This study is testing if the recommended dose of BTX-A51 is safe and tolerable in participants with liposarcoma.
The name of the study drug used in this research study is:
-BTX-A51 (a type of kinase inhibitor)

开始日期2024-09-01

申办/合作机构

Dana-Farber Cancer Institute, Inc.

NCT06125522 / Recruiting临床1/2期

TACTIVE-U: AN INTERVENTIONAL SAFETY AND EFFICACY PHASE 1B/2, OPEN-LABEL UMBRELLA STUDY TO INVESTIGATE TOLERABILITY, PK, AND ANTITUMOR ACTIVITY OF VEPDEGESTRANT (ARV-471/PF-07850327), AN ORAL PROTEOLYSIS TARGETING CHIMERA, IN COMBINATION WITH OTHER ANTICANCER TREATMENTS IN PARTICIPANTS AGED 18 AND OLDER WITH ER+ ADVANCED OR METASTATIC BREAST CANCER, SUB-STUDY C (ARV-471 IN COMBINATION WITH SAMURACICLIB)

The purpose of this study is to learn about the safety and effects of the study medicine called vepdegestrant. The safety and effects of vepdegestrant will be see when given with other medicines. Vepdegestrant is studied to see if it can be a possible treatment for advanced metastatic breast cancer. This type of cancer would have spread from where it started (breast) to other parts of the body and would be tough to treat.
The study is seeking for participants who have breast cancer that:
* is hard to treat (advanced) and may have spread to other organs (metastatic). is sensitive to hormonal therapy (it is called estrogen receptor positive).
* is no longer responding to treatments taken before starting this study.
This study is divided into separate sub-studies.
For Sub-Study C:
All the participants will receive vepdegestrant and a medicine called samuraciclib.
Vepdegestrant and samuraciclib will be taken once in a day by mouth. The medicines will be taken at home. The experience of people receiving the study medicines will be studied. This will help see if the study medicine is safe and effective.
Participant will continue to take vepdegestrant and samuraciclib until:
* their cancer is no longer responding, or
* side effects become too severe.
They will have visits at the study clinic about every 4 weeks.

开始日期2024-01-10

申办/合作机构

Pfizer Inc.

[+2]

NCT05963984 / Recruiting临床2期

An Open-label, Interventional, Multicenter, Randomized, Phase 2 Study of Fulvestrant With or Without Samuraciclib in Participants With Metastatic or Locally Advanced Hormone Receptor (HR) Positive and Human Epidermal Growth Factor Receptor (HER)2-Negative Breast Cancer (BC)

The purpose of this study is to evaluate the safety and efficacy of samuraciclib in combination with fulvestrant versus fulvestrant alone in adult participants with metastatic or locally advanced Hormone Receptor (HR) positive and Human Epidermal Growth Factor Receptor (HER)2-negative breast cancer.

开始日期2023-12-14

申办/合作机构

Carrick Therapeutics Ltd.初创企业

[+1]

100 项与 CDK7 相关的临床结果

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100 项与 CDK7 相关的转化医学

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0 项与 CDK7 相关的专利（医药）

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870

项与 CDK7 相关的文献（医药）

2024-12-01·CURRENT OPINION IN PHARMACOLOGY

Role of specific CDKs in regulating DNA damage repair responses and replication stress

Review

作者: Garimella, Sireesha V. ; Roy, Rahul ; Garimella, Sireesha V ; Gampa, Siri Chandana

Cyclins along with their catalytic units, Cyclin-dependent kinases (CDKs) regulate the cell cycle transition and transcription; and are essentially known as 'master regulators' in modulating DNA damage response (DDR) and replication stress. In addition to influencing DNA repair and damage signaling, CDKs also play a pivotal role in cell division fidelity and the maintenance of genomic integrity after DNA damage. In this review, we focus on the intricate ways by which specific CDKs mainly CDK7, CDK9, and CDK12/13, regulate the cell cycle progression and transcription and how their modulation can lead to lethal effects on the integrity of the genome. With a better knowledge of how these CDKs control the DDR and replication stress, it is now possible to combine CDK inhibitors with chemotherapeutic drugs that damage DNA in ways that can be applied in clinical settings as successful therapeutic strategies.

2024-10-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of bivalent small molecule degraders of cyclin-dependent kinase 7 (CDK7)

Article

作者: Ji, Wenzhi ; Byun, Woong Sub ; Hinshaw, Stephen M ; Jiang, Zixuan ; He, Zhixiang ; Du, Guangyan ; Yuan, Linjie ; Mills, Caitlin E ; Jiang, Fen ; Zhang, Tinghu ; Lu, Wenchao ; Bradshaw, Gary A ; Jiang, Jie ; Gray, Nathanael S ; Chung, Mirra

Cyclin-dependent kinase 7, along with cyclin H and MAT1, forms the CDK-activating complex (CAK), which directs cell cycle progression via T-loop phosphorylation of cell cycle CDKs. Pharmacological inhibition of CDK7 leads to selective anti-cancer effects in cellular and in vivo models, motivating several ongoing clinical investigations of this target. Current CDK7 inhibitors are either reversible or covalent inhibitors of its catalytic activity. We hypothesized that small molecule targeted protein degradation (TPD) might result in differentiated pharmacology due to the loss of scaffolding functions. Here, we report the design and characterization of a potent CDK7 degrader that is comprised of an ATP-competitive CDK7 binder linked to a CRL2^VHL recruiter. JWZ-5-13 effectively degrades CDK7 in multiple cancer cells and leads to a potent inhibition of cell proliferation. Additionally, compound JWZ-5-13 displayed bioavailability in a pharmacokinetic study conducted in mice. Therefore, JWZ-5-13 is a useful chemical probe to investigate the pharmacological consequences of CDK7 degradation.

2024-09-06·MEDICINE

Insights into the mechanism of Danggui Liuhuang Tang in treating night sweats: A network pharmacology and molecular docking approach.

Article

作者: Gu, Wei ; Huang, Xingran ; Yang, Ruo ; Jin, Shuying ; Li, Hongyang ; Qiu, Jinling

BACKGROUND:

Night sweats can occur independently or in association with a number of medical conditions and can significantly disrupt daily life. This study focuses on the treatment of primary night sweats. Despite the considerable interest in Danggui Liuhuang Tang (DGLHT), an effective traditional Chinese medicine formula, its mechanism of action remains unknown. There is also no existing literature on the subject.

METHODS:

Network pharmacology and molecular docking techniques.

RESULTS:

Network pharmacology techniques were employed to identify 109 active ingredients and 808 potential targets of DGLHT, as well as 2385 targets associated with night sweating diseases. The screening process yielded 375 common targets shared between DGLHT and night sweating. These included the active ingredients baicalein, quercetin, huarangiin, and tetrahydroafrican antipyrine, and the core targets interleukin 6, serine/threonine protein kinase 1, tumor necrosis factor, GAPDH enzyme, and Src protein kinase were identified. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that DGLHT exerts its therapeutic effects primarily by modulating the PI3K-Akt signaling pathway, neuroactive ligand-receptor interactions, lipid metabolism, and atherosclerosis pathways. Molecular docking revealed strong binding activity between the main active ingredients and their potential targets.

CONCLUSION:

The research identifies promising active ingredients and targets related to the effectiveness of DGLHT in controlling night sweats, thus contributing to the further exploration of potential therapeutics for this condition. In addition, the results of this experiment provide a basis for future research into night sweats.