Arginase 1 and Tubulin beta chain (ARG1; TUBB)

This entry describes two distinct therapeutic targets: Arginase 1 (ARG1) and Tubulin beta chain (TUBB). Arginase 1 is a manganese-containing enzyme that catalyzes the hydrolysis of L-arginine to urea and L-ornithine, playing a critical role in the urea cycle and immune regulation [1]. In the context of oncology, Arginase 1 is often overexpressed by myeloid-derived suppressor cells in the tumor microenvironment, leading to arginine depletion which suppresses T-cell and natural killer cell activity [2]. INCB001158 (numidargistat) is a small-molecule inhibitor of Arginase 1 designed to restore arginine levels and promote an anti-tumor immune response [2]. Tubulin beta chain is a major structural component of microtubules, which are dynamic polymers essential for maintaining cell shape, facilitating intracellular transport, and forming the mitotic spindle during cell division [3]. Paclitaxel is a microtubule-stabilizing agent that binds to the beta-tubulin subunit, inhibiting the disassembly of microtubules and causing cell cycle arrest at the G2/M phase, which ultimately triggers apoptosis in rapidly dividing cancer cells [4]. These two targets are frequently investigated together in clinical trials to evaluate the efficacy of combining immune-checkpoint modulation with direct cytotoxic chemotherapy [5].

Other names

Arginase ILiver-type arginaseBeta-tubulinTubulin beta-5 chainMicrotubule-associated tubulin

INCB001158 is a small-molecule inhibitor of Arginase 1 that prevents the degradation of L-arginine in the tumor microenvironment, thereby reversing myeloid-mediated immune suppression; Paclitaxel is a taxane that binds to the beta-subunit of tubulin to stabilize microtubules and induce mitotic arrest.