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関連する概念動画

The Ras Gene02:38

The Ras Gene

7.4K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
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Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

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Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
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Abnormal Proliferation02:23

Abnormal Proliferation

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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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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...
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MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
8.9K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

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多価小分子汎RAS阻害剤

Matthew E Welsch1, Anna Kaplan2, Jennifer M Chambers2

  • 1Department of Chemistry, Columbia University, New York, NY 10027, USA.

Cell
|February 25, 2017
PubMed
まとめ
この要約は機械生成です。

研究者はRASタンパク質を標的にする新しい小分子を開発し,臨床前モデルで抗腫瘍活性を示しました. このパン-RAS阻害剤は新しいがん治療戦略として潜在性を示しています.

キーワード:
GTPーゼについてハラスクラスNRA についてラス癌について化学生物学ドラッグデザインマルチバレンツ小分子

さらに関連する動画

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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関連する実験動画

Last Updated: Mar 7, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

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A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

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科学分野:

  • 薬剤化学
  • 腫瘍学
  • 分子生物学

背景:

  • タンパク質とタンパク質の相互作用 (PPI) は細胞シグナル伝達において極めて重要であり,その障害は治療の可能性を秘めています.
  • RASタンパク質は 細胞成長の重要なレギュレータであり その腫瘍発生性突然変異が 多くの癌を誘発します
  • 小分子によるRASエフェクタ相互作用をターゲットにすることは,がん治療の有望な戦略です.

研究 の 目的:

  • 腫瘍性RASタンパク質を標的とした新しい小分子を設計し合成する.
  • これらのパン-RASリガンドの結合親和性と細胞効果を評価する.
  • 臨床前がんモデルにおける鉛化合物の治療の可能性を評価する.

主な方法:

  • 腫瘍性KRASの隣接する部位を標的とする小分子による構造設計.
  • パン-RASリガンドの合成と特徴付け
  • マイクロスケールの熱泳,NMR,ITCを用いた化合物の結合の生体物理的検証.
  • 細胞死亡率と代謝安定性の評価
  • 異種移植のマウスモデルにおける抗腫瘍活性評価

主要な成果:

  • 1つの化合物である3144は,複数の生体物理的手法によってRASタンパク質に結合することを実証した.
  • 化合物3144は,RAS依存性の癌細胞における致死性を誘発した.
  • この化合物は肝臓の微小体において代謝安定性を示した.
  • 異種移植マウスのがんモデルでは,有意な抗腫瘍作用が観察されました.

結論:

  • パン-RAS抑制は,ある種の癌に対する有効な治療戦略です.
  • 構造ベースのアプローチを使用して設計された多価抑制剤は,タンパク質の表面を効果的に標的にすることができます.
  • RASタンパク質を標的とする小さな分子は 将来の癌治療に 期待されています