Identification
- Generic Name
- Tesmilifene
- DrugBank Accession Number
- DB04905
- Background
Tesmilifene is a novel potentiator of chemotherapy which, when added to doxorubicin, achieved an unexpected and very large survival advantage over doxorubicin alone in a randomized trial in advanced breast cancer.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Tesmilifene (DB04905)
- Weight
- Average: 283.4079
Monoisotopic: 283.193614427 - Chemical Formula
- C19H25NO
- Synonyms
- N,N-diethyl-2-((4-phenylmethyl)phenoxy)ethanamine
- Tesmilifene
Pharmacology
- Indication
Intended for the treatment of various forms of cancer.
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Not Available
- Mechanism of action
Although the exact mechanism of action is not known, one study (PMID: 16413681) proposes that tesmilifene may be an activating p-gp substrate, which enables the p-gp pump to extrude typical p-gp substrates (such as anthracyclines or taxanes) more efficiently. This process consumes ATP, since the p-gp is absolutely, and highly dependent on ATP hydrolysis. The mechanism of cell death is likely to result not from the presence of chemotherapy inside the cell (in fact the chemotherapy is extruded) but, directly or indirectly, from the enhanced consumption of ATP. The ATP may be consumed below a threshold necessary for survival, or, (more likely) the enhanced ATP production required to maintain ATP levels may result in the generation of reactive oxygen species (ROS) to an extent that overwhelms the cell’s ability to inactivate them. The result would be additional cell death, but only in the mdr+ population. The doxorubicin would continue to act on the drug sensitive remainder of the cell population, but without the help of tesmilifene.
Target Actions Organism AP-glycoprotein 1 inducerHumans UHistamine H1 receptor antagonistHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Hepatic
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Tesmilifene can be increased when it is combined with Abametapir. Abatacept The metabolism of Tesmilifene can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Tesmilifene is combined with Abciximab. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Tesmilifene. Abiraterone The metabolism of Tesmilifene can be decreased when combined with Abiraterone. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Tesmilifene hydrochloride 1U4B477260 92981-78-7 TXLHNFOLHRXMAU-UHFFFAOYSA-N
Categories
- Drug Categories
- Antiplatelet agents
- Benzene Derivatives
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Ethers
- Hematologic Agents
- Histamine Agents
- Neurotransmitter Agents
- P-glycoprotein inducers
- P-glycoprotein inhibitors
- Phenols
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Diphenylmethanes
- Direct Parent
- Diphenylmethanes
- Alternative Parents
- Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Trialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- Alkyl aryl ether / Amine / Aromatic homomonocyclic compound / Diphenylmethane / Ether / Hydrocarbon derivative / Organic nitrogen compound / Organic oxygen compound / Organonitrogen compound / Organooxygen compound
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- I43T3ID6G2
- CAS number
- 98774-23-3
- InChI Key
- NFIXBCVWIPOYCD-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H25NO/c1-3-20(4-2)14-15-21-19-12-10-18(11-13-19)16-17-8-6-5-7-9-17/h5-13H,3-4,14-16H2,1-2H3
- IUPAC Name
- [2-(4-benzylphenoxy)ethyl]diethylamine
- SMILES
- CCN(CC)CCOC1=CC=C(CC2=CC=CC=C2)C=C1
References
- General References
- Liu J, Tu D, Dancey J, Reyno L, Pritchard KI, Pater J, Seymour LK: Quality of life analyses in a clinical trial of DPPE (tesmilifene) plus doxorubicin versus doxorubicin in patients with advanced or metastatic breast cancer: NCIC CTG Trial MA.19. Breast Cancer Res Treat. 2006 Dec;100(3):263-71. Epub 2006 Jul 6. [Article]
- Vincent M: Tesmilifene may enhance breast cancer chemotherapy by killing a clone of aggressive, multi-drug resistant cells through its action on the p-glycoprotein pump. Med Hypotheses. 2006;66(4):715-31. Epub 2006 Jan 18. [Article]
- Raghavan D, Brandes LJ, Klapp K, Snyder T, Styles E, Tsao-Wei D, Lieskovsky G, Quinn DI, Ramsey EW: Phase II trial of tesmilifene plus mitoxantrone and prednisone for hormone refractory prostate cancer: high subjective and objective response in patients with symptomatic metastases. J Urol. 2005 Nov;174(5):1808-13; discussion 1813. [Article]
- Brandes LJ, Queen GM, LaBella FS: N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine (DPPE) a chemopotentiating and cytoprotective agent in clinical trials: interaction with histamine at cytochrome P450 3A4 and other isozymes that metabolize antineoplastic drugs. Cancer Chemother Pharmacol. 2000;45(4):298-304. [Article]
- Brandes LJ, Hogg GR: Study of the in-vivo antioestrogenic action of N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl (DPPE), a novel intracellular histamine antagonist and antioestrogen binding site ligand. J Reprod Fertil. 1990 May;89(1):59-67. [Article]
