Enzyme Modulators

A specific inhibitor of Bone Morphogenetic Protein (BMP) type 1 receptors ALK2 and ALK3 (IC50  < 0.5 µM). Dorsomorphin analog that exclusively targets the BMP but not VEGF signaling. It is able to inhibit the BMP-induced Smad1/5/8 activation but not the p38/MAP kinase signaling or Activin A-induced Smad2 activation.

Carmofur is an antineoplastic agent that is used to treat various cancers such as breast and colorectal cancer. This drug is a derivative of fluorouracil. Carmofur is an inhibitor of the human acid ceramidase, a lysosomal amidase involved in the development of cancer cells.

Sorafenib is a drug that belongs to the class of multikinase inhibitors. It inhibits a number of kinases, including the Mcl-1 protein, which is involved in apoptosis along with blocking picolinic acid (PA), an endogenous metabolite involved in apoptosis signal transduction. Sorafenib also binds to epidermal growth factor receptor (EGFR) on the surface of cancer cells, inhibiting the production of proteins that are required for angiogenesis, thus blocking the formation of new blood vessels. Sorafenib may also inhibit P-glycoprotein (Pgp) activity. Overall, these cytotoxic effects give Sorafenib anti-tumor properties, inhibiting angiogenesis and cellular transformation, which are the two main processes of tumor growth and metastasis. Sorafenib tosylate has been shown to be effective against a range of solid tumors such as breast, prostate and lung cancers and is also used for the treatment of metastatic colorectal cancer and renal cell carcinoma. A combination therapy group found that sorafenib was more effective when used with interferon alfa-2b for the treatment of advanced renal cell carcinoma. Sorafenib also has the potential for drug interactions with other drugs that are metabolized by cytochrome P450 enzymes.

Inhibitor of pan-class I PI3K family of lipid kinases; antineoplastic

Inhibits interaction between small GTPase Rab27a and its effector JFC1 (synaptotagmin-like protein1, Slp1). These proteins regulate neutrophil exocytosis, decrease neutrophil infiltration in liver and kidneys and reduce extracellular ROS production by NAPDH oxidase. Thus, nexinhibib20 suppresses systemic inflammation.

Inhibits non-receptor tyrosine kinase BTK; antineoplastic

Potent and selective inhibitor of histone deacetylase 6 (HDAC6) with IC50 of 2.4 nM. Its anti-inflammatory activity was examined in a mouse model for acute colitis. The compound protected from intestinal inflammation by prevention of infiltration of CD19+ B-cells into the lamina propria of colonic epithelium and attenuated neutrophil activation. Its broad anti-inflammatory response involved decrease in 24 inflammatory chemokines and cytokines. Also, it is a potent inhibitor of cell proliferation in pancreatic cancer cell lines.

Short acting monoamine oxidase inhibitor