TESMILIFENE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H25NO
Molecular Weight	283.4079
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN(CC)CCOC1=CC=C(CC2=CC=CC=C2)C=C1

InChI

InChIKey=NFIXBCVWIPOYCD-UHFFFAOYSA-N

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

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Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14722035 | https://www.ncbi.nlm.nih.gov/pubmed/16217292 | https://www.ncbi.nlm.nih.gov/pubmed/16823511

Tesmilifene is a small-molecule antineoplastic drug and chemopotentiator that was under development by YM BioSciences for the treatment of breast cancer. Tesmilifene was developed as a selective ligand of the antiestrogen binding sites without estrogen receptor affinity. Tesmilifene potentiates the cytotoxicity of a variety of chemotherapy drugs in vitro and in vivo. Tesmilifene in combination with doxorubicin provides an unexpected and very large survival advantage over doxorubicin alone in a randomized trial in phase III clinical trial in advanced breast cancer. Unfortunately, Tesmilifene application associated with high rate disease and treatment-related adverse events and poor quality of life. Based on these results further development of Tesmilifene was discontinued

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H1 receptor 315 Target ID: P35367 Gene ID: 3269.0 Gene Symbol: HRH1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/2886214	Antagonist 2778
Multidrug resistance protein 1 8 Target ID: P08183 Gene ID: 5243.0 Gene Symbol: ABCB1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/16413681	Activator 1430

PubMed

Title	Date	PubMed
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.	1990 May	2374133
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.	2000	10755318
Inhibition of effects of endogenously synthesized histamine disturbs in vitro human dendritic cell differentiation.	2001 Apr 2	11306145
Increased histidine decarboxylase expression during in vitro monocyte maturation; a possible role of endogenously synthesised histamine in monocyte/macrophage differentiation.	2001 Aug	11556524
Different h2 receptor antihistamines dissimilarly retard the growth of xenografted human melanoma cells in immunodeficient mice.	2002	12377215
Murine and human hematopoietic colony formation: a possible regulatory role for intracellular histamine.	2002	12371609
Effect of alpha-FMH and DPPE on colony-forming properties of human peripheral progenitor cells.	2002 Jul	12132991
Cimetidine and a tamoxifen derivate reduce tumour formation in SCID mice xenotransplanted with a human melanoma cell line.	2002 Jun	12140379
N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine increases the permeability of primary mouse cerebral endothelial cell monolayers.	2003 Apr	12755402
Phase III study of N,N-diethyl-2-[4-(phenylmethyl) phenoxy]ethanamine (BMS-217380-01) combined with doxorubicin versus doxorubicin alone in metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group Study MA.19.	2004 Jan 15	14722035
Phase II trial of tesmilifene plus mitoxantrone and prednisone for hormone refractory prostate cancer: high subjective and objective response in patients with symptomatic metastases.	2005 Nov	16217292
Tesmilifene may enhance breast cancer chemotherapy by killing a clone of aggressive, multi-drug resistant cells through its action on the p-glycoprotein pump.	2006	16413681
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.	2006 Dec	16823511
The phospholipidosis-lnducing potential of the chemopotentiating drug, N,N-Diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine (DPPE, tesmilifene) correlates with its stimulation of phosphatidylserine synthesis and exposure on the plasma membrane in MCF-7 breast cancer cells.	2007	18605231
On-demand generation of an efficient catalyst for pyridine formation from unactivated nitriles and alpha,omega-diynes using CoCl2-6H2O, dppe, and Zn.	2007 Mar 1	17261007
N,N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine (DPPE; tesmilifene), a chemopotentiating agent with hormetic effects on DNA synthesis in vitro, may improve survival in patients with metastatic breast cancer.	2008 Feb	18480139
Enhancement of cytotoxicity of natural product drugs against multidrug resistant variant cell lines of human head and neck squamous cell carcinoma and breast carcinoma by tesmilifene.	2009 Feb 18	18986763
Preferential killing of breast tumor initiating cells by N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine/tesmilifene.	2009 Jan 1	19118039
Effects of tesmilifene, a substrate of CYP3A and an inhibitor of P-glycoprotein, on the pharmacokinetics of intravenous and oral docetaxel in rats.	2010 Aug	20663044

Patents

Sample Use Guides

In Vivo Use Guide

5.3 mg/kg Tesmilifene + 20 mg/m^2 Doxorubicin

Route of Administration: Intravenous

Name

Type

Language

TESMILIFENE

Official Name

English

TESMILIFENE [MI]

Common Name

English

tesmilifene [INN]

Common Name

English

Tesmilifene [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C481