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Details

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

SHOW SMILES / InChI
Structure of TOPOTECAN

SMILES

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

InChI

InChIKey=UCFGDBYHRUNTLO-QHCPKHFHSA-N
InChI=1S/C23H23N3O5/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/t23-/m0/s1

HIDE SMILES / InChI

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
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
Phase II and pharmacokinetic/pharmacodynamic trial of sequential topoisomerase I and II inhibition with topotecan and etoposide in advanced non-small-cell lung cancer.
2001
Treatment of extensive stage small cell lung cancer.
2001
Effect of hemodialysis on topotecan disposition in a patient with severe renal dysfunction.
2001
Topotecan and gemcitabine in platinum/paclitaxel-resistant ovarian cancer.
2001
Treatment of patients with metastatic germ cell tumors relapsing after high-dose chemotherapy.
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
Determination of topotecan by ELISA.
2001 Apr
Radiosensitization of tumor-targeted radioimmunotherapy with prolonged topotecan infusion in human breast cancer xenografts.
2001 Apr 1
Unusual potency of BN 80915, a novel fluorinated E-ring modified camptothecin, toward human colon carcinoma cells.
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
Clinical evidence for topotecan-paclitaxel non--cross-resistance in ovarian cancer.
2001 Apr 1
Topotecan versus observation after cisplatin plus etoposide in extensive-stage small-cell lung cancer: E7593--a phase III trial of the Eastern Cooperative Oncology Group.
2001 Apr 15
A mutation in subunit B of the DNA polymerase alpha-primase complex from Novikoff hepatoma cells concomitant with a conformational change and abnormal catalytic properties of the DNA polymerase alpha-primase complex.
2001 Aug
Pharmacodynamic model of topotecan-induced time course of neutropenia.
2001 Aug
Combination antiangiogenic therapy: increased efficacy in a murine model of Wilms tumor.
2001 Aug
Phase I clinical trial of weekly combined topotecan and irinotecan.
2001 Aug
Resistance to topoisomerase poisons due to loss of DNA mismatch repair.
2001 Aug 15
Lack of efficacy of topotecan in the treatment of metastatic or recurrent squamous carcinoma of the head and neck: an Eastern Cooperative Oncology Group Trial (E3393).
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
P53 modulates the effect of loss of DNA mismatch repair on the sensitivity of human colon cancer cells to the cytotoxic and mutagenic effects of cisplatin.
2001 Feb 15
Phase I study of topotecan plus cranial radiation for glioblastoma multiforme: results of Radiation Therapy Oncology Group Trial 9507.
2001 Feb 15
Current treatment for ovarian cancer.
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
Up-front window trial of topotecan in previously untreated children and adolescents with metastatic rhabdomyosarcoma: an intergroup rhabdomyosarcoma study.
2001 Jan 1
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
Paclitaxel plus topotecan treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.
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
Topotecan selectively enhances the radioresponse of human small-cell lung carcinoma and glioblastoma multiforme xenografts in nude mice.
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
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
Characterization of a novel topoisomerase I mutation from a camptothecin-resistant human prostate cancer cell line.
2001 Mar 1
Phase I pharmacokinetic trial and correlative in vitro phase II tumor kinetic study of Apomine (SR-45023A), a novel oral biphosphonate anticancer drug.
2001 May
A weekly regimen of cisplatin, paclitaxel and topotecan with granulocyte-colony stimulating factor support for patients with extensive disease small cell lung cancer: a phase II study.
