Enzyme Modulators

<p>Proteosome inhibitor; pro-apoptotic; has anti-myeloma activity</p>

<p>Phosphodiesterase 5 inhibitor; anti-impotence drug</p>

<p>Gefitinib is an inhibitor of the epidermal growth factor receptor (EGFR) protein. This inhibition is on the EGFR tyrosine kinase domain, where Gefitinib bindings to the ATP-binding site. As a a tyrosine kinase inhibitor, Gefitinib blocks tumor growth and has led to its use in slowing the progression of non-small cell lung cancer. Gefitinib also inhibits invasion and metastasis through inhibition of macrophage receptor interacting protein kinase 2 (RIPK2), rather than EGFR.</p>

<p>Phosphodiesterase inhibitor</p>

<p>O6-Benzylguanine is a guanine analog that is an antineoplastic agent. It works by acting as a suicide inhibitor of the enzyme O6-alkylguanine-DNA alkyltransferase. This results to an interruption of DNA repair so that damage can occur to local tumor targets.</p>

<p>Inhibits multiple receptor tyrosine kinases (RTKs), including c-Kit, PDGFRβ, PDGFRα, c-Met, and Axl. Sitravatinib inhibits proliferation of sarcoma cells and reduced tumor growth in vivo. Promotes immune response in tumor microenvironment and enhances sensitivity to immune checkpoint inhibitors. This compound is undergoing several clinical trials as a potential anti-cancer therapeutic agent.</p>

<p>Inhibitor of 3β-hydroxysteroid dehydrogenase in steroid biosynthesis</p>

<p>Potent and selective MAP/ERK kinase 1/2 inhibitor. Reduces growth of tumor cells with B-Raf and Ras mutations. Tumor regression observed after chronic treatment in in vivo xenograft models. Enhances anti-tumor effect in combination with irinotecan or docetaxel.</p>

<p>Inhibitor of CDK4/6 serine/threonine kinases; antineoplastic</p>

<p>Abiraterone is an antiandrogen drug used in the treatment of metastatic prostate cancer. It is a derivative of steroidal progesterone. This drug inhibits the enzyme CYP17 irreversibly, thus inhibiting the synthesis of androgen. It specifically inhibits the conversion of 17-hydroxyprognenolone to dehydroepiandrosterone to decrease serum levels of testosterone and other androgens.</p>

<p>Topoisomerase II inhibitor; chemotherapeutic drug</p>

<p>Diacerein is a slow-onset anthraquinone IL-1 inhibitor that is used in the treatment of joint diseases such as osteoarthritis. This drug is also being studied for the treatment of insulin resistance and diabetes mellitus. Diacerein works to decrease inflammation and cartilage destruction by reducing the level of interleukin-1.</p>

<p>Inhibitor of cytochrome P450; inhibitor of prostaglandin synthesis</p>

<p>Imiquimod is a toll-like receptor 7 agonist drug that is used for the treatment of genital warts, basal cell carcinoma and condyloma acuminata. This drug works by relieving and controlling wart production. Studies in mice have shown that this drug may induce cytokines such as interleukins. Imiquimod helps to increase apoptosis of diseased tissues and an infiltration of lymphocytes into tumor lesions.</p>

<p>Inhibits phorbol ester TPA/PMA; immunosuppressant</p>

<p>Lenalidomide is a thalidomide derivative that is used to treat multiple myeloma and anemia. This drug exerts immunomodulatory effects by altering cytokine production. Lenalidomide also directly inhibits the cullin ring E3 ubiquitin ligase complex.</p>

<p>Leflunomide is a pyrimidine synthesis inhibitor drug that is used to treat rheumatoid arthritis. Although its mechanism of action is not fully determined, this drug has shown to interfere with cell cycle progression by inhibiting dihydroorotate dehydrogenase and has shown antiproliferative activity. As a result of this, it interferes with the expansion of activated autoimmune lymphocytes. Additionally, Leflunomide is a tyrosine kinase inhibitor.</p>

<p>NButGT (N-butyryl-glucosamine-1,5-lactone O-(phenylcarbamoyl)oxime) is a selective inhibitor of O-GlcNAcase (OGA), the enzyme responsible for removing O-linked N-acetylglucosamine (O-GlcNAc) modifications from proteins. It effectively increases O-GlcNAc levels in cells and tissues without altering hexosamine biosynthetic pathway enzyme expression. It has also been shown that NButGT rapidly increases O-GlcNAcylation of mitochondrial proteins involved in oxidative phosphorylation and metabolism. While effective, NButGT served as a precursor to more potent OGA inhibitors like Thiamet-G. These findings highlight NButGT's importance as a tool for studying O-GlcNAcylation in various biological contexts, particularly in cardiac and neurological research. For example, in recent cardiac studies, NButGT pretreatment has demonstrated an improvement in cardiac output and mitochondrial respiration when combined with epinephrine.</p>

<p>Inhibitor of oxidative phosphorylation which acts on the F0F1 ATP synthase in the inner mitochondrial membrane and causes acute increase in mitochondrial membrane potential. Gboxin was shown to accumulate in mitochondria of cancer cells, to cause cellular toxicity and cell growth inhibition in mouse glioblastoma. However, Gboxin did not inhibit growth of mouse embryonic fibroblasts or neonatal astrocytes.</p>

<p>Inhibitor of factor Xa</p>