NCI Drug Dictionary

The NCI Drug Dictionary contains technical definitions and synonyms for drugs/agents used to treat patients with cancer or conditions related to cancer. Each drug entry includes links to check for clinical trials listed in NCI's List of Cancer Clinical Trials.

racemetyrosine/methoxsalen/phenytoin/sirolimus SM-88
A combination agent containing racemetyrosine, methoxsalen, phenytoin and sirolimus, with potential antineoplastic activity. Upon administration of racemetyrosine/methoxsalen/phenytoin/sirolimus SM-88, racemetyrosine, being a dysfunctional and modified form of the non-essential amino acid tyrosine, is specifically taken up by cancer cells through the transporter L-amino acid transferase-1 (LAT1; CD98). As a tyrosine derivative and faulty amino acid protein building block, racemetyrosine prevents protein synthesis in cancer cells. Specifically, this prevents mucin-1 (MUC1) protein synthesis. MUC1 is highly overexpressed by most cancer cells and regulates the increased reactive oxygen species (ROS) in cancer cells created from the altered metabolism that cancer cells utilize, by upregulating key antioxidant defenses and preventing ROS-mediated apoptosis. In the absence of MUC1, ROS levels are increased, leading to an increase in oxidative stress, and induction of apoptosis. Also, being a protective transmembrane protein, MUC1 is part of the protective layer on the outside of cancer cells and plays a key role in shielding the cancer cell from the immune system. The loss of MUC1 compromises the cell membrane, thereby making the cancer cell more vulnerable to be recognized and attacked by the immune system. Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, increases the cancer cells' need for tyrosine uptake and increases the uptake of racemetyrosine by LAT1. Phenytoin stimulates the release of reactive lipid species by the liver which accumulate in the tumor microenvironment (TME) and are taken up by cancer cells, thereby further increasing ROS within the cancer cell and increasing oxidative-related apoptosis. Mehoxsalen promotes toxic electron transfer and increases melanin, increases oxidative reactions and production of ROS. This further stimulates oxidative stress-mediated apoptosis. Normal cells do not regularly take up certain non-essential amino acids, such as tyrosine, but readily convert phenylalanine to tyrosine, so normal healthy cells are not expected to consume racemetyrosine. Check for active clinical trials using this agent. (NCI Thesaurus)

Synonym:racemetyrosine/methoxsalen/phenytoin/sirolimus combination SM88
SM-88 used with methoxsalen/phenytoin/sirolimus
SM-88 used with MPS
tyrosine isomers/phenytoin/methoxsalen/sirolimus
Code name:SM-88