2001 May 4
High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support: a new regimen for the treatment of advanced ovarian cancer.
2001 Sep
Body-surface area-based dosing does not increase accuracy of predicting cisplatin exposure.
2001 Sep 1
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 20:27:45 UTC 2019
Edited
by admin
on Mon Oct 21 20:27:45 UTC 2019
Record UNII
7M7YKX2N15
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TOPOTECAN
EMA EPAR   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
NOGITECAN
Common Name English
TOPOTECAN [INN]
Common Name English
NSC-609699
Code English
TOPOTECAN [VANDF]
Common 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-, (4S)-
Systematic Name English
10-HYDROXY-9-((DIMETHYLAMINO)METHYL)-(20S)-CAMPTOTHECIN
Common Name English
TOPOTECAN [EMA EPAR]
Common Name English
HYCAMPTAMINE
Common Name English
TOPOTECAN [WHO-DD]
Common Name English
SK&F-104864
Code English
HYCAMPTIN
Brand Name English
TOPOTECAN [MI]
Common Name English
SKF-104864
Code English
Classification Tree Code System Code
WHO-VATC QL01XX17
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
EMA ASSESSMENT REPORTS POTACTASOL (AUTHORISED: SMALL CELL LUNG CARCINOMA, UTERINE CERVICAL NEOPLASMS)
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
EMA ASSESSMENT REPORTS HYCAMTIN (AUTHORIZED: OVARIAN NEOPLASMS, SMALL CELL LUNG CARCINOMA, UTERINE CERVICAL NEOPLASMS)
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
EMA ASSESSMENT REPORTS EVOTOPIN (WITHDRAWN: OVARIAN NEOPLASMS
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
LIVERTOX 982
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
EMA ASSESSMENT REPORTS TOPOTECAN HOSPIRA (AUTHORISED: SMALL CELL LUNG CARCINOMA)
Created by admin on Mon Oct 21 20:27:46 UTC 2019 , Edited by admin on Mon Oct 21 20:27:46 UTC 2019
EMA ASSESSMENT REPORTS TOPOTECAN ACTAVIS (AUTHORISED: SMALL CELL LUNG CARCINOMA, UTERINE NEOPLASMS )
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
NDF-RT N0000000176
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
EMA ASSESSMENT REPORTS TOPOTECAN TEVA (AUTHORIZED: OVARIAN NEOPLASMS, SMALL CELL LUNG CARCINOMA, UTERINE CERVICAL NEOPLASMS)
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
NDF-RT N0000175609
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
WHO-ATC L01XX17
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
NCI_THESAURUS C2843
Created by admin on Mon Oct 21 20:27:46 UTC 2019 , Edited by admin on Mon Oct 21 20:27:46 UTC 2019
Code System Code Type Description
INN
6783
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
PRIMARY
NCI_THESAURUS
C1413
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
PRIMARY
HSDB
123948-87-8
Created by admin on Mon Oct 21 20:27:46 UTC 2019 , Edited by admin on Mon Oct 21 20:27:46 UTC 2019
PRIMARY
MERCK INDEX
M10977
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
PRIMARY Merck Index
IUPHAR
7101
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
PRIMARY
EVMPD
SUB11191MIG
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
PRIMARY
ChEMBL
CHEMBL84
Created by admin on Mon Oct 21 20:27:46 UTC 2019 , Edited by admin on Mon Oct 21 20:27:46 UTC 2019
PRIMARY
WIKIPEDIA
Topotecan
Created by admin on Mon Oct 21 20:27:46 UTC 2019 , Edited by admin on Mon Oct 21 20:27:46 UTC 2019
PRIMARY
PUBCHEM
60700
Created by admin on Mon Oct 21 20:27:46 UTC 2019 , Edited by admin on Mon Oct 21 20:27:46 UTC 2019
PRIMARY
RXCUI
57308
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
PRIMARY RxNorm
MESH
D019772
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
PRIMARY
CAS
123948-87-8
Created by admin on Mon Oct 21 20:27:45 UTC 2019 , Edited by admin on Mon Oct 21 20:27:45 UTC 2019
PRIMARY
EPA CompTox
123948-87-8
Created by admin on Mon Oct 21 20:27:46 UTC 2019 , Edited by admin on Mon Oct 21 20:27:46 UTC 2019
PRIMARY
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