Teniposide

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Teniposide
Teniposide2DACS.svg
Clinical data
Trade names Vumon
Other namesVM-26
AHFS/Drugs.com Monograph
MedlinePlus a692045
Pregnancy
category
  • AU:D
Routes of
administration 		Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability N/A
Protein binding >99%
Metabolism Hepatic (CYP2C19-mediated)
Elimination half-life 5 hours
Excretion Renal and fecal
Identifiers
  • (5R,5aR,8aR,9S)-5,8,8a,9-Tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-9-({4,6-O-[(R)-2-thienylmethylene]-β-D-glucopyranosyl}oxy)furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.045.286 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C32H32O13S
Molar mass 656.66 g·mol−1
3D model (JSmol)
  • COc1cc(cc(c1O)OC)[C@@H]2c3cc4c(cc3[C@H]([C@@H]5[C@@H]2C(=O)OC5)O[C@H]6[C@@H]([C@H]([C@H]7[C@H](O6)COC(O7)c8cccs8)O)O)OCO4
  • InChI=1S/C32H32O13S/c1-37-19-6-13(7-20(38-2)25(19)33)23-14-8-17-18(42-12-41-17)9-15(14)28(16-10-39-30(36)24(16)23)44-32-27(35)26(34)29-21(43-32)11-40-31(45-29)22-4-3-5-46-22/h3-9,16,21,23-24,26-29,31-35H,10-12H2,1-2H3/t16-,21+,23+,24-,26+,27+,28+,29+,31?,32-/m0/s1 X mark.svgN
  • Key:NRUKOCRGYNPUPR-PSZSYXFXSA-N X mark.svgN
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Teniposide (trade name Vumon) is a chemotherapeutic medication [1] used in the treatment of childhood acute lymphocytic leukemia (ALL), Hodgkin's lymphoma, certain brain tumours, and other types of cancer. [2] It is in a class of drugs known as podophyllotoxin derivatives and slows the growth of cancer cells in the body. [3]

Contents

Medical uses

Teniposide is used for the treatment of a number of cancer types in children. In the US, it is approved for the second-line therapy of acute lymphocytic leukemia (ALL) in combination with other antineoplastic drugs. [3] In Europe, it is also approved for the treatment of Hodgkin's lymphoma, generalized malignant lymphoma, reticulocyte sarcoma, acute leukaemia, primary brain tumours (glioblastoma, ependymoma, astrocytoma), bladder cancer, neuroblastoma and other solid tumours in children. [2]

Administration

The medication is injected though a vein and burns if it leaks under the skin. It can be used in combination with other anticancer drugs. [2]

Contraindications

The drug is contraindicated during pregnancy and lactation, in patients with severe liver or kidney impairment or severely impaired haematopoiesis. [2]

Side effects

Teniposide, when used with other chemotherapeutic agents for the treatment of ALL, results in severe bone marrow suppression. Other common side effects include gastrointestinal toxicity, hypersensitivity reactions, and reversible alopecia. [2]

Interactions

No systematic interaction studies are available. The enzyme inducers phenobarbital and phenytoin have been found to lower its blood plasma concentrations. [4] Theoretically possible interactions include increased plasma concentrations when combined with sodium salicylate, sulfamethizole or tolbutamide, which displace teniposide from plasma protein binding, at least in vitro . [2] [3]

Pharmacology

Mechanism of action

Teniposide causes dose-dependent single- and double-stranded breaks in DNA and DNA-protein cross-links. [2] The substance has been found to act as an inhibitor of topoisomerase II (an enzyme that aids in DNA unwinding), [4] [5] since it does not intercalate into DNA or bind strongly to DNA. The cytotoxic effects of teniposide are related to the relative number of double-stranded DNA breaks produced in cells, which are a reflection of the stabilization of a topoisomerase II-DNA intermediate.[ citation needed ]

Chemistry

An illustration of the wild mandrake, showing part of the rhizome (at bottom) Podophyllum peltatum - Kohler-s Medizinal-Pflanzen-246.jpg
An illustration of the wild mandrake, showing part of the rhizome (at bottom)

Teniposide is a semisynthetic derivative of podophyllotoxin [2] from the rhizome of the wild mandrake (Podophyllum peltatum). More specifically, it is a glycoside of podophyllotoxin with a D-glucose derivative. It is chemically similar to the anti-cancer drug etoposide, being distinguished only by a thienyl rest where etoposide has a methyl. [4] Both these compounds have been developed with the aim of creating less toxic derivatives of podophyllotoxin. [6]

References

  1. ↑ Cragg GM, Newman DJ (August 2005). "Plants as a source of anti-cancer agents". Journal of Ethnopharmacology. 100 (1–2): 72–79. doi:10.1016/j.jep.2005.05.011. PMID   16009521.
  2. 1 2 3 4 5 6 7 8 Jasek W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 8855–6. ISBN   978-3-85200-181-4.
  3. 1 2 3 Drugs.com: Teniposide Monograph .
  4. 1 2 3 Mutschler E, Schäfer-Korting M (2001). Arzneimittelwirkungen (in German) (8th ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 894–5. ISBN   3-8047-1763-2.
  5. ↑ de Jong S, Kooistra AJ, de Vries EG, Mulder NH, Zijlstra JG (March 1993). "Topoisomerase II as a target of VM-26 and 4'-(9-acridinylamino)methanesulfon-m-aniside in atypical multidrug resistant human small cell lung carcinoma cells". Cancer Research. 53 (5): 1064–1071. PMID   8382551.
  6. ↑ Dinnendahl V, Fricke U, eds. (2015). Arzneistoff-Profile (in German). Vol. 4 (28th ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN   978-3-7741-9846-3.
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