Olitigaltin

Olitigaltin (TD139) is a high-affinity Galectin-3 inhibitor with a K_d value of 14 nM. Olitigaltin inhibits the activity of the AKT/β-catenin pathway, induces Apoptosis, and downregulates SREBP1 expression. Olitigaltin enhances the phosphorylation level of ERK. Olitigaltin alleviates bleomycin (HY-17565A)-induced advanced pulmonary fibrosis in mