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Teniposide (VM-26)

Alias: VM26; NSC-122819; VM-26; HSDB 6546; NSC 122819; VM 26; HSDB-6546; NSC122819; HSDB6546; CCRIS 2058. Trade name: Vumon; Vehem. Abbreviations: EPT; PTG
Cat No.:V1406 Purity: ≥98%
Teniposide (VM-26;HSDB-6546;NSC-122819; CCRIS-2058; Vumon; Vehem; EPT; PTG)is a semisynthetic podophyllotoxin derivative and chemotherapeuticagent mainly used in the treatment of childhood acute lymphocytic leukemia (ALL).
Teniposide (VM-26)
Teniposide (VM-26) Chemical Structure CAS No.: 29767-20-2
Product category: Topoisomerase
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Teniposide (VM-26; HSDB-6546; NSC-122819; CCRIS-2058; Vumon; Vehem; EPT; PTG) is a semisynthetic podophyllotoxin derivative and chemotherapeutic agent mainly used in the treatment of childhood acute lymphocytic leukemia (ALL). It functions by combining with DNA and the enzyme topoisomerase II to form a ternary complex. This complex causes dose-dependent breaks in DNA, both single and double stranded, as well as protein cross-links, inhibition of DNA strand religation, and cytotoxicity. Teniposide acts during the cell cycle's late S or early G phases.

Biological Activity I Assay Protocols (From Reference)
Targets
Topoisomerase II
ln Vitro
Teniposide is a topoisomerase II inhibitor. Teniposide (VM-26, 0.15–45 mg/L) has an IC50 of 0.35 mg/L and inhibits Tca8113 cell proliferation in a dose-dependent manner. Tca8113 cells undergo apoptosis when exposed to 5 mg/L of Teniposide. Cells in Tca8113 cells are arrested at the G2/M phase by Teniposide (5.0 mg/L)[2]. With an IC50 of 1.3?±?0.34 μg/mL, Teniposide is active on patient-derived primary cultured glioma cells when the cells have a high level of miR-181b. In comparison to control cells, Teniposide-treated cells exhibit reduced viability, and when MDM2 is suppressed, the IC50 drops from 5.86?±?0.36 μg/mL to 2.90?±?0.35 μg/mL. Via the mediation of MDM2, Teniposide also reduces the viability of glioma cells expressing high levels of miR-181b[3].
ln Vivo
Teniposide (0.5 mg/kg, i.p.) profoundly raises the frequencies of micronucleated polychromatic erythrocytes (MNPCEs), a finding that is directly linked to bone marrow toxicity due to the significant suppression of bone marrow. The frequencies of BrdU-labeled sperm are significantly reduced by Teniposide (24 mg/kg, i.p.). Additionally, Teniposide (12, 24 mg/kg, i.p.) significantly induces disomic sperm in male mouse germ cells[1].
ADME/Pharmacokinetics
Absorption, Distribution and Excretion
From 4% to 12% of a dose is excreted in urine as parent drug. Fecal excretion of radioactivity within 72 hours after dosing accounted for 0% to 10% of the dose.
10.3 mL/min/m2
Teniposide was detected in intracerebral tumors at concentrations of 0.05-1.12 ug/g tissue in 11 patients given 100-150 mg/sq m teniposide 1.5-3 hr before tumor resection. The concentrations in adjacent normal brain tissue were low (< 0.9 ug/g tissue) in three patients and undetectable (< 0.05 ug/g tissue) in the others
Teniposide was detected in one patient who died three days after a cumulative intravenous dose of 576 mg, the highest concentrations occurring in the spleen, prostate, heart, large bowel, liver and pancreas.
It is not known whether teniposide is distributed into breast milk.
Elimination: Renal: 4 to 12% of a dose as unchanged teniposide. In a study of tritium-labeled teniposide in adults, 44% of the radiolabel (parent compound and metabolites) was recovered in urine within 120 hours after dosing. Fecal: 0 to 10% of a dose.
For more Absorption, Distribution and Excretion (Complete) data for TENIPOSIDE (6 total), please visit the HSDB record page.
Metabolism / Metabolites
In isolated human liver preparations, cytochrome P450 mixed-function isozymes catalysed metabolism of the (pendant) E-ring to O-demethylated and catechol metabolites. This metabolism was subsequently attributed primarily to CYP3A4 activity and to a lesser degree to CYP3A5. Peroxidase-mediated O-demethylation of teniposide has also been reported.
In children given teniposide, the main metabolite in serum and urine was reported to be the hydroxy acid, formed by opening of the lactone ring; the cis-isomer, which may be a degradation product formed during storage, was also detected. The aglycone, formed by loss of the glucopyranoside moiety, was not detected (Evans et al., 1982). The hydroxy acid has not been found in plasma or urine in other studies with high doses of teniposide, and no changes in the measured concentration of teniposide in these samples was found after incubation with glucuronidase, indicating formation of little or none of the proposed glucuronide metabolites (Holthuis et al., 1987). In another study, however, 6% of the administered dose of teniposide was excreted in the urine as parent drug over 24 h, and a further 8% as a proposed aglycone glucuronide, which was not formally identified.
In general, the effects of teniposide in mammalian cells in vitro occurred in the absence of exogenous metabolic activation. Various metabolic species of teniposide have been identified, but their mutagenic properties have not been studied.
Teniposide has known human metabolites that include Teniposide catechol.
Biological Half-Life
5 hours
Terminal half life: 5 hours. NOTE: Plasma teniposide concentrations decline biexponentially following intravenous infusion.
It has a multiphasic pattern of clearance from plasma. After distribution, half lives of 4 hours and 10 to 40 hours are observed.
Toxicity/Toxicokinetics
Interactions
Concurrent administration of ciclosporin at 5 mg/kg bw over 2 h, followed by 30 mg/kg bw over 48 h intravenously, increased the AUC for teniposide by 50%, due to a reduction in clearance. Conversely, concurrent administration of phenytoin increased the clearance rate of teniposide to 32 mL/min per m2 from 13 mL/min per m2 for control patients.
References