- External Links
- PubChem Compound
- 108092
- PubChem Substance
- 175426896
- ChemSpider
- 97190
- BindingDB
- 50085260
- ChEBI
- 93414
- ChEMBL
- CHEMBL26424
- ZINC
- ZINC000000002139
- Wikipedia
- Tesmilifene
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 2 Completed Treatment Metastatic Breast Cancer 1 1 Completed Treatment Metastatic/Recurrent Breast Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00905 mg/mL ALOGPS logP 4.65 ALOGPS logP 4.64 Chemaxon logS -4.5 ALOGPS pKa (Strongest Basic) 9.33 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 12.47 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 89.77 m3·mol-1 Chemaxon Polarizability 33.95 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9935 Blood Brain Barrier + 0.9482 Caco-2 permeable + 0.8072 P-glycoprotein substrate Substrate 0.7041 P-glycoprotein inhibitor I Inhibitor 0.5341 P-glycoprotein inhibitor II Non-inhibitor 0.885 Renal organic cation transporter Inhibitor 0.7133 CYP450 2C9 substrate Non-substrate 0.7941 CYP450 2D6 substrate Substrate 0.6482 CYP450 3A4 substrate Substrate 0.5967 CYP450 1A2 substrate Inhibitor 0.9707 CYP450 2C9 inhibitor Inhibitor 0.5636 CYP450 2D6 inhibitor Inhibitor 0.9575 CYP450 2C19 inhibitor Inhibitor 0.6944 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8296 Ames test Non AMES toxic 0.5749 Carcinogenicity Non-carcinogens 0.657 Biodegradation Not ready biodegradable 0.9877 Rat acute toxicity 2.2808 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.7258 hERG inhibition (predictor II) Inhibitor 0.8407
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0f89-1790000000-e45616878dde7749104c Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0f89-9410000000-c0472932a2f3cac6d552 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-0190000000-73025847d44a8a8d74d2 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-008c-9400000000-ef3c321bf6dc3931b5f0 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-2910000000-fc3e03bc450ca2a74387 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-00lr-1900000000-28cc3d2b9edeeba08cac Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 185.0617415 predictedDarkChem Lite v0.1.0 [M-H]- 168.5848 predictedDeepCCS 1.0 (2019) [M+H]+ 185.3479415 predictedDarkChem Lite v0.1.0 [M+H]+ 170.9428 predictedDeepCCS 1.0 (2019) [M+Na]+ 185.2129415 predictedDarkChem Lite v0.1.0 [M+Na]+ 177.03593 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inducer
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Vincent M: Tesmilifene may enhance breast cancer chemotherapy by killing a clone of aggressive, multi-drug resistant cells through its action on the p-glycoprotein pump. Med Hypotheses. 2006;66(4):715-31. Epub 2006 Jan 18. [Article]
- Brandes LJ, Queen GM, LaBella FS: N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine (DPPE) a chemopotentiating and cytoprotective agent in clinical trials: interaction with histamine at cytochrome P450 3A4 and other isozymes that metabolize antineoplastic drugs. Cancer Chemother Pharmacol. 2000;45(4):298-304. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Histamine receptor activity
- Specific Function
- In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
- Gene Name
- HRH1
- Uniprot ID
- P35367
- Uniprot Name
- Histamine H1 receptor
- Molecular Weight
- 55783.61 Da
References
- Brandes LJ, Bogdanovic RP, Cawker MD, LaBella FS: Histamine and growth: interaction of antiestrogen binding site ligands with a novel histamine site that may be associated with calcium channels. Cancer Res. 1987 Aug 1;47(15):4025-31. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Brandes LJ, Queen GM, LaBella FS: N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine (DPPE) a chemopotentiating and cytoprotective agent in clinical trials: interaction with histamine at cytochrome P450 3A4 and other isozymes that metabolize antineoplastic drugs. Cancer Chemother Pharmacol. 2000;45(4):298-304. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Brandes LJ, Queen GM, LaBella FS: N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine (DPPE) a chemopotentiating and cytoprotective agent in clinical trials: interaction with histamine at cytochrome P450 3A4 and other isozymes that metabolize antineoplastic drugs. Cancer Chemother Pharmacol. 2000;45(4):298-304. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d 24-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- Brandes LJ, Queen GM, LaBella FS: N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine (DPPE) a chemopotentiating and cytoprotective agent in clinical trials: interaction with histamine at cytochrome P450 3A4 and other isozymes that metabolize antineoplastic drugs. Cancer Chemother Pharmacol. 2000;45(4):298-304. [Article]
Drug created at October 21, 2007 22:23 / Updated at February 21, 2021 18:51