pharmacokinetics of T-0128, a camptothecin analogue-carboxymethyl dextran conjugate, in non-tumor- and tumor-bearing rats.
2001 Mar 12
Phase II trial of topotecan, carboplatin, and paclitaxel as front-line therapy in suboptimal advanced epithelial ovarian cancer.
2001 May
Repetitive high-dose topotecan, carboplatin, and paclitaxel with peripheral blood progenitor cell support in previously untreated ovarian cancer: results of a Phase I study.
2001 May
Topoisomerase IIalpha and other drug resistance markers in advanced non-small cell lung cancer.
2001 May
Synthesis and biological evaluation of novel A-ring modified hexacyclic camptothecin analogues.
2001 May 10
Advances in chemotherapy for small cell lung cancer: single-agent activity of newer agents.
2001 May-Jun
High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support: a new regimen for the treatment of advanced ovarian cancer.
2001 Sep
Patents

Sample Use Guides

In Vivo Use Guide
Ovarian cancer and small cell lung cancer: 1.5 mg/m2 by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day course. Cervical cancer: 0.75 mg/m2 by intravenous infusion over 30 minutes on Days 1, 2, and 3 repeated every 21 days in combination with cisplatin 50 mg/m2 on Day 1
Route of Administration: Intravenous
In Vitro Use Guide
In DC3F hamster lung fibroblasts, 2.5 uM topotecan caused redistribution of topo I to nonnucleolar regions of the nucleus.
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:59:40 UTC 2019
Edited
by admin
on Mon Oct 21 20:59:40 UTC 2019
Record UNII
956S425ZCY
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TOPOTECAN HYDROCHLORIDE
MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
TOPOTECAN ACTAVIS
Brand Name English
(S)-10-((DIMETHYLAMINO)METHYL)-4-ETHYL-4,9-DIHYDROXY-1H-PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-3,14(4H,12H)-DIONE MONOHYDROCHLORIDE
Systematic Name English
1H-PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-3,14(4H,12H)-DIONE, 10-((DIMETHYLAMINO)METHYL)-4-ETHYL-4,9-DIHYDROXY-, MONOHYDROCHLORIDE, (S)-
Common Name English
EVOTOPIN
Brand Name English
TOPOTECAN HYDROCHLORIDE [USAN]
Common Name English
SK&F S-104864-A
Code English
TOPOTECAN HYDROCHLORIDE [MI]
Common Name English
TOPOTECAN HYDROCHLORIDE [VANDF]
Common Name English
HYCAMTIN
Brand Name English
NOGITECAN HYDROCHLORIDE
JAN  
Common Name English
TOPOTECAN HYDROCHLORIDE [USP-RS]
Common Name English
TOPOTECAN (AS HYDROCHLORIDE)
Common Name English
TOPOTECAN HCL
Common Name English
TOPOTECAN HOSPIRA
Brand Name English
NOGITECAN HYDROCHLORIDE [JAN]
Common Name English
POTACTASOL
Brand Name English
TOPOTECAN HYDROCHLORIDE [ORANGE BOOK]
Common Name English
SK&F-S-104864-A
Code English
TOPOTECAN HYDROCHLORIDE [WHO-DD]
Common Name English
TOPOTECAN TEVA
Brand Name English
TOPOTECAN HYDROCHLORIDE [MART.]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 268508
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
EMA ASSESSMENT REPORTS POTACTASOL (AUTHORIZED: UTERINE CERVICAL NEOPLASMS)
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
EMA ASSESSMENT REPORTS TOPOTECAN TEVA (AUTHORIZED: UTERINE CERVICAL NEOPLASMS)
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
EMA ASSESSMENT REPORTS HYCAMTIN (AUTHORIZED: UTERINE CERVICAL NEOPLASMS)
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
EMA ASSESSMENT REPORTS TOPOTECAN EAGLE (WITHDRAWN SMALL CELL LUNG CARCINOMA)
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
EMA ASSESSMENT REPORTS TOPOTECAN TEVA (AUTHORIZED: OVARIAN NEOPLASMS)
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
EMA ASSESSMENT REPORTS EVOTOPIN (WITHDRAWN: OVARIAN NEOPLASMS)
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
NCI_THESAURUS C2843
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
EMA ASSESSMENT REPORTS TOPOTECAN ACTAVIS (AUTHORIZED: UTERINE CERVICAL NEOPLASMS)
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
EU-Orphan Drug EU/3/08/562
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
EMA ASSESSMENT REPORTS HYCAMTIN (AUTHORIZED: OVARIAN NEOPLASMS)
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
EMA ASSESSMENT REPORTS TOPOTECAN HOSPIRA (AUTHORIZED: UTERINE CERVICAL NEOPLASMS)
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
Code System Code Type Description
ChEMBL
CHEMBL84
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
PRIMARY
DRUG BANK
DB01030
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
PRIMARY
RXCUI
266573
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
PRIMARY RxNorm
CAS
119413-54-6
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
PRIMARY
EVMPD
SUB04921MIG
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
PRIMARY
NCI_THESAURUS
C2828
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
PRIMARY
MERCK INDEX
M10977
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
PRIMARY Merck Index
EPA CompTox
119413-54-6
Created by admin on Mon Oct 21 20:59:40 UTC 2019 , Edited by admin on Mon Oct 21 20:59:40 UTC 2019
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY