123948-87-8 Usage
Camptothecin anticancer drugs
Camptothecin anticancer drugs are alkaloids or derivatives of them after the structure transformation raised from deciduous plant Davidia involucrata Camptotheca acuminate seed or root bark. Clinical application of them mainly includes camptothecin,hydroxycamptothecin, topotecan and irinotecan.
Topotecan is a water-soluble semi-synthetic derivative of camptothecin,it is a topoisomerase I inhibitor, inhibiting DNA single strand DNA scission reconnect to damage DNA, its cytotoxicity occurs in cancer cell division S phase, it is an s phase cell cycle specific drug . In vivo it is a two-compartment model,it can be quickly distributed to the liver, kidneys and other parts , of a single intravenous infusion 1.5mg/m2 every 30 minutes , t1/2αis 4.1 to 8.1 minutes, plasma protein binding rate is 6.6%~21.3%,it can go into the cerebrospinal fluid. Most of it is excreted by the kidneys, a small part of it is excreted by the bile, within 12 hours, 90% of it is excreted.Clearance rate of renal dysfunction decreases.it is clinically used for the treatment of small cell lung cancer (SCLC), and advanced ovarian cancer, because it can penetrate the blood-brain barrier ,it has a certain effect on the central nervous system cancer and brain metastases. Usage: every single drug dose 1.2mg/m2 intravenous infusion once a day, once every 5 days, 21 days is 1 cycle, there is the need to reduce the dose when in combination with other anticancer drugs. The main adverse events are hematologic toxicity, white blood cells, platelets and hemoglobin decrease; non-hematologic toxicity adverse events are loss of appetite, nausea, vomiting, hair loss, stomatitis, diarrhea, headache, fever, constipation, transient elevated transaminase; occasionally breathing difficulties, hematuria, andelectrocardiogram abnormalities.
Severe bone marrow suppression are hanged. Monitor the blood and adjust the dose in accordance with changes in blood during the treatment , if necessary, granulocyte colony stimulating factor (G-CSF), and transfusion of blood components may be given .
The above information is edited by the lookchem of Tian Ye.
Uses
Different sources of media describe the Uses of 123948-87-8 differently. You can refer to the following data:
1. Anti-cancer drugs.It can be used alone for the treatment of initially or continuously ineffective chemotherapy metastatic ovarian cancer.
2. antineoplastic;DNA topoisomerase type 1 inhibitor
3. (S)-Topotecan is a DNA topoisomerase I inhibitor; semisynthetic analog of Camptothecin. Antineoplastic. Topotecan hydrochloride is a chemotherapy agent that is a topoisomerase 1 inhibitor.
4. Topotecan has been used as a positive control for the identification and analysis of HIF-1α and VEGF inhibitors in human glioma cells under hypoxic conditions1. It has also been used for in vitro apoptosis assays in PA317 cells2.
Production methods
Compound (I) with 37% formaldehyde and 40% dimethylamine,after aminomethylation in acetic acid, produces the product.
Description
Topotecan was launched in the US for the second-line treatment of ovarian
cancer. It can be prepared in four steps from camptothecin and is a water soluble
derivative of the natural product with decreased toxicity. Unlike its chemical relative
irinotecan, topotecacan in not a prodrug and does not require bioactivation. It is an
inhibitor of topoisomerase I. Specifically, it inhibits the release of topoisomerase I
from DNA, where it relaxes supercoiled DNA, giving rise to single-strand breaks.
When the replication fork reaches this complex, double-stand breaks can occur. This
signals apoptosis and eventually gives rise to cell death. Evidence indicates
hycamtin is safe for people with impaired hepatic function.
Chemical Properties
Off-white Cryst
Originator
SmithKline Beecham (UK)
Definition
ChEBI: A pyranoindolizinoquinoline used as an antineoplastic agent. It is a derivative of camptothecin and works by binding to the topoisomerase I-DNA complex and preventing religation of these 328 single strand breaks.
Brand name
Hycamtin
Therapeutic Function
Antineoplastic
Biochem/physiol Actions
Topotecan is a topoisomerase I inhibitor and an apoptosis inducer. It is a potent antineoplastic agent.
Clinical Use
Antineoplastic agent: Treatment of metastatic ovarian, cervical and small cell lung cancer
Drug interactions
Potentially hazardous interactions with other drugs
None knownccccc
Metabolism
Topotecan undergoes reversible, pH-dependent hydrolysis of the active lactone moiety to the inactive hydroxyacid (carboxylate) form. A relatively small amount of topotecan is metabolised by hepatic microsomal enzymes to an active metabolite, N-demethyltopotecan; the clinical significance of this metabolite is not known. Excretion is via biliary and renal routes with 20-60% excreted in the urine as topotecan or the open ring form.
Check Digit Verification of cas no
The CAS Registry Mumber 123948-87-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,3,9,4 and 8 respectively; the second part has 2 digits, 8 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 123948-87:
(8*1)+(7*2)+(6*3)+(5*9)+(4*4)+(3*8)+(2*8)+(1*7)=148
148 % 10 = 8
So 123948-87-8 is a valid CAS Registry Number.
InChI:InChI=1/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
123948-87-8Relevant articles and documents
Aminoalkylation of 10-hydroxycamptothecin using methylene chloride under solid-liquid phase transfer catalysis: A new approach for the preparation of topotecan
Puri,Handa,Dhar,Suri,Qazi
, p. 2857 - 2862 (2004)
The use of dichloromethane as a reagent, for the preparation of Topotecan {(45)-10-(dimethylamino)methyl-4-ethyl-4,9-dihydroxy-1-H-pyrano[3′, 4′:6,7]indolizino-[1,2-b]quinoline-3,14(4H,12H)dione} from 10-hydroxy-camptothecin under solid-liquid phase transfer catalysis, which behaves both as a solvent and a reagent serving as for C-1 unit source for amino-alkylation of 10-hydroxy-(4S)-camptothecin.
THERAPEUTIC FOR HEPATIC CANCER
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, (2011/02/18)
A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.
Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same
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, (2010/05/13)
Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.
