1,4-DPCA

1,4-DPCA potently inhibits collagen prolyl-4-hydroxylase (P4H; IC50 ~ 2 µM), HIF-prolyl hydroxylase, and TET1/TET2 enzymes (pIC50 5.42/5.26), impacting collagen biosynthesis, hypoxia signaling, and DNA demethylation. Through 2-oxoglutarate competition, it reduces proline hydroxylation, stabilizes HIF-1α protein levels, affecting collagen maturation, decreasing CD44+/CD24-/low cancer stem cells, and modulating α-KG/succinate levels. Consequently, 1,4-DPCA demonstrates significant anti-cancer effects in breast cancer models, inhibiting tumor growth, metastasis, and altering cellular metabolism via downregulation of HIF-1 targets LDHA/PDK1. FG-0041 in combination with Y-27632 initiates differentiation of mesenchymal stem cells into neuron-like cells. Notably, DPCA enhances CAR-T cell expansion and function, improving chemotherapeutic efficacy, potentially by affecting oxygen consumption, extracellular acidification, and reactive oxygen species levels.