Related Experiment Video

Updated: Apr 5, 2026

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
09:32

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity

Published on: October 17, 2025

635

Altiratinib Inhibits Tumor Growth, Invasion, Angiogenesis, and Microenvironment-Mediated Drug Resistance via Balanced

Bryan D Smith1, Michael D Kaufman1, Cynthia B Leary1

  • 1Deciphera Pharmaceuticals, Lawrence, Kansas.

Molecular Cancer Therapeutics
|August 20, 2015
PubMed

Insights

Altiratinib is a novel cancer therapeutic designed to target multiple cancer hallmarks. It inhibits key kinases involved in tumor growth, resistance, and metastasis, offering potential for oral administration and brain cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cancer cells develop resistance through various pathways.
  • Targeting multiple kinases simultaneously can overcome resistance mechanisms.
  • MET, TIE2, and VEGFR2 kinases are crucial in tumor initiation, progression, and angiogenesis.

Purpose of the Study:

  • To design and characterize altiratinib, a multi-kinase inhibitor.
  • To evaluate altiratinib's efficacy against tumor initiation, progression, and drug resistance.
  • To assess altiratinib's potential for treating brain cancers due to its blood-brain barrier penetration.

Main Methods:

  • Kinase inhibition profiling of altiratinib against MET, TIE2, and VEGFR2.
  • In vitro and in vivo studies to assess MET inhibition in wild-type and mutated forms.
  • Evaluation of altiratinib's impact on tumor invasion, metastasis, and angiogenesis pathways.

Main Results:

  • Altiratinib demonstrated balanced inhibition of MET, TIE2, and VEGFR2 kinases by inducing type II inactive conformations.
  • Durable inhibition of both wild-type and mutated MET was observed in vitro and in vivo.
  • Altiratinib effectively inhibited HGF, ANG, and VEGF pathways, blocking tumor invasion and metastasis.

Conclusions:

  • Altiratinib is a promising single therapeutic agent targeting multiple cancer hallmarks.
  • Its multi-kinase inhibition profile offers a strategy to overcome tumor resistance and metastasis.
  • Altiratinib's oral bioavailability and blood-brain barrier penetration suggest potential for treating brain malignancies.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

14.8K
A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds13:34

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds

Published on: April 6, 2016

10.8K

Related Concept Videos

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
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
4.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.7K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.4K
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists

Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
564