Related Experiment Video

Updated: Mar 28, 2026

Identifying Protein-protein Interaction Sites Using Peptide Arrays
07:44

Identifying Protein-protein Interaction Sites Using Peptide Arrays

Published on: November 18, 2014

18.7K

Small-Molecule and Peptide Inhibitors of the Pro-Survival Protein Mcl-1

Andrew M Beekman1, Lesley A Howell2

  • 1School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, Norfolk, NR4 7TJ, UK.

Chemmedchem
|December 24, 2015
PubMed

Insights

Targeting Mcl-1, a key protein in cancer cell survival and therapy resistance, is crucial. This review highlights progress in developing Mcl-1 inhibitors using peptides and small molecules.

Area of Science:

  • Molecular Biology
  • Oncology
  • Drug Discovery

Background:

  • Protein-protein interactions regulate vital cellular processes, making them key drug targets.
  • The Bcl-2 protein family controls intrinsic cell death, with pro-survival members like Mcl-1 often overexpressed in cancers.
  • Mcl-1 overexpression drives resistance to radio- and chemotherapy, necessitating targeted inhibition.

Purpose of the Study:

  • To review current strategies for modulating Mcl-1 activity.
  • To highlight advancements in developing Mcl-1 inhibitors, including stapled peptides and small molecules.
  • To discuss the role of Mcl-1 in cancer therapy resistance.

Main Methods:

  • Review of scientific literature on Mcl-1 modulation.
  • Analysis of progress in peptide-based drug development.
  • Examination of experimental and computational techniques for small molecule discovery.

Main Results:

  • Several Bcl-2 family modulators are in clinical trials, but Mcl-1 specific inhibitors are lacking in clinical application.
  • Mcl-1 inhibition is a significant focus due to its role in cancer progression and therapeutic resistance.
  • Progress has been made in developing both stapled peptides and small molecules targeting Mcl-1.

Conclusions:

  • Targeting Mcl-1 is critical for overcoming cancer therapy resistance.
  • Both stapled peptides and small molecules show promise as Mcl-1 inhibitors.
  • Continued research in Mcl-1 modulation is essential for clinical advancement.
Keywords:
Bcl-2Mcl-1protein-protein interactionssmall-molecule inhibitorsstapled peptides

More Related Videos

Peptide-based Identification of Functional Motifs and their Binding Partners14:28

Peptide-based Identification of Functional Motifs and their Binding Partners

Published on: June 30, 2013

13.1K
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

8.1K

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.2K
Abnormal Proliferation02:23

Abnormal Proliferation

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...
5.4K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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...
9.1K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.9K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.9K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.3K