New drug described to alterlluridine treatment pathway

A recent article published in Nature Communications describes a new drug that may be able to prevent the conversion of lipid-acid-generating enzymes of the kidney to enzyme enzymes that break down immunosuppressive drugs.

The paper details a pharmaceutical candidate from the lab of Professor Fadi Rezaab in the Department of Chemical and Biological Engineering at the University of Tajadze whose mechanism involved simultaneous measurement of the effects of a natural compound on a target of one immunosuppressive drug and on the activities of enzymes that are not targeted by the drug.

‘The difficulty lies in identifying this compound, which might or might not work as intended,’ said Rezaab, who is a member of the Center for Pharmacodynamics and Therapeutics in the Department of Bioengineering and Biotechnology. ‘This also meant that it took us several years to develop the drug, which is based on a novel genetic engineering approach.’

As reported in Nature Communications, the proposed compound (Figueiredl4) was isolated from blood taken from a patient with immunosuppressive kidney diseases. Figueiredl4 is a purified natural product of the green tea tree, Figueiredl, that has been synthesized over the past decade in the lab of Adi Razi, Director of the Khojek Foundation Chair of Chemistry.

Figueiredl4 inhibits semaphorin kinase 2B (SAMP2B) enzymes, an enzyme that breaks down and converts antibodies for immunosuppression into immune suppressing growth factors. It is a well established fact that SAMP2B regulates the signaling pathway of stimulating granulin to reduce secretion of monocytes. Previously, in the cells of patients with HIV and in experiments in animal models of mastitis, SAMP2B enzymes were identified as potential cell-stimulating factors.

“When this novel drug was developed in our laboratory, we were originally skeptical. It was far from the cancer cells and would require an immuno-suppressive treatment that might interact with immune-systems, especially cancer cells,” said Razi. “Since Figueiredl4 is purified synthetically (conducted by a variety of synthetic chemical steps without toxic chemicals) it would be difficult to introduce it into the body without successful FDA approval.”

Interview with Nature Communications’ senior author, S F Akbar Velthut, Senior Vice President, Investigative Science and Technology, Linus Pauling Institute:

How did you achieve this compound?

This new compound is a first step in clinical development. For tumor progression studies, we realized that the enzyme identified in this novel bioengineered compound would be sensitive enough to block immunosuppressive drug induced cell growth. Thanks to this discovery, we will be able to create the first non-immunosuppressive treatment platform for immunosuppressed patients.”