BELOTECAN HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H27N3O4.ClH
Molecular Weight	469.961
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CC[C@@]1(O)C(=O)OCC2=C1C=C3N(CC4=C(CCNC(C)C)C5=CC=CC=C5N=C34)C2=O

InChI

InChIKey=SJKBXKKZBKCHET-UQIIZPHYSA-N

InChI=1S/C25H27N3O4.ClH/c1-4-25(31)19-11-21-22-17(12-28(21)23(29)18(19)13-32-24(25)30)15(9-10-26-14(2)3)16-7-5-6-8-20(16)27-22;/h5-8,11,14,26,31H,4,9-10,12-13H2,1-3H3;1H/t25-;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9875499

Belotecan is a semisynthetic analogue of camptothecin containing a 2-(N-isopropylamino) ethyl group linkage at position C-7 of the camptothecin ring. It stabilizes the complex formed between topoisomerase I and DNA, thereby preventing the religation of DNA breaks. This leads to an inhibition of DNA replication and triggers apoptotic cell death. Belotecan was approved in Korea under the name Camtobell for the treatment of patients with ovarian and small cell lung cancers.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA topoisomerase 1 16 Target ID: P11387\|\|\|Q9UJN0 Gene ID: 7150.0 Gene Symbol: TOP1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/9875499	Inhibitor 8297		0.275 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ovarian cancer 157 Sources: http://www.kpbma.or.kr/attach/2016%20%EC%A0%9C%EC%95%BD%ED%98%91%ED%9A%8C%20%EC%98%81%EB%AC%B8%EB%94%94%EB%A0%89%ED%86%A0%EB%A6%AC_%EB%82%B4%EC%A7%80%EC%B5%9C%EC%A2%85.pdf	Primary		Approved 8429	CAMTOBELL Approved Use Ovarian cancer, SCLC Launch Date 2003
Small-cell lung cancer 41 Sources: http://www.kpbma.or.kr/attach/2016%20%EC%A0%9C%EC%95%BD%ED%98%91%ED%9A%8C%20%EC%98%81%EB%AC%B8%EB%94%94%EB%A0%89%ED%86%A0%EB%A6%AC_%EB%82%B4%EC%A7%80%EC%B5%9C%EC%A2%85.pdf	Primary		Approved 8429	CAMTOBELL Approved Use Ovarian cancer, SCLC Launch Date 2003

PubMed

Title	Date	PubMed
Preformulation studies of a novel camptothecin anticancer agent, CKD-602: physicochemical characterization and hydrolytic equilibrium kinetics.	2002 Jun 4	12052706
Evaluation of the toxic potentials of a new camptothecin anticancer agent CKD-602 on fertility and early embryonic development in rats.	2006 Aug	16814440
STEALTH liposomal CKD-602, a topoisomerase I inhibitor, improves the therapeutic index in human tumor xenograft models.	2007 Jul-Aug	17695551
Effect of probenecid on the biliary excretion of belotecan.	2007 Nov	18087819
Chemosensitivity of uterine cervical cancer demonstrated by the histoculture drug response assay.	2009 Dec	19966525
Apoptotic effect of CKD-602 (Camtobell) on oral squamous cell carcinoma cell lines.	2009 Mar	18715816
Pharmacokinetic study of pegylated liposomal CKD-602 (S-CKD602) in patients with advanced malignancies.	2009 Nov	19675541
Decreased urinary secretion of belotecan in folic acid-induced acute renal failure rats due to down-regulation of Oat1 and Bcrp.	2009 Oct	19552531
Multicenter phase 2 study of belotecan, a new camptothecin analog, and cisplatin for chemotherapy-naive patients with extensive-disease small cell lung cancer.	2010 Jan 1	19904804
Durable response after just one cycle of belotecan-based chemotherapy in a patient with relapsed primary peritoneal serous carcinoma.	2014 Jan	24102892

Patents

Sample Use Guides

In Vivo Use Guide

Small cell lung cancer: 0.5mg/m2/day for day 1 to 4. Ovarian cancer: 0.5mg/m2 IV days 1, 2, 3, 4, 5 of each 21 day cycle until 6 cycle or disease progression.

Route of Administration: Intravenous

In Vitro Use Guide

In a cell viability assay, human glioblastoma cell lines (U87 MG, U251 MG, U343 MG, LN229) were plated in 96-well plates at a density of 2x10(3) cells/well (100 ul). In each experimental set, cells were plated in quadruplicate and were treated with different concentrations (0.05, 0.1, 0.2, 0.5, 1, 2, 5 uM) of belotecan for 24, 48 and 72 h. The IC50 values were 84.66 nM for U87 MG cells, 29.13 nM for U343 MG, 14.57 nM for U251 MG cells and 9.07 nM for LN229 cells at 48 h after treatment.

Name

Type

Language

BELOTECAN HYDROCHLORIDE

Official Name

English

BELOTECAN HYDROCHLORIDE [MI]

Common Name

English

BELOTECAN HCL

Common Name

English

BELOTECAN HYDROCHLORIDE [MART.]

Common Name

English

BELOTECAN HYDROCHLORIDE [USAN]

Common Name

English

1H-PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-3,14(4H,12H)-DIONE,4-ETHYL-4-HYDROXY-11(2-((1METHYLETHYL)-MONOHYDROCHLORIDE, (4S)-

Common Name

English

(4S)-4-ETHYL-4-HYDROXY-11-(2-((1-METHYLETHYL)AMINO)ETHYL)-1,12-DIHYDRO-14H-PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-3,14(4H)-DIONEHYDRODCHLORIDE

Common Name

English

CKD-602

Code

English

Belotecan hydrochloride [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2843