HZ-A-005, a potent, selective, and covalent Bruton’s tyrosine kinase inhibitor in preclinical development

Huang, Wenhai; Wang, Shu; Zhang, Zhimin; Zhang, Chixiao; Zeng, Shenxin; Liang, Meihao; Shen, Zhengrong

doi:10.1016/j.bioorg.2020.104377

Cited by 5 publications

(3 citation statements)

References 15 publications

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“…HZ‐A‐005 ( 38 ) as a potent ATP‐competitive inhibitor (IC 50 : 2.5 nM) of recombinant human BTK kinase displayed pronounced antiproliferative activity (IC 50 : 10–560 nM, MTT assay) against LY‐10, DOHH‐2, REC‐1, and Mino lymphoma cell lines. [ 52 ] In the Mino xenografted mice model, HZ‐A‐005 (TGI: ~60% at a dose of 12.5 mg/kg through oral administration) was comparable to ibrutinib (TGI: ~65%) at the same condition, whereas HZ‐A‐005 (30 mg/kg, oral administration) reduced ~35% tumor growth in the SU‐DHL‐6 xenografted mice model. No significant loss of body weight was observed in both models, and HZ‐A‐005 did not cause death or significantly alter the body weight even at a dose of 450 mg/kg/day in the healthy mice model, revealing its good safety profile.…”

Section: Pyrazolo[34‐d]pyrimidine/pyrazolo[15‐a]pyrimidine Derivativesmentioning

confidence: 99%

Current scenario of fused pyrimidines with in vivo anticancer therapeutic potential

Xu,

Wang,

2024

Archiv der Pharmazie

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Cancer, characterized by uncontrolled cell growth and metastasis, is responsible for nearly one in six deaths and represents a severe threat to public health worldwide. Chemotherapy can substantially improve the quality of life and survival of patients with cancer, but anticancer chemotherapeutics are associated with a range of adverse effects. Moreover, almost all currently available anticancer chemotherapeutics could develop drug resistance over a period of time of application in cancer patients and ultimately lead to cancer relapse and death in 90% of patients, creating an urgent need to develop new anticancer agents. Fused pyrimidines trait the inextricable part of DNA and RNA and are vital in numerous biological processes. Fused pyrimidines can act on various biological cancer targets and have the potential to address drug resistance. In addition, more than 20 fused pyrimidines have already been approved for clinical treatment of different cancers and occupy a prominent place in the current therapeutic arsenal, revealing that fused pyrimidines are privileged scaffolds for the development of novel anticancer chemotherapeutics. The purpose of this review is to summarize the current scenario of fused pyrimidines with in vivo anticancer therapeutic potential along with their acute toxicity, metabolic profiles as well as pharmacokinetic properties, toxicity and mechanisms of action developed from 2020 to the present to facilitate further rational exploitation of more effective candidates.

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Section: Pyrazolo[34‐d]pyrimidine/pyrazolo[15‐a]pyrimidine Derivativesmentioning

confidence: 99%

Current scenario of fused pyrimidines with in vivo anticancer therapeutic potential

Xu,

Wang,

2024

Archiv der Pharmazie

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“…Huang et al showed another analog with a chlorine atom attached to the acrylamide head of Ibrutinib [ 100 ]. The proposed compound ( 35 ) had high activity against recombinant human BTK kinase with an IC 50 = 2.5 nM.…”

Section: Novel Agent With the Terminal Phenoxy Group From The Most Re...mentioning

confidence: 99%

“…The proposed compound ( 35 ) had high activity against recombinant human BTK kinase with an IC 50 = 2.5 nM. Furthermore, it also exhibited potent inhibitory activity against LY-10, DOHH-2, REC-1, and Mino lymphoma cell lines with IC 50 = 0.16 μM, 0.22 μM, 0.01 μM and 0.56 μM, respectively [ 100 ].…”

Section: Novel Agent With the Terminal Phenoxy Group From The Most Re...mentioning

confidence: 99%

Terminal Phenoxy Group as a Privileged Moiety of the Drug Scaffold—A Short Review of Most Recent Studies 2013–2022

Kozyra

Pitucha

2022

IJMS

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The terminal phenoxy group is a moiety of many drugs in use today. Numerous literature reports indicated its crucial importance for biological activity; thus, it is a privileged scaffold in medicinal chemistry. This review focuses on the latest achievements in the field of novel potential agents bearing a terminal phenoxy group in 2013–2022. The article provided information on neurological, anticancer, potential lymphoma agent, anti-HIV, antimicrobial, antiparasitic, analgesic, anti-diabetic as well as larvicidal, cholesterol esterase inhibitors, and antithrombotic or agonistic activities towards the adrenergic receptor. Additionally, for selected agents, the Structure–Activity–Relationship (SAR) is also discussed. Thus, this study may help the readers to better understand the nature of the phenoxy group, which will translate into rational drug design and the development of a more efficient drug. To the best of our knowledge, this is the first review devoted to an in-depth analysis of the various activities of compounds bearing terminal phenoxy moiety.

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Recent research of BTK inhibitors: Methods of structural design, pharmacological activities, manmade derivatives and structure–activity relationship

Wang

Zhang

et al. 2023

Bioorganic Chemistry

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HZ-A-005, a potent, selective, and covalent Bruton’s tyrosine kinase inhibitor in preclinical development

Cited by 5 publications

References 15 publications

Current scenario of fused pyrimidines with in vivo anticancer therapeutic potential

Current scenario of fused pyrimidines with in vivo anticancer therapeutic potential

Terminal Phenoxy Group as a Privileged Moiety of the Drug Scaffold—A Short Review of Most Recent Studies 2013–2022

Recent research of BTK inhibitors: Methods of structural design, pharmacological activities, manmade derivatives and structure–activity relationship

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