Phase I clinical trial to evaluate the safety, tolerability and pharmacokinetics following single or repeated oral administration of BS1801 in healthy adult volunteers

开始日期2021-04-22

申办/合作机构-

100 项与 BS-1801 相关的临床结果

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100 项与 BS-1801 相关的转化医学

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100 项与 BS-1801 相关的专利（医药）

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项与 BS-1801 相关的文献（医药）

2022-11-24·Journal of Biomolecular Structure and Dynamics

Predictive hybrid paradigm for cytotoxic activity of 1,3,4-thiadiazole derivatives as CDK6 inhibitors against human (MCF-7) breast cancer cell line and its structural modifications: rational for novel cancer therapeutics

Article

作者: Iwaloye, Opeyemi ; Oretade, Oluwaseyi Matthew ; Olowosoke, Christopher Busayo ; Umar, Haruna Isiyaku ; Chukwuemeka, Prosper Obed ; Elabiyi, Michael Omoniyi ; Oretade, Oyeyemi Janet

The dysregulation of cyclin-CDK6 interactions has been implicated in human breast cancer, providing a rationale for more therapeutic options. Recently, ATP-competitive inhibitors have been employed for managing breast cancer. These molecules, like most natural CDKs inhibitors, potently bind in the ATP-binding site of CDK6 to regulate trans-activation. Nonetheless, only a few numbers of these molecules are approved to mitigate breast cancer, thus, ensuring that the search for more selective inhibitors continues. In this study, we attempted to establish the selective predictive models for identifying potent CDK6 inhibitors against a human breast cancer cell-line using a dataset of fifty-two 1,3,4-thiadiazole derivatives. The significant eight descriptor hybrid QSAR models generated exhibited encouraging statistical attributes including __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__R2> 0.70, Q²_LOO > 0.70, Q²_LMO > 0.60, __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__Qfn2 > 0.6. Furthermore, the study designed new compounds based on the activity and structural basis for selectivity of compounds for CDK6. While demonstrating good potency and modest selectivity, the compound C16, which showed significantly high activity of 5.5607 µM and binding energy value of -9.0 Kcal/mol, was used as template for compounds design to generate 10 novel series of 1,3,4-thiadiazole analogues containing benzisoselenazolone scaffolds, with significant pharmacological activity and better selectivity for CDK6. By our rationale, four of the designed compounds (C16b, C16h, C16i, and C16j) with activity values of 6.2584 µM, 6.7812 µM, 6.4717 µM, and 6.2666 µM respectively, and binding affinities of -10.0 kcal/mol, -9.9 kcal/mol, -9.9 kcal/mol, and -9.9 kcal/mol respectively, may emerge as therapeutic options for breast cancer treatment after extensive in vitro and in vivo studies.Communicated by Ramaswamy H. Sarma.

2022-04-01·Journal of Pharmaceutical and Biomedical Analysis3区 · 医学

Quantification of the major circulating metabolite of BS1801, an ebselen analog, in human plasma

3区 · 医学

Article

作者: Jiang, Jinfang ; Deng, Guozhen ; Zhong, Dafang ; Tian, Qianqian ; Ma, Jiao ; Zhou, Jialan ; Yin, Hanwei

BS1801 contains two selenium atoms in its structure, which is a specific inhibitor of thioredoxin reductase intended to treat fibrotic interstitial pneumonia (control pulmonary fibrosis) and liver fibrosis. It is currently in phase I clinical trial. However, there was no report about the metabolic transformation and pharmacokinetics of BS1801. In this study, BS1801 metabolites were characterized in the hepatocytes of different species (monkey, dog, mouse, rat, and human) and plasma specimens using the ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC/Q-TOF MS) method. After incubation, BS1801 could not be detected in the hepatocytes of different species and human plasma. Five metabolites were identified based on the characteristic peak clusters of selenium atoms in the mass spectrum, combined with the product ions obtained by MS-MS through collision-induced-dissociation (CID), including M1 (reduction metabolite), M2 (reduction and Se-methylation metabolite), M4 (M2 further oxidized metabolite) and M5 (Se-methylation and Se-glucuronidation conjugation metabolite), of which the amount of M2 was the highest. By comparing the LC-MS information with the synthesized reference substance, the structure of M2 was confirmed. The principal BS1801 metabolic pathways were identified as reduction and Se-methylation in humans. Subsequently, an accurate and fast LC-MS/MS method was established to verify the major metabolite M2 in human plasma. Acetonitrile-induced protein precipitation was employed to extract M2 from human plasma. The metabolite was separated through XDB-C₁₈ (4.6 × 50 mm, 1.8 µm) under isocratic elution with ammonium acetate (5 mM) containing 0.1% formic acid solution (A) and acetonitrile (B) as the mobile phases. A deuterated internal standard for M2 was prepared to overcome the influence of matrix effects during the detection. The bioanalytical method was shown to be precise, specific, accurate, and good linearity over the range of 3.00-3000 ng/mL, and was implemented to assess the pharmacokinetic profiles of M2 in healthy volunteers following a single oral administration of 450 mg BS1801. This is the first-ever study to identify and quantify the major circulating metabolite of ebselen analogs in human plasma.

2019-12-01·Steroids4区 · 医学

Synthesis and antiproliferative evaluation of novel steroid-benzisoselenazolone hybrids

4区 · 医学

Article

作者: Shi, Haixin ; Xiao, Junan ; Gan, Chunfang ; Wei, Meizhen ; Zhan, Junyan ; Pang, Liping ; Huang, Yanmin ; Liu, Zhiping ; Cui, Jianguo

The two different types of steroidal benzisoselenazolone hybrids were synthesized by incorporating benzisoselenazolone scaffold into dehydroepiandrosterone and B-norcholesterol. The antiproliferative activity of the synthesized compounds against some carcinoma cell lines were investigated. The results showed that some of these compounds have better inhibitory activity than abiraterone on the proliferation of tumor cells associated with human growth hormone, and have less cytotoxicity on normal human cells. In particular, the IC₅₀ values of the compound 8a and 8f are 5.4 and 6.5 µmol/L against human ovarian carcinoma (SKOV3) cell line, and possess SI values of 13.9 and 10.5, respectively. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.

100 项与 BS-1801 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
急性压力	临床前	中国	北京大学	-
急性压力	临床前	中国	上海元熙医药科技有限公司初创企业	-
特发性肺纤维化	临床前	中国	上海元熙医药科技有限公司初创企业	-
肝癌	临床前	中国	上海元熙医药科技有限公司初创企业	-
肝癌	临床前	中国	北京大学	-
肝硬化	临床前	中国	北京大学	-
肝硬化	临床前	中国	上海元熙医药科技有限公司初创企业	-