更新于：2024-11-01

Chk1 x DNA

更新于：2024-11-01

基本信息

关联

项与 Chk1 x DNA 相关的药物

BBI-355

靶点

Chk1 x DNA

作用机制

Chk1抑制剂 [+1]

在研机构

Boundless Bio, Inc.初创企业

原研机构

Boundless Bio, Inc.初创企业

在研适应症

膀胱癌 [+8]

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

项与 Chk1 x DNA 相关的临床试验

NCT05827614 / Recruiting临床1期

An Open-Label, Multicenter, First-in-Human, Dose-Escalation and Dose-Expansion, Phase 1/2 Study of BBI-355 and BBI-355 in Combination with Select Targeted Therapies in Subjects with Locally Advanced or Metastatic Solid Tumors with Oncogene Amplifications

BBI-355 is an oral, potent, selective checkpoint kinase 1 (or CHK1) small molecule inhibitor in development as an ecDNA (extrachromosomal DNA) directed therapy (ecDTx). This is a first-in-human, open-label, 3-part, Phase 1/2 study to determine the safety profile and identify the maximum tolerated dose and recommended Phase 2 dose of BBI-355 administered as a single agent or in combination with select therapies.

开始日期2023-03-24

申办/合作机构

Boundless Bio, Inc.初创企业

100 项与 Chk1 x DNA 相关的临床结果

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100 项与 Chk1 x DNA 相关的转化医学

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0 项与 Chk1 x DNA 相关的专利（医药）

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项与 Chk1 x DNA 相关的文献（医药）

2002-08-01·Molecular and Cellular Biology3区 · 生物学

Involvement of Replicative Polymerases, Tel1p, Mec1p, Cdc13p, and the Ku Complex in Telomere-Telomere Recombination

3区 · 生物学

Article

作者: Lin, Chuan-Chuan ; Tsai, Yun-Luen ; Tseng, Shun-Fu ; Teng, Shu-Chun ; Chang, Shih-Husan

ABSTRACTTelomere maintenance is required for chromosome stability, and telomeres are typically replicated by the action of the reverse transcriptase telomerase. In both tumor and yeast cells that lack telomerase, telomeres are maintained by an alternative recombination mechanism. Genetic studies have led to the identification of DNA polymerases, cell cycle checkpoint proteins, and telomere binding proteins involved in the telomerase pathway. However, how these proteins affect telomere-telomere recombination has not been identified to date. Using an assay to trace the in vivo recombinational products throughout the course of survivor development, we show here that three major replicative polymerases, α, δ, and ε, play roles in telomere-telomere recombination and that each causes different effects and phenotypes when they as well as the telomerase are defective. Polymerase δ appears to be the main activity for telomere extension, since neither type I nor type II survivors arising via telomere-telomere recombination were seen in its absence. The frequency of type I versus type II is altered in the polymerase α and ε mutants relative to the wild type. Each prefers to develop a particular type of survivor. Moreover, type II recombination is mediated by the cell cycle checkpoint proteins Tel1 and Mec1, and telomere-telomere recombination is regulated by telomere binding protein Cdc13 and the Ku complex. Together, our results suggest that coordination between DNA replication machinery, DNA damage signaling, DNA recombination machinery, and the telomere protein-DNA complex allows telomere recombination to repair telomeric ends in the absence of telomerase.

2001-01-01·Cancer and Metastasis Reviews2区 · 医学

Targeting molecular signals in chk1 pathways as a new approach for overcoming drug resistance.

2区 · 医学

Review

作者: Gunnar Hapke ; Ming-Biao Yin ; Youcef M. Rustum

The common clinical problem in the successful treatment of cancer is the resistance of cancer cells to chemotherapeutic drugs. Chemotherapy kills drug-sensitive cells, but leaves behind a higher proportion of drug-resistant cells. The resistance can be due to altered drug accumulation, retention, metabolism and distribution, or to reduced drug-target interaction. More recently, cell cycle progression, DNA mismatch repair (MMR) and cell death have been shown to play an important role in the regulation of cell resistance to anticancer drugs. Chkl regulation pathways, DNA MMR and p73, as well as altered apoptotic cell death involved in the cell resistance toward DNA damaging agents will be reviewed in this article.