[1]. Molecular cytogenetic evaluation of the aneugenic effects of teniposide in somatic and germinal cells of male mice. Mutagenesis. 2012 Jan;27(1):31-9.

[2]. Topoisomerase II trapping agent teniposide induces apoptosis and G2/M or S phase arrest of oral squamous cell carcinoma. World J Surg Oncol. 2006 Jul 6;4:41.

[3]. MiR-181b sensitizes glioma cells to teniposide by targeting MDM2. BMC Cancer. 2014 Aug 25;14:611.

Additional Infomation
Teniposide can cause developmental toxicity according to state or federal government labeling requirements.
Teniposide is a semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle.
Teniposide is a Topoisomerase Inhibitor. The mechanism of action of teniposide is as a Topoisomerase Inhibitor.
Teniposide is a semisynthetic derivative of podophyllotoxin with antineoplastic activity. Teniposide forms a ternary complex with the enzyme topoisomerase II and DNA, resulting in dose-dependent single- and double-stranded breaks in DNA, DNA: protein cross-links, inhibition of DNA strand religation, and cytotoxicity. This agent acts in the late S or early G phase of the cell cycle. (NCI04)
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle.
Drug Indication
Teniposide is used for the treatment of refractory acute lymphoblastic leukaemia
Mechanism of Action
The mechanism of action appears to be related to the inhibition of type II topoisomerase activity since teniposide does not intercalate into DNA or bind strongly to DNA. Teniposide binds to and inhibits DNA topoisomerase II. 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.
It is an inhibitor of DNA topoisomerase II enzymes: Teniposide is a DNA topoisomerase II poison that has been shown to promote DNA cleavage, with a strong preference for a C or T at position -1. Most of the mutational events reported in mammalian cells, including point mutations, chromosomal deletions and exchanges and aneuploidy, can be explained by this activity. Teniposide does not inhibit bacterial topoisomerases and may not mutate bacterial cells by the same mechanism as mammalian cells. Unlike many other DNA topoisomerase II poisons, teniposide does not bind to DNA, either covalently or by intercalation. Instead, it appears to interact directly with the DNA topoisomerase II enzyme.
... The drug appears to produce its cytotoxic effects by damaging DNA and thereby inhibiting or altering DNA synthesis. Teniposide has been shown to induce single-stranded DNA breaks; the drug also induces double-stranded DNA breaks and DNA-protein cross links. ... Teniposide appears to be cell cycle specific, inducing G2-phase arrest and preferentially killing cells in the G2 and late S phases.
Therapeutic Uses
Antineoplastic Agents; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors
Teniposide is indicated, in combination with other approved anticancer agents, for induction therapy of refractory childhood acute lymphocytic (lymphoblastic) leukemia. /Included in US product labeling/
Teniposide is indicated as a single agent or in combination for therapy of refractory non-Hodgkin's lymphoma. /NOT included in US product labeling/
Teniposide is indicated as a single agent or in combination for therapy of refractory neuroblastoma. /NOT included in US product labeling/
Drug Warnings
Since patients with Down's syndrome and leukemia may be particularly sensitive to myelosuppressive chemotherapy, initial dosage of teniposide should be reduced in such patients.
There currently is insufficient experience with teniposide therapy in patients with impaired renal and/or hepatic function to make specific recommendations for dosage adjustment. However, the possibility that adjustment in teniposide dosage may be necessary in such patients should be considered.
The major and dose-limiting adverse effect of teniposide is hematologic toxicity. Myelosuppression, which is dose related, can be severe when teniposide is used in combination with other chemotherapeutic agents for the treatment of acute lymphocytic leukemia (ALL). Early onset of profound myelosuppression with delayed recovery can be expected when using the doses and schedules of teniposide necessary for the treatment of refractory ALL, since bone marrow hypoplasia is a desired endpoint of therapy. Severe myelosuppression with resulting infection and bleeding may occur in patients receiving the drug. Infection and bleeding have occurred in about 12 and 5%, respectively, of pediatric patients receiving teniposide monotherapy.
