Indoleamine 2,3-dioxygenase 1 (IDO1), Small ubiquitin-like modifier 2 (SUMO2), and Profilin-1 (PFN1) (IDO1, SUMO2, PFN1)

This target entry refers to a triad of proteins—Indoleamine 2,3-dioxygenase 1 (IDO1), Small Ubiquitin-like Modifier 2 (SUMO2), and Profilin-1 (PFN1)—that are collectively modulated by the investigational drug OKN-007 in the treatment of glioblastoma [1, 4]. IDO1 is an enzyme that catalyzes the rate-limiting step of tryptophan degradation, creating an immunosuppressive environment that allows tumors to evade the immune system [12, 13]. SUMO2 is a member of the small ubiquitin-like modifier family involved in post-translational modifications that regulate protein stability and stress responses, while PFN1 is an actin-binding protein essential for cytoskeletal remodeling and cell migration [2, 8]. In glioblastoma, these proteins are often dysregulated and contribute to tumor aggressiveness and resistance to standard therapies like temozolomide [1, 16]. OKN-007, a nitrone-based agent, has been shown to downregulate SUMO2 and PFN1 and modulate IDO1 expression, thereby inhibiting tumor growth and reducing angiogenesis [20, 21]. This multi-target modulation is particularly relevant for addressing drug resistance in high-grade gliomas [1, 19]. Clinical studies have explored OKN-007 as a combination therapy to enhance the efficacy of alkylating agents [15, 18]. The interaction with these targets highlights the drug's potential to alter the tumor microenvironment and metabolic landscape [20, 22]. Overall, IDO1, SUMO2, and PFN1 represent a functional cluster of markers for monitoring the therapeutic response to nitrone-based treatments in brain cancer [1, 23].

Other names

IDOINDOIndoleamine-pyrrole 2,3-dioxygenaseSMT3H2SMT3BSentrin-2Profilin I

OKN-007 modulates the expression of IDO1, SUMO2, and PFN1 to inhibit tumor growth, reduce angiogenesis, and overcome temozolomide resistance in glioblastoma [1, 2, 20].