RAGE is a cell receptor that is normally activated by several kinds of molecules, including S100 and HMGB1 proteins.
When RAGE is overactivated by these proteins, it is believed to promote and worsen multiple types of cancers and their complications.
Overactivation of the RAGE receptor helps tumors grow and spread (metastasize)
RAGE ligands include the HMGB1 and S100 proteins
Expressed and secreted by cancer cells
Associated with increased metastasis and poorer outcomes in a wide variety of tumors
Ligand binding and activation of RAGE activates intracellular signaling pathways that stimulate cancer growth, invasion, resistance to chemotherapy and radiation, and metastasis
Azeliragon is an investigational oral drug that works by inhibiting RAGE by blocking the attachment of the full spectrum of RAGE ligands
Blocking RAGE inhibits
tumor growth and metastasis
High level of safety and tolerability similar to placebo in 2,237 patients in clinical trials, including patients dosed up to 18 months*
* Primarily in Alzheimer’s disease
Magna M, Hwang GH,McIntosh A, et al. Azeliragon (TTP488), an orally-available small molecule RAGE inhibitor, reduces metastasis in preclinical mouse models of breast cancer. ABSTRACTP4-08-10
- Azeliragon (TTP488) was tested invitro on cancer cell migration and invasion with triple negative breast breast cancer (TNBC) cell lines using 2 types of cells: 1) 4,175 highly metastatic MDA-MB-231 variants, and, 2) 4T-1 cells
- Azeliragon impaired mechanisms of metastasis in both types of cells, affecting multiple metastatic pathways, including focal adhesion, ECM-receptor interaction, cell cycle, and DNA replication
- No deleterious effects on mouse health were observed
Hwang GH. The Role of RAGE Inhibition in Breast Cancer Metastasis. 2022. Dissertation Abstract.
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Azeliragon (TTP488) decreased tumor growth and lung metastasis in preclinical models of metastatic breast cancer
Monteiro C, Miarka L, Perea-Garcia M, et al. Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism. NatMed. 2022;28:752-765.
- Mice were implanted with cancer cells from a woman withTNBC and treated with whole brain radiation with or without RAGE inhibition
- Without RAGE inhibition, TNBC brain metastases were resistant to radiation
- With RAGE inhibition, TNBC brain metastases were almost completely obliterated