A Phase I/II, Open-Label Study of the Safety, Tolerance, Pharmacokinetics, Drug-Interaction and Anti-HIV Activity of Intramuscularly Administered Alpha-Epi-Br (HE2000) in HIV-Infected Patients on Salvage Therapy

The purpose of this study is to see if it is safe and effective to give HE2000, an experimental anti-HIV drug, to HIV-infected patients on salvage therapy (emergency treatment used when a patient has not responded to standard therapy).
HE2000 is a hormone that is suspected to make it more difficult for HIV to live in cells.

开始日期-

申办/合作机构

Harbor Therapeutics, Inc.

100 项与 Immunitin 相关的临床结果

登录后查看更多信息

100 项与 Immunitin 相关的转化医学

登录后查看更多信息

100 项与 Immunitin 相关的专利（医药）

登录后查看更多信息

项与 Immunitin 相关的文献（医药）

2021-07-12·Clinical and Experimental Immunology3区 · 医学

16α-Bromoepiandrosterone as a new candidate for experimental diabetes–tuberculosis co-morbidity treatment

3区 · 医学

Article

作者: Ramos-Espinosa, Octavio ; Bini, Estela ; Mata-Espinosa, Dulce ; Baay-Guzman, Guillermina ; Torres, Nimbe ; Hernández-Pando, Rogelio ; Chamberlin, William ; Tovar, Armando ; Ge, Yu ; Marquina-Castillo, Brenda ; Yepez, Sara Huerta ; Torre-Villalvazo, Ivan ; López-Torres, Manuel Othoniel ; Carranza, Andrea ; Barrios-Payan, Jorge A

SummaryTuberculosis (TB) is the leading cause of death from a single bacterial infectious agent and is one of the most relevant issues of public health. Another pandemic disease is type II diabetes mellitus (T2D) that is estimated to affect half a billion people in the world. T2D is directly associated with obesity and a sedentary lifestyle and is frequently associated with immunosuppression. Immune dysfunction induced by hyperglycemia increases infection frequency and severity. Thus, in developing countries the T2D/TB co-morbidity is frequent and represents one of the most significant challenges for the health-care systems. Several immunoendocrine abnormalities are occurring during the chronic phase of both diseases, such as high extra-adrenal production of active glucocorticoids (GCs) by the activity of 11-β-hydroxysteroid dehydrogenase type 1 (11-βHSD1). 11-βHSD1 catalyzes the conversion of inactive cortisone to active cortisol or corticosterone in lungs and liver, while 11-β-hydroxysteroid dehydrogenase type 2 (11-βHSD2) has the opposite effect. Active GCs have been related to insulin resistance and suppression of Th1 responses, which are deleterious factors in both T2D and TB. The anabolic adrenal hormone dehydroepiandrosterone (DHEA) exerts antagonistic effects on GC signaling in immune cells and metabolic tissues; however, its anabolic effects prohibit its use to treat immunoendocrine diseases. 16α-bromoepiandrosterone (BEA) is a water miscible synthetic sterol related to DHEA that lacks an anabolic effect while amplifying the immune and metabolic properties with important potential therapeutic uses. In this work, we compared the expression of 11-βHSD1 and the therapeutic efficacy of BEA in diabetic mice infected with tuberculosis (TB) (T2D/TB) with respect to non-diabetic TB-infected mice (TB). T2D was induced by feeding mice with a high-fat diet and administering a single low-dose of streptozotocin. After 4 weeks of T2D establishment, mice were infected intratracheally with a high-dose of Mycobacterium tuberculosis strain H37Rv. Then, mice were treated with BEA three times a week by subcutaneous and intratracheal routes. Infection with TB increased the expression of 11-βHSD1 and corticosterone in the lungs and liver of both T2D/TB and TB mice; however, T2D/TB mice developed a more severe lung disease than TB mice. In comparison with untreated animals, BEA decreased GC and 11-βHSD1 expression while increasing 11-βHSD2 expression. These molecular effects of BEA were associated with a reduction in hyperglycemia and liver steatosis, lower lung bacillary loads and pneumonia. These results uphold BEA as a promising effective therapy for the T2D/TB co-morbidity.

2010-08-01·Microbes and Infection3区 · 医学

Parasiticidal effect of 16α-bromoepiandrosterone (EpiBr) in amoebiasis and cysticercosis

3区 · 医学

Article

作者: Claudia Cervantes-Rebolledo ; Jorge Morales-Montor ; Charles Dowding ; Julio César Carrero ; Chris Reading ; Romel Hernández-Bello ; James Frincke ; José Antonio Vargas-Villavicencio

The effect of the dehydroepiandrosterone analog 16alpha-bromoepiandrosterone (EpiBr) was tested on the tapeworm Taenia crassiceps and the protist Entamoeba histolytica, both in vivo and in vitro. Administration of EpiBr prior to infection with cysticerci in mice reduced the parasite load by 50% compared with controls. EpiBr treatment induced 20% reduction on the development of amoebic liver abscesses in hamsters. In vitro treatment of T. crassiceps and E. histolytica cultures with EpiBr, reduced reproduction, motility and viability in a dose- and time-dependent fashion. These results leave open the possibility of assessing the potential of this hormonal analog as a possible anti-parasite drug, including cysticercosis and amoebiasis.

2010-07-01·Bioorganic & Medicinal Chemistry3区 · 医学

16-Bromoepiandrosterone, an activator of the mammalian immune system, inhibits glucose 6-phosphate dehydrogenase from Trypanosoma cruzi and is toxic to these parasites grown in culture

3区 · 医学

Article

作者: Otavio Henrique Thiemann ; Artur T. Cordeiro

Glucose 6-phosphate dehydrogenase (G6PDH) catalyzes the first step of the pentose-phosphate pathway which supplies cells with ribose 5-phosphate (R5P) and NADPH. R5P is the precursor for the biosynthesis of nucleotides while NADPH is the cofactor of several dehydrogenases acting in a broad range of biosynthetic processes and in the maintenance of the cellular redox state. RNA interference-mediated reduction of G6PDH levels in bloodstream-form Trypanosoma brucei validated this enzyme as a drug target against Human African Trypanosomiasis. Dehydroepiandrosterone (DHEA), a human steroidal pro-hormone and its derivative 16α-bromoepiandrosterone (16BrEA) are uncompetitive inhibitors of mammalian G6PDH. Such steroids are also known to enhance the immune response in a broad range of animal infection models. It is noteworthy that the administration of DHEA to rats infected by Trypanosoma cruzi, the causative agent of Human American Trypanosomiasis (also known as Chagas' disease), reduces blood parasite levels at both acute and chronic infection stages. In the present work, we investigated the in vitro effect of DHEA derivatives on the proliferation of T. cruzi epimastigotes and their inhibitory effect on a recombinant form of the parasite's G6PDH (TcG6PDH). Our results show that DHEA and its derivative epiandrosterone (EA) are uncompetitive inhibitors of TcG6PDH, with K(i) values of 21.5 ± 0.5 and 4.8 ± 0.3 μM, respectively. Results from quantitative inhibition assays indicate 16BrEA as a potent inhibitor of TcG6PDH with an IC₅₀ of 86 ± 8 nM and those from in vitro cell viability assays confirm its toxicity for T. cruzi epimastigotes, with a LD₅₀ of 12 ± 8 μM. In summary, we demonstrated that, in addition to host immune response enhancement, 16BrEA has a direct effect on parasite viability, most likely as a consequence of TcG6PDH inhibition.

100 项与 Immunitin 相关的药物交易

登录后查看更多信息