Proline Isomerization: From the Chemistry and Biology to Therapeutic Opportunities.

Proline isomerization, the process of interconversion between the - and -forms of proline, is an important and unique post-translational modification that can affect protein folding and conformations, and ultimately regulate protein functions and biological pathways. Although impactful, the importance and prevalence of proline isomerization as a regulation mechanism in biological systems have not been fully understood or recognized. Aiming to fill gaps and bring new awareness, we attempt to provide a wholistic review on proline isomerization that firstly covers what proline isomerization is and the basic chemistry behind it.

Therapeutic Activity of the Lansoprazole Metabolite 5-Hydroxy Lansoprazole Sulfide in Triple-Negative Breast Cancer by Inhibiting the Enoyl Reductase of Fatty Acid Synthase.

Fatty acid synthase (FASN), a sole cytosolic enzyme responsible for de-novo lipid synthesis, is overexpressed in cancer but not in normal non-lipogenic tissues. FASN has been targeted, albeit no such inhibitor has been approved. Proton pump inhibitors (PPIs), approved for digestive disorders, were found to inhibit FASN with anticancer activities in attempting to repurpose Food and Drug Administration-approved drugs.

Proton pump inhibitors suppress DNA damage repair and sensitize treatment resistance in breast cancer by targeting fatty acid synthase.

Human fatty acid synthase (FASN) is the sole cytosolic enzyme responsible for de novo lipid synthesis. FASN is essential for cancer cell survival and contributes to drug and radiation resistance by up-regulating DNA damage repair but not required for most non-lipogenic tissues. Thus, FASN is an attractive target for drug discovery.