What does Undruggable mean?
The term ‘undruggable’ was coined to describe proteins that could not be targeted pharmacologically. However, progress is being made to ‘drug’ many of these targets, and therefore more appropriate terms might be ‘difficult to drug’ or ‘yet to be drugged’.
What does an undruggable target mean?
In the world of drug discovery, “undruggable” targets are like the stubborn children of biology, proteins that are considered too challenging to bind with conventional molecules.
Why is myc an undruggable target?
This cancer-causing protein has been thought to be undruggable because it is a disordered protein, which doesn’t have a fixed structure. This makes it challenging to develop a compound that could target any pocket in the protein, according to Sarki Abdulkadir, MD, PhD.
Why was the RAS protein considered Undruggable by scientists?
But RAS proteins have been considered “undruggable,” in part because their smooth surfaces offer no obvious pockets to target with a drug.
What are oncogenic targets?
When a tumor relies heavily on one mutated gene to keep growing and spreading, this is called oncogenic addiction. Certain therapies target these mutated genes (oncogenes) necessary for tumor growth and aim to stopping the genetic activity of that gene.
How many druggable targets are there?
Drug targets and druggable targets Published estimates of the number of current human drug targets range from 200 to 500. Drews2 estimate 483 target proteins in humans and pathogens. Hopkins and Groom3 identified 399 nonredundant molecular targets in 130 protein families that bind ligands with drug-like properties.
What is the function of MYC?
MYC gene encodes a multifunctional, nuclear phosphoprotein that controls a variety of cellular functions, including cell cycle, cell growth, apoptosis, cellular metabolism and biosynthesis, adhesion, and mitochondrial biogenesis.
Why is Kras Undruggable?
For more than 30 years after its discovery, KRAS was considered undruggable target due to the intrinsic characteristics of KRAS proteins. The KRAS is small and has a considerably smooth and shallow surface, resulting in difficulty of small molecule binding to the KRAS.
What are oncogenic drivers?
Oncogenic driver mutations refer to mutations that are responsible for both the initiation and maintenance of the cancer. These mutations are often found in genes that encode for signaling proteins that are critical for maintaining normal cellular proliferation and survival.
How do you treat oncogenes?
Targeted therapy for oncogenic addiction involves identification of the oncogene specific to a cancer and inhibiting the activity of the proteins it encodes. Most of the targeted therapies for oncogenic addiction are small-molecule inhibitors, which bind to cell proteins and block their activity.
How do you validate target?
Target validation is the first step in discovering a new drug and can typically take 2-6 months. The process involves the application of a range of techniques that aim to demonstrate that drug effects on the target can provide a therapeutic benefit with an acceptable safety window.