Topotecan

Topotecan

Clinical data
Trade names	Hycamtin
AHFS/Drugs.com	Monograph
MedlinePlus	a610007
Pregnancy category	AU: D US: D (Evidence of risk)
Routes of administration	Intravenous infusion, oral (capsules)
ATC code	L01XX17 (WHO)
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	31.4 % in humans
Protein binding	35%
Metabolism	Hepatic
Biological half-life	2–3 hours
Excretion	Renal
Identifiers
IUPAC name (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
CAS Number	123948-87-8 N
PubChem CID	60700
IUPHAR/BPS	7101
DrugBank	DB01030 Y
ChemSpider	54705 Y
UNII	7M7YKX2N15
KEGG	D08618 Y
ChEMBL	CHEMBL84 Y
ECHA InfoCard	100.121.013
Chemical and physical data
Formula	C23H23N3O5 •HCl
Molar mass	457.9 g/mol
3D model (Jmol)	Interactive image
SMILES O=C\1N4\C(=C/C2=C/1COC(=O)[C@]2(O)CC)c3nc5c(cc3C4)c(c(O)cc5)CN(C)C
InChI 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 Y Key:UCFGDBYHRUNTLO-QHCPKHFHSA-N Y
NY (what is this?)

Topotecan (trade name Hycamtin) is a chemotherapeutic agent that is a topoisomerase inhibitor. It is a synthetic, water-soluble analog of the natural chemical compound camptothecin. It is used in the form of its hydrochloride salt to treat ovarian cancer, lung cancer and other cancer types.

After GlaxoSmithKline received final FDA approval for Hycamtin Capsules on October 15, 2007, topotecan became the first topoisomerase I inhibitor for oral use.

As of 2016 experiments were under way for Neuroblastoma, Brainstem glioma, Ewing's sarcoma and Angelman's syndrome. In addition, topotecan is experimentally treating Non-small cell lung cancer, Colorectal Cancer, Breast cancer, Non-Hodgkin Lymphoma, Endometrial cancer, and Oligodendroglioma.

Angelman’s syndrome is a neuro-genetic disorder characterized by severe developmental delays, seizures, speech impairments and physical impairments. It is an epigenetic disease and other treatments focus on symptoms. It is caused by a deletion or mutation of the maternal allele for the ubiquitin protein ligase E3A.UBE3A is expressed in most body tissues. However, in neurons only the maternal copy of the gene is expressed. UBE3A is located on chromosome 15 and the paternal copy for the gene is genetically imprinted and is silenced by an antisense RNA transcript. The maternal copy control center of the gene is methylated, suppressing transcription in the antisense direction while the paternal copy control center is unmethylated.