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Related Concept Videos

In-vitro Mutagenesis01:16

In-vitro Mutagenesis

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To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
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Loss of Tumor Suppressor Gene Functions01:12

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Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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The Ras Gene02:38

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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.
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Epigenetic Regulation01:37

Epigenetic Regulation

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Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
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Epigenetic Regulation01:46

Epigenetic Regulation

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Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Genome Editing in Mammalian Cell Lines using CRISPR-Cas
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Hitting KRAS When It's Down.

Ronen Gabizon1, Nir London1

  • 1Department of Organic Chemistry, Weizmann Institute of Science, Rehovot 7600001, Israel.

Journal of Medicinal Chemistry
|June 23, 2020
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Summary
This summary is machine-generated.

The development of KRAS G12C inhibitors like MRTX849 offers new hope for cancer patients. This covalent drug strategy successfully targets a key mutation, marking a significant advancement in oncology drug discovery.

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Area of Science:

  • Oncology
  • Medicinal Chemistry
  • Drug Development

Background:

  • KRAS is a prevalent oncogene and a challenging anticancer target.
  • Decades of research sought effective strategies to inhibit KRAS.
  • The KRAS G12C mutation is a key driver in various cancers.

Purpose of the Study:

  • To present the development of MRTX849, a KRAS G12C inhibitor.
  • To highlight the challenges and solutions in creating covalent anticancer drugs.
  • To showcase the optimization of MRTX849 as a clinical candidate.

Main Methods:

  • Development of an irreversible covalent strategy.
  • Targeting the specific KRAS G12C mutation.
  • Utilizing an α-fluoroacrylamide electrophile for drug design.

Main Results:

  • MRTX849 emerged as a promising clinical candidate.
  • Initial patient results for MRTX849 are encouraging.
  • The study details the successful optimization of a covalent inhibitor.

Conclusions:

  • Targeting KRAS G12C with covalent inhibitors is a viable therapeutic strategy.
  • MRTX849 represents a significant advancement in KRAS-targeted cancer therapy.
  • The development of MRTX849 underscores progress in designing effective covalent drugs.