Pregnancy risk category: D /POSITIVE EVIDENCE OF RISK. Studies in humans, or investigational or post-marketing data, have demonstrated fetal risk. Nevertheless, potential benefits from the use of the drug may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective./
For more Drug Warnings (Complete) data for TENIPOSIDE (18 total), please visit the HSDB record page.
Pharmacodynamics
Teniposide is a phase-specific cytotoxic drug, acting in the late S or early G 2 phase of the cell cycle. Teniposide prevents cell mitosis by causing single and double stranded DNA breaks as well as cross linking between protein and DNA.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C32H32O13S
Molecular Weight
656.65
Exact Mass
656.156
Elemental Analysis
C, 58.53; H, 4.91; O, 31.67; S, 4.88
CAS #
29767-20-2
Related CAS #
29767-20-2
PubChem CID
452548
Appearance
White to off-white solid powder
Density
1.6±0.1 g/cm3
Boiling Point
864.3±65.0 °C at 760 mmHg
Melting Point
274 - 277ºC
Flash Point
476.5±34.3 °C
Vapour Pressure
0.0±0.3 mmHg at 25°C
Index of Refraction
1.697
LogP
1.71
Hydrogen Bond Donor Count
3
Hydrogen Bond Acceptor Count
14
Rotatable Bond Count
6
Heavy Atom Count
46
Complexity
1090
Defined Atom Stereocenter Count
10
SMILES
S1C([H])=C([H])C([H])=C1C1([H])OC([H])([H])[C@]2([H])[C@]([H])([C@@]([H])([C@]([H])([C@@]([H])(O2)OC2([H])C3=C([H])C4=C(C([H])=C3[C@@]([H])(C3C([H])=C(C(=C(C=3[H])OC([H])([H])[H])O[H])OC([H])([H])[H])[C@@]3([H])C(=O)OC([H])([H])C32[H])OC([H])([H])O4)O[H])O[H])O1
InChi Key
NRUKOCRGYNPUPR-QBPJDGROSA-N
InChi Code
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
Chemical Name
(5S,5aR,8aR,9R)-5-[[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-thiophen-2-yl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one
Synonyms
VM26; NSC-122819; VM-26; HSDB 6546; NSC 122819; VM 26; HSDB-6546; NSC122819; HSDB6546; CCRIS 2058. Trade name: Vumon; Vehem. Abbreviations: EPT; PTG
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.
Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~40 mg/mL (~60.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (3.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.5229 mL 7.6144 mL 15.2288 mL
5 mM 0.3046 mL 1.5229 mL 3.0458 mL
10 mM 0.1523 mL 0.7614 mL 1.5229 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
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Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
Recruiting Completed Drug: Teniposide HLH Beijing Friendship Hospital October 22, 2023 Not Applicable
NCT00004916 Completed Drug: teniposide
Drug: paclitaxel
Lymphoma Northwestern University February 1999 Phase 1
Phase 2
NCT00186875 Completed Drug: methotrexate, teniposide,
PEG-asparaginase
Drug: L-asparaginase, erwinia
asparaginase
Acute Lymphoblastic Leukemia
Lymphoma, Lymphoblastic
St. Jude Children's Research
Hospital
November 2003 Phase 2
NCT00184041 Completed Drug: Daunorubicin, Vincristine,
Prednisone, Methotrexate, PEG-
Asparaginase, 6-Mercaptopurine,
Cytoxan, Cytosine Arabinoside,
VM-26 and 6-Thioguanine
Acute Lymphoblastic Leukemia St. Jude Children's Research
Hospital
July 2004 Phase 2
Biological Data
  • MiR-181b level is positively related to glioma cell sensitivity to teniposide. BMC Cancer . 2014 Aug 25:14:611.
  • Downregulation of MDM2 promotes cell sensitivity to teniposide. BMC Cancer . 2014 Aug 25:14:611.
  • Upregulation of miR-181b enhances cell sensitivity to teniposide through mediation of MDM2. BMC Cancer. 2014 Aug 25:14:611.
  • Illustration of the contribution of clastogenicity and aneugenicity to the induced MN frequencies in animals treated with colchicine (2 mg/kg), mitomycin C (2 mg/kg) and teniposide (0.5 mg/kg). Mutagenesis . 2012 Jan;27(1):31-9.
  • Time course of appearance of BrdU-labelled sperm in the epididymis after treatment with 24 mg/kg teniposide. *P < 0.05, **P < 0.01 compared with the concurrent control (Mann–Whitney U-test). Mutagenesis . 2012 Jan;27(1):31-9.
  • Dose–response curves of the frequencies of abnormal sperm from mice after treatment with teniposide. *P < 0.05, **P < 0.01 compared with the concurrent control (Mann–Whitney U-test). Mutagenesis . 2012 Jan;27(1):31-9.
  • Dose–response curves of the frequencies of abnormal sperm from mice 23 days after the last treatment with teniposide (daily exposure for 12 consecutive days). Mutagenesis . 2012 Jan;27(1):31-9.
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