We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
INTEGRA BIOSCIENCES AG

Download Mobile App




X-ray Study Explains How Takinib Inhibits TNF-alpha

By LabMedica International staff writers
Posted on 29 Aug 2017
Print article
Image: A molecular model of Takinib, a drug-like molecule that modulates the TNF-alpha inflammatory response, which is at the center of a variety of diseases (Photo courtesy of Duke University).
Image: A molecular model of Takinib, a drug-like molecule that modulates the TNF-alpha inflammatory response, which is at the center of a variety of diseases (Photo courtesy of Duke University).
Takinib, a selective TAK1 inhibiting drug, has been shown to broaden the therapeutic efficacy of TNF-alpha (Tumor necrosis factor-alpha) inhibition for treating cancer and autoimmune diseases.

TAK1 (also known as MAP3K7 or mitogen-activated protein kinase kinase kinase 7) is a key mediator between survival and cell death in TNF-alpha-mediated signaling. TNF-alpha is a cytokine that has a wide variety of functions. It can cause cytolysis of certain tumor cell lines and is a potent pyrogen, causing fever by direct action or by stimulation of interleukin-1 secretion. It can stimulate cell proliferation and induce cell differentiation under certain conditions.

Investigators at Duke University (Durham, NC, USA) recently described the compound Takinib, a potent and selective TAK1 inhibitor that induced apoptosis following TNF-alpha stimulation in cell models of rheumatoid arthritis and metastatic breast cancer.

The investigators used X-ray crystallography to demonstrate that Takinib was an inhibitor of autophosphorylated and non-phosphorylated TAK1 that bound within the ATP-binding pocket and inhibited TAK1 by slowing down the rate-limiting step of TAK1 activation.

Overall, the investigators saw Takinib as an attractive starting point for the development of inhibitors that sensitize cells to TNF-alpha-induced cell death, with general implications for cancer and autoimmune disease treatment.

"The delicate balance between survival and death is often disrupted in disease, and this molecule is able to target the process," said senior author Dr. Timothy Haystead, professor of pharmacology and cancer biology at Duke University. "This compound could potentially enhance the positive parts of TNF-alpha by only targeting tumor cells or inflammatory cells."

The study was published in the August 17, 2017, issue of the journal Cell Chemical Biology.

Related Links:
Duke University

Gold Member
Pharmacogenetics Panel
VeriDose Core Panel v2.0
Verification Panels for Assay Development & QC
Seroconversion Panels
New
Cytomegalovirus Test
NovaLisa Cytomegalovirus (CMV) IgG Test
New
Herpes Simplex Virus ELISA
HSV 2 IgG – ELISA

Print article

Channels

Clinical Chemistry

view channel
Image: The GlycoLocate platform uses multi-omics and advanced computational biology algorithms to diagnose early-stage cancers (Photo courtesy of AOA Dx)

AI-Powered Blood Test Accurately Detects Ovarian Cancer

Ovarian cancer ranks as the fifth leading cause of cancer-related deaths in women, largely due to late-stage diagnoses. Although over 90% of women exhibit symptoms in Stage I, only 20% are diagnosed in... Read more

Molecular Diagnostics

view channel
Image: The breakthrough could result in a higher success rate using a simple oral swab test before IVF (Photo courtesy of Shutterstock)

POC Oral Swab Test to Increase Chances of Pregnancy in IVF

Approximately 15% of couples of reproductive age experience involuntary childlessness. A significant reason for this is the growing trend of delaying family planning, a global shift that is expected to... Read more

Immunology

view channel
Image: The cancer stem cell test can accurately choose more effective treatments (Photo courtesy of University of Cincinnati)

Stem Cell Test Predicts Treatment Outcome for Patients with Platinum-Resistant Ovarian Cancer

Epithelial ovarian cancer frequently responds to chemotherapy initially, but eventually, the tumor develops resistance to the therapy, leading to regrowth. This resistance is partially due to the activation... Read more

Technology

view channel
Image: The new algorithms can help predict which patients have undiagnosed cancer (Photo courtesy of Adobe Stock)

Advanced Predictive Algorithms Identify Patients Having Undiagnosed Cancer

Two newly developed advanced predictive algorithms leverage a person’s health conditions and basic blood test results to accurately predict the likelihood of having an undiagnosed cancer, including ch... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.