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Mutations

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...

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Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction

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Novel Small Molecule, UTS-1401, as a Radioprotector for Total-Body Irradiation.

Frederick A Valeriote¹, Stephen L Brown², Joseph Media¹

¹Department of Internal Medicine, Henry Ford Health, Detroit, Michigan, 48202.

Radiation Research

|May 27, 2024

Summary

A new small molecule, UTS-1401, significantly increased survival rates in mice after total-body irradiation (TBI). This promising radioprotective agent also protected hematopoietic stem cells and bone marrow progenitors.

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Published on: February 17, 2019

Area of Science:

Radioprotection
Radiation Biology
Pharmacology

Background:

Total-body irradiation (TBI) poses significant health risks due to cellular damage.
Development of effective radioprotective agents is crucial for mitigating radiation-induced harm.
Small molecules offer potential for targeted radioprotection.

Purpose of the Study:

To evaluate the radioprotective efficacy of a novel small molecule, UTS-1401, against TBI.
To determine the dose-response relationship and optimal administration of UTS-1401.
To assess the protective effects of UTS-1401 on hematopoietic stem cells and bone marrow progenitors.

Main Methods:

Female and male NIH Swiss mice were pretreated with UTS-1401 before undergoing TBI at various doses (6.5-8.5 Gy).
Survival rates, body weight changes, spleen weight, and hematopoietic stem cell survival (spleen colony assay) were assessed.
Bone marrow colony-forming unit-granulocyte-macrophage (CFU-GM) was evaluated in a separate in vivo study.

Main Results:

UTS-1401 significantly increased survival rates in mice exposed to TBI compared to untreated controls.
The radioprotective effect was dose-dependent in male mice, with 150 mg/kg being optimal at 8.5 Gy TBI.
UTS-1401 protected spleen weight and hematopoietic stem cells (treated/untreated ratio 2.0-3.2) up to 72 hours pre-TBI, and also protected bone marrow CFU-GM.

Conclusions:

UTS-1401 demonstrates significant radioprotective potential against TBI in a whole-animal model.
The agent effectively protects hematopoietic stem cells and bone marrow progenitor cells, indicating broad protective mechanisms.
UTS-1401 is a promising candidate for further development as a radioprotective agent.