Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Antiepileptic Drugs: Potassium Channel Activators

Antiepileptic Drugs: Potassium Channel Activators

Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
Ezogabine has gained approval as an adjunctive treatment...

Antiepileptic Drugs: GABAergic Pathway Potentiators

Antiepileptic Drugs: GABAergic Pathway Potentiators

γ-aminobutyric acid or GABA, plays a pivotal role as an inhibitory neurotransmitter in the brain. GABA pathway potentiators, also known as GABAergic drugs, are a class of pharmaceutical agents designed to enhance the functioning of the GABAergic system. These medications primarily treat epilepsy, a neurological disorder characterized by recurrent seizures.
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for their...

Pharmacovigilance

Pharmacovigilance

Post-marketing surveillance is a critical component of pharmaceutical regulation, often uncovering unanticipated adverse drug reactions (ADRs) once a drug is widely used over an extended period.
This process, termed pharmacovigilance, aims to detect, evaluate, and minimize harmful effects related to medication use. The data collection for pharmacovigilance depends on spontaneous reporting systems, where healthcare professionals or patients voluntarily report suspected ADRs.
In some cases, there...

Drug Discovery: Overview

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...

Treatment Resistent Cancers

Treatment Resistent Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy. SP binds and activates these...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Synthesis and biological evaluation of biaryl alkyl ethers as inhibitors of IDO1.

Bioorganic & medicinal chemistry letters·2023

Same author

Discovery and Preclinical Pharmacology of an Oral Bromodomain and Extra-Terminal (BET) Inhibitor Using Scaffold-Hopping and Structure-Guided Drug Design.

Journal of medicinal chemistry·2021

Same author

Conformational-Analysis-Guided Discovery of 2,3-Disubstituted Pyridine IDO1 Inhibitors.

ACS medicinal chemistry letters·2021

Same author

Discovery of Imidazopyridines as Potent Inhibitors of Indoleamine 2,3-Dioxygenase 1 for Cancer Immunotherapy.

ACS medicinal chemistry letters·2021

Same author

Discovery and Preclinical Evaluation of BMS-986242, a Potent, Selective Inhibitor of Indoleamine-2,3-dioxygenase 1.

ACS medicinal chemistry letters·2021

Same author

Enhanced antitumor immunity by a novel small molecule HPK1 inhibitor.

Journal for immunotherapy of cancer·2021

Search research articles

Related Experiment Video

Updated: Jun 26, 2026

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Published on: December 1, 2020

Discovery of ixabepilone.

¹Oncology Drug Discovery, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, USA. john.hunt@bms.com

Molecular Cancer Therapeutics

|January 29, 2009

Summary

Researchers developed ixabepilone, a novel microtubule-stabilizing agent, to overcome paclitaxel resistance in cancer treatment. This next-generation therapy shows efficacy against resistant tumors, offering new hope for patients with advanced breast cancer.

Area of Science:

Oncology
Pharmacology
Molecular Biology

Background:

Paclitaxel, a microtubule-stabilizing agent, revolutionized cancer treatment but faces limitations due to acquired drug resistance.
Taxane resistance in tumors often arises from P-glycoprotein overexpression or tubulin mutations.
There is a critical need for next-generation antineoplastic agents effective against resistant cancer types.

Observation:

Epothilones, isolated from Sorangium cellulosum, were evaluated for their anticancer potential.
Epothilones A and B demonstrated potent microtubule-stabilizing activity, inducing cell cycle arrest and apoptosis.
These epothilones exhibited cytotoxicity against both paclitaxel-sensitive and resistant cancer cell lines.

Findings:

Semisynthetic modification of epothilones addressed their metabolic instability caused by esterase cleavage.

More Related Videos

Using Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells for Drug Discovery

Using Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells for Drug Discovery

Published on: May 19, 2018

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3

Published on: April 7, 2023

Related Experiment Videos

Last Updated: Jun 26, 2026

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Published on: December 1, 2020

Using Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells for Drug Discovery

Using Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells for Drug Discovery

Published on: May 19, 2018

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3

Published on: April 7, 2023

BMS-247550 (ixabepilone), a lactam analogue of epothilone B, exhibited enhanced metabolic stability and potent tubulin polymerization.

Ixabepilone retained significant activity against paclitaxel-resistant cell lines, including those with P-glycoprotein or mutant tubulin.

Implications:

Ixabepilone represents a successful next-generation microtubule-stabilizing agent designed to overcome taxane resistance.
The approval of ixabepilone for drug-resistant metastatic breast cancer highlights its clinical significance.
This work underscores the potential of targeting microtubules with novel agents for challenging cancer indications.