What drugs target RAS?

Approaches to target RAS indirectly

  • SOS inhibitors.
  • SHP2 inhibitors.
  • Synthetic lethal screens.
  • EGFR family therapies.
  • MAPK pathway: RAF inhibitors.
  • MAPK pathway: MEK inhibitors.
  • MAPK pathway: ERK inhibitors.

What activates the RAS pathway?

RAS Signaling Cascade and Regulation. RAS signaling can be activated by a number of cellular receptors including receptor tyrosine kinases (RTKs), G-protein coupled receptors (GPCRs), and integrin family members.

What is the RAS Signalling pathway?

The Ras/Raf/MAPK pathway is probably the best characterized signal transduction pathway in cell biology. The function of this pathway is to transduce signals from the extracellular milieu to the cell nucleus where specific genes are activated for cell growth, division and differentiation.

Is RAS Druggable?

This makes RAS a strong therapeutic target, but despite having been identified as a drug target for over 30 years, only recently have compounds been developed that show promise in pre-clinical trials2. This paucity of agents has been caused by the lack of clearly druggable pockets on the surface of RAS.

Why is it difficult to target RAS?

Activated Ras is an extremely challenging direct drug target due to the inherent difficulties in disrupting the protein:protein interactions that underlie its activation and function.

What order are genes activated in the Ras signal transduction pathway?

Further, this analysis allowed us to order the components in the Ras signaling pathway as it impinges on regulation of prolactin gene transcription as Ras–>Raf kinase–>mitogen-activated protein kinase–>Ets.

How are Ras proteins activated?

Belonging to the GTPases, ras proteins are activated through the binding of GTP by guanine exchange factors (GEFs) and GTPase-activating proteins (GAPs) resulting in transmitting signals in the cells [4].

What does Ras do in the body?

RAS proteins are important for normal development. Active RAS drives the growth, proliferation, and migration of cells. In normal cells RAS receives signals and obeys those signals to rapidly switch between the active (GTP) form and the inactive (GDP form) states.

What is the function of the RAS protein?

Why is RAS considered Undruggable?

Despite their prolificacy, there is a distinct lack of therapies that target these RAS proteins. RAS inhibitors have been investigated in cancer treatment for more than three decades, yet RAS proteins have come to be known as “undruggable” due to their elusive inhibitory potential – that is, until recently.

What is an undruggable target?

Undruggable targets refer to clinically meaningful therapeutic targets that are ‘difficult to drug’ or ‘yet to be drugged’ via traditional approaches.

What is included in the Ras pathway diagram?

The table comprises the name of each human gene in the RAS Pathway diagram, the name of the cognate protein for each gene, and gene aliases (alternative names). The aliases in bold are gene names more commonly used by RAS researchers.

What are the receptors and messengers of Ras?

At the top of the diagram are the receptors and messengers to the three RAS proteins. The RAS proteins in turn signal through six alternative effector families to affect many downstream targets including TP53, RB1, and MTOR. Arrows represent activation signals, dotted “T” lines represent inhibitory signals.

What are the effectors that link Ras with Ral?

He also included RGL, RGL2 and RGL3 with RALGDS as another effector that links RAS with RAL. Additionally, the RALGAPs, RALGAPA1 and RALGAPA2, and PLCE1 are included as RAS effectors.

Are the ralgaps targeted by mTOR?

Additionally, the RALGAPs, RALGAPA1 and RALGAPA2, and PLCE1 are included as RAS effectors. Philippe Roux ( [email protected]) pointed out errors in the pathway as originally drawn: “The pathway should indicate that RPS6KB1 and RPS6KB2 are targets of mTOR (they are the p70 S6Ks).