Related Experiment Video

Updated: Feb 8, 2026

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.6K

Stop fRETting the Target: Next-Generation RET Inhibitors Have Arrived

Wade T Iams1, Christine M Lovly2

  • 1Division of Hematology/Oncology, McGaw Medical Center of Northwestern University, Chicago, Illinois.

Cancer Discovery
|July 4, 2018
PubMed

Insights

BLU-667 is a novel RET inhibitor designed for precision oncology. This targeted therapy maximizes on-target effects while minimizing off-target impacts, showcasing a new era in cancer treatment.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Precision oncology relies on targeted therapies.
  • Next-generation inhibitors aim to improve efficacy and safety.
  • Genotype-driven development is a key strategy.

Purpose of the Study:

  • To introduce BLU-667, a novel RET inhibitor.
  • To highlight its design principles: maximizing on-target and minimizing off-target effects.
  • To demonstrate its role in genotype-driven drug development and multi-histology basket trials.

Main Methods:

  • Development of BLU-667 as a next-generation RET inhibitor.
  • Validation through multi-histology basket trials.
  • Focus on genotype-driven patient selection.

Main Results:

  • BLU-667 effectively targets RET.
  • The inhibitor demonstrates minimized off-target effects.
  • Basket trials validate its efficacy across multiple cancer types.

Conclusions:

  • BLU-667 exemplifies successful genotype-driven precision oncology.
  • This approach, combining targeted inhibitors with basket trials, is a paradigm for future cancer therapy development.

More Related Videos

Efficient iPS Cell Generation from Blood Using Episomes and HDAC Inhibitors08:14

Efficient iPS Cell Generation from Blood Using Episomes and HDAC Inhibitors

Published on: October 28, 2014

13.3K
A Blood-based Test for the Detection of ROS1 and RET Fusion Transcripts from Circulating Ribonucleic Acid Using Digital Polymerase Chain Reaction10:35

A Blood-based Test for the Detection of ROS1 and RET Fusion Transcripts from Circulating Ribonucleic Acid Using Digital Polymerase Chain Reaction

Published on: April 5, 2018

10.8K

Related Concept Videos

Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
686
Antihypertensive Drugs: Direct Renin Inhibitors01:25

Antihypertensive Drugs: Direct Renin Inhibitors

The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
1.5K
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
2.6K
Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors01:28

Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors

Phosphodiesterase 5 (PDE5) inhibitors are potent enzymes that function to hydrolyze cyclic nucleotides to their corresponding 5' monophosphates. Their unique biochemical properties have been applied in treating Pulmonary Arterial Hypertension (PAH).
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
615
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors01:19

Oral Hypoglycemic Agents: α-Glucosidase Inhibitors

α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
583