関連する実験動画
Updated: Mar 5, 2026
13:22
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
8.3K
アロステリック阻害剤ABL001は,BCR-ABL1の二重標的化を可能にします
Andrew A Wylie1, Joseph Schoepfer2, Wolfgang Jahnke2
1Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139, USA.
Nature
|March 23, 2017
まとめ
ABL001 (アシミニブ) は慢性骨髄性白血病 (CML) の新しいアロステリック阻害剤です. ABL001とニロチニブを併用した治療は,マウスのCML腫瘍を根絶し,持続的な疾患制御の可能性を示した.
科学分野:
- 腫瘍学
- 分子生物学
- 薬理学について
背景:
- 慢性骨髄性白血病 (CML) は BCR- ABL1 オンコタンパク質によって引き起こされます.
- キナーゼ阻害剤はCMLのアウトカムを改善しましたが,抵抗性は依然として課題です.
- 新薬のメカニズムの理解は CML 治療の進歩に不可欠です
研究 の 目的:
- 新型アロステリックABL1阻害剤であるABL001 (アシミニブ) の特徴
- 臨床前のCMLモデルにおいて,単体およびニロチニブとの併用によるABL001の有効性を調査する.
主な方法:
- ABL001のABL1のミリストイルポケットへの結合の特徴
- 細胞の効能と抵抗性の変異プロフィールの評価
- 単剤療法と併用療法によるCML異種移植腫瘍を患ったマウスの臨床前試験.
主要な成果:
- ABL001はミリストイルポケットに結合し,不活性なABL1構造を誘導する.
- ABL001とニロチニブは異なった抵抗性変異パターンを示しています.
- ABL001とニロチニブを併用した結果,マウスの腫瘍は再発することなく完全に治癒した.
結論:
- ABL001はミリストイルポケットを標的としたCMLの独特の治療法です.
- ABL001とニロチニブを併用した治療は,CMLに対する強力な臨床前効果を示しています.
- この組み合わせは,耐性を克服し,CML患者で持続的な反応を達成するために有望です.
関連する概念動画
02:57Targeted Cancer Therapies
9.0K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
9.0K
02:50Combination Therapies and Personalized Medicine
6.3K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
6.3K
02:34Inhibition of Cdk Activity
6.1K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.1K
01:08Allosteric Regulation
64.0K
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
64.0K