To perform preliminary clinical testing of diethylhomospermine (DEHSPM), a polyamine analogue, for refractory AIDS-related diarrhea.
Possibly, DEHSPM will reduce stool volume and frequency in patients with refractory AIDS-related diarrhea.

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100 Clinical Results associated with Diethylhomospermine

100 Translational Medicine associated with Diethylhomospermine

100 Patents (Medical) associated with Diethylhomospermine

Literatures (Medical) associated with Diethylhomospermine

01 Apr 2004·Investigational New DrugsQ3 · MEDICINE

Phase I Trial of the Polyamine Analog N1,N14-Diethylhomospermine (DEHSPM) in Patients with Advanced Solid Tumors

Q3 · MEDICINE

Article

Author: Arzoomanian, Rhoda ; Feierabend, Chris ; Wilding, George ; King, David ; Pomplun, Marcia ; Alberti, Dona ; Tutsch, Kendra

BACKGROUNDThis phase I study was conducted to determine maximal tolerated dose (MTD) and dose-limiting toxicities (DLT) in patients with advanced solid tumors treated with the polyamine analog N1, N14-diethylhomospermine (DEHSPM).METHODSPatients were treated with DEHSPM administered as a subcutaneous (SC) injection daily for five consecutive days repeated every 4 weeks. Three dose levels were examined starting at 12.5 mg/m2/day, escalating to 37.5 mg/m2/day.RESULTSA total of 15 patients were enrolled. Dose limiting toxicities (grade 3 or 4) included nausea, vomiting, constipation, ileus, elevations of aspartate aminotransferase (AST) and alkaline phosphatase, hyperbilirubinemia, and ventricular bigeminy.CONCLUSIONDEHSPM given as a SC injection is overall well tolerated at lower doses, but significant toxicities were observed at the 37.5mg/m2/day dose level. MTD was established at 25 mg/m2/day but further investigation with this study drug is not recommended secondary to the potential for neurotoxicities and hepatic damage as a result of cumulative doses.

01 Feb 2001·Journal of Medicinal ChemistryQ1 · MEDICINE

Conformationally Restricted Analogues of ¹N,¹⁴N-Bisethylhomospermine (BE-4-4-4): Synthesis and Growth Inhibitory Effects on Human Prostate Cancer Cells

Q1 · MEDICINE

Article

Author: Reddy, Venodhar K. ; Valasinas, Aldonia ; Basu, Hirak S. ; Marton, Laurence J. ; Sarkar, Aparajita ; Frydman, Benjamin

Twelve analogues of 1N,14N-bisethylhomospermine (BE-4-4-4) with restricted conformations were synthesized in the search for cancer chemotherapeutic agents with higher cytotoxic activities and lower systemic toxicities than BE-4-4-4. The central butane segment of BE-4-4-4 was replaced with a 1,2-substituted cyclopropane ring, a 1,2-substituted cyclobutane ring, and a 2-butene residue. In each case, the cis/trans-isomeric pair was synthesized. Cis-monounsaturation(s) was also introduced at the outer butane segment(s) of BE-4-4-4. The two possible cis-dienes and a cis-triene formally derived from the tetraazaeicosane skeleton of BE-4-4-4 were also prepared. Four cultured human prostate cancer cell lines (LnCap, DU145, DuPro, and PC-3) were treated with the new tetramines to examine their effects on cell growth with a MTT assay. One representative cell line (DuPro) was selected to further study the cellular uptake of the novel tetramines, their effects on intracellular polyamine pools, and their cytotoxicity. All tetramines entered the cells, reduced cellular putrescine and spermidine pools while exerting only a small effect on the spermine pool, inhibited cell growth, and killed 2-3 logs of cells after 6 days of treatment at 10 microM. Four new tetramines, the two cyclopropyl isomers, the trans-cyclobutyl isomer, and the (5Z)-tetraazaeicosene, were more cytotoxic than their saturated counterpart (BE-4-4-4). Their cytotoxicity, however, could not be correlated either with their cellular uptake or with their ability to deplete intracellular polyamine pools. We attribute their cytotoxicity to their specific molecular structures. The cytotoxicity was markedly reduced when the central butane segment was deprived of its rotational freedom by replacing it with a double bond. Introduction of a triple bond or a benzene-1,2-dimethyl residue at the central segment of the polyamine chain, led to complete loss of biological activity. The conformationally restricted alicyclic derivatives were not only more cytotoxic than was the freely rotating BE-4-4-4 by several orders of magnitude but also had much lower systemic toxicities than the latter. Thus, we obtained new tetramines with a wider therapeutic window than BE-4-4-4.

01 Sep 1998·Journal of Medicinal ChemistryQ1 · MEDICINE

Effect of Polyamine Analogues on Hypusine Content in JURKAT T-Cells

Q1 · MEDICINE

Article

Author: Bergeron, Raymond J. ; Zimmerman, Curt O. ; Smith, Richard E. ; Müller, Ralf ; Yao, Hua ; McCosar, Bruce H. ; Weimar, William R.

The availability of synthetic hypusine and deoxyhypusine has made it possible to develop analytical methods which allow for the measurement of these compounds in various tissues. The methods involve dansylation of extracts from the pellet remaining after perchloric acid precipitation of cell or tissue homogenates, followed by high-performance liquid chromatography. To demonstrate the utility of this approach, the impact of four polyamine analogues, N1,N11-diethylnorspermine (DENSPM), N1,N14-diethylhomospermine (DEHSPM), 1,6,12-triazadodecane [(4,5) triamine], and 1,7, 13-triazatridecane [(5,5) triamine], on hypusine levels in a human T-cell line (JURKAT) is evaluated. All four analogues are active in controlling cell growth and compete well with spermidine for the polyamine transport apparatus. After 144 h of exposure to JURKAT cells, DENSPM reduces putrescine to below detectable limits and spermidine to 10% of the level in control cells. The other three analogues diminish both putrescine and spermidine to below detectable limits. The effectiveness with which the compounds lower spermine levels is DENSPM > DEHSPM > (4,5) triamine > (5,5) triamine. The analogues decrease the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase in a similar fashion. Of the four polyamines, DENSPM and DEHSPM are potent at lowering intracellular hypusine levels after 144 h: 59 +/- 9% and 73 +/- 12% of control levels, respectively. The other two analogues have marginal effects.

100 Deals associated with Diethylhomospermine

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Colitis, Ulcerative	Phase 2	US	GelTex Pharmaceuticals, Inc.	-
Diarrhea	Phase 2	US	GelTex Pharmaceuticals, Inc.	-
Diarrhea	Phase 2	-	Genzyme Corp.	-
Gastritis	Phase 2	US	GelTex Pharmaceuticals, Inc.	-
Neoplasms	Phase 2	US	GelTex Pharmaceuticals, Inc.	-

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