BIT-225(BIT-225) - 药物靶点：Ion channels_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

Ion channels

作用机制

Ion channels 拮抗剂(离子通道拮抗剂)

治疗领域

免疫系统疾病感染消化系统疾病+ [1]

在研适应症-

非在研适应症

丙型肝炎HIV感染

原研机构

Biotron Ltd.

在研机构-

非在研机构

Biotron Ltd.

最高研发阶段无进展临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C16H15N5O

InChIKeyWVROWPPEIMRGAB-UHFFFAOYSA-N

CAS号917909-71-8

关联

9

项与 BIT-225 相关的临床试验

ACTRN12623000035628 / Not yet recruiting临床2期

A Phase 2, Double Blind Placebo-Controlled Study of BIT225, an Orally Administered SARS-CoV-2 Viroporin Inhibitor, to Evaluate Antiviral Activity, Safety, and Immune Biomarkers in Non-Hospitalised Vaccinated and Unvaccinated Adults with COVID-19.

开始日期2023-05-08

申办/合作机构

Biotron Ltd.

ACTRN12621001354875 / Completed临床2期

A Phase 2 Study of BIT225, an HIV-1 Vpu Inhibitor, in HIV-1 Infected, Treatment Experienced Individuals, Attaining Only Partial Immune Reconstitution on a Durable, Suppressive Combination Antiretroviral Therapy (cART) Regimen: An Open-Label Exploratory Evaluation of Changes in Inflammatory, Immune, Immune Activation and Viral Markers.

开始日期2022-01-10

申办/合作机构

Biotron Ltd.

ACTRN12621000937819 / Active, not recruiting临床2期

A Phase 2 Study of BIT225, a Human Immunodeficiency Virus-1 (HIV-1) Vpu Inhibitor, in Treatment Naive HIV-1 Infected Individuals Commencing Dolutegravir-based Combination Antiretroviral Therapy (cART): Evaluation of Safety, Efficacy and Inflammatory and Immune Activation Markers.

开始日期2021-11-16

申办/合作机构

Biotron Ltd.

100 项与 BIT-225 相关的临床结果

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100 项与 BIT-225 相关的转化医学

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100 项与 BIT-225 相关的专利（医药）

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15

项与 BIT-225 相关的文献（医药）

2024-09-01·Bioorganic & Medicinal Chemistry

Current status of the small molecule anti-HIV drugs in the pipeline or recently approved

Review

作者: Habarurema, Gratien ; Twizeyimana, Eric ; Gahamanyi, Noël ; Claude Tomani, Jean ; Ishimwe, Nestor ; Olawode, Emmanuel Oladayo ; Uyisenga, Jeanne Primitive ; Katandula, Jonathan ; Umumararungu, Théoneste ; Saeed, Shamsaldeen Ibrahim ; Nyandwi, Jean Baptiste ; Mpenda, Matabishi

Human Immunodeficiency Virus (HIV) is the causative agent of Acquired Immunodeficiency Syndrome (AIDS) with high morbidity and mortality rates. Treatment of AIDS/HIV is being complicated by increasing resistance to currently used antiretroviral (ARV) drugs, mainly in low- and middle-income countries (LMICs) due to drug misuse, poor drug supply and poor treatment monitoring. However, progress has been made in the development of new ARV drugs, targeting different HIV components (Fig. 1). This review aims at presenting and discussing the progress made towards the discovery of new ARVs that are at different stages of clinical trials as of July 2024. For each compound, the mechanism of action, target biomolecule, genes associated with resistance, efficacy and safety, class, and phase of clinical trial are discussed. These compounds include analogues of nucleoside reverse transcriptase inhibitors (NRTIs) - islatravir and censavudine; non-nucleoside reverse transcriptase inhibitors (NNRTIs) - Rilpivirine, elsulfavirine and doravirine; integrase inhibitors namely cabotegravir and dolutegravir and chemokine coreceptors 5 and 2 (CC5/CCR2) antagonists for example cenicriviroc. Also, fostemsavir is being developed as an attachment inhibitor while lenacapavir, VH4004280 and VH4011499 are capsid inhibitors. Others are maturation inhibitors such as GSK-254, GSK3532795, GSK3739937, GSK2838232, and other compounds labelled as miscellaneous (do not belong to the classical groups of anti-HIV drugs or to the newer classes) such as obefazimod and BIT225. There is a considerable progress in the development of new anti-HIV drugs and the effort will continue since HIV infections has no cure or vaccine till now. Efforts are needed to reduce the toxicity of available drugs or discover new drugs with new classes which can delay the development of resistance.

2023-08-01·PLoS pathogens

Post-infection treatment with the E protein inhibitor BIT225 reduces disease severity and increases survival of K18-hACE2 transgenic mice infected with a lethal dose of SARS-CoV-2.

Article

作者: Rosenkilde, Mette M ; Miller, Michelle ; Bobardt, Michael ; Thomson, Audrey ; Bentzen, Bo Hjorth ; Klumpp, Klaus ; Becker, Stephen ; Yan, Yannan ; Gallay, Philippe ; Ewart, Gary

The Coronavirus envelope (E) protein is a small structural protein with ion channel activity that plays an important role in virus assembly, budding, immunopathogenesis and disease severity. The viroporin E is also located in Golgi and ER membranes of infected cells and is associated with inflammasome activation and immune dysregulation. Here we evaluated in vitro antiviral activity, mechanism of action and in vivo efficacy of BIT225 for the treatment of SARS-CoV-2 infection. BIT225 showed broad-spectrum direct-acting antiviral activity against SARS-CoV-2 in Calu3 and Vero cells with similar potency across 6 different virus strains. BIT225 inhibited ion channel activity of E protein but did not inhibit endogenous currents or calcium-induced ion channel activity of TMEM16A in Xenopus oocytes. BIT225 administered by oral gavage for 12 days starting 12 hours before infection completely prevented body weight loss and mortality in SARS-CoV-2 infected K18 mice (100% survival, n = 12), while all vehicle-dosed animals reached a mortality endpoint by Day 9 across two studies (n = 12). When treatment started at 24 hours after infection, body weight loss, and mortality were also prevented (100% survival, n = 5), while 4 of 5 mice maintained and increased body weight and survived when treatment started 48 hours after infection. Treatment efficacy was dependent on BIT225 dose and was associated with significant reductions in lung viral load (3.5 log10), virus titer (4000 pfu/ml) and lung and serum cytokine levels. These results validate viroporin E as a viable antiviral target and support the clinical study of BIT225 for treatment and prophylaxis of SARS-CoV-2 infection.

2021-06-04·The Journal of Infectious Diseases

Human Immunodeficiency Virus Type 1 Vpu Inhibitor, BIT225, in Combination with 3-Drug Antiretroviral Therapy: Inflammation and Immune Cell Modulation

Article

作者: Avihingsanon, Anchalee ; Murphy, Robert L ; Luscombe, Carolyn A ; Han, Win Min ; Gatechompol, Sivaporn ; Becker, Stephen ; Miller, Michelle ; Supparatpinyo, Khuanchai ; Ewart, Gary D ; Thomson, Audrey S

AbstractBIT225 is a first-in-class inhibitor of human immunodeficiency virus (HIV) type 1 Vpu. A phase II trial enrolled 36 HIV-1–infected, treatment-naive participants in Thailand to receive standard-of-care antiretroviral therapy (ART), tenofovir disoproxil fumarate/emtricitabine/efavirenz (Atripla), with 100 or 200 mg of BIT225 or placebo (daily) for 12 weeks. Combined treatment with BIT225 and ART was found to be generally safe and well tolerated, with antiviral efficacy comparable to that of ART alone. The secondary end point—soluble CD163, a marker of monocyte/macrophage inflammation—was noted to be significantly decreased in the BIT225 arm. Plasma-derived activated CD4+ and CD8+ T cells, natural killer cells, and interleukin 21 were increased in those treated with BIT225. These findings are consistent with inhibition of the known effects of HIV Vpu and may reflect clinically important modulation of inflammatory and immune function. Further clinical study is planned to both confirm and extend these important findings in treatment-naive, and treatment-experienced individuals.Clinical Trials Registration. Australian New Zealand Clinical Trials Registry (Universal Trial Number U1111-1191-2194).

100 项与 BIT-225 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	BIT-225	-	-

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
HIV感染	临床2期	泰国	Biotron Ltd.	2012-10-20
丙型肝炎	临床2期	泰国	Biotron Ltd.	2010-09-28

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


IAS2014	N/A	-	21	BIT225 400 mg BID	網壓製襯膚蓋憲構鹹積(鑰夢蓋餘憲壓窪醖齋餘) = 製簾遞選襯糧膚觸簾廠膚顧糧製壓觸蓋鏇蓋艱 (獵糧廠齋築積願構鏇醖 )	-	2014-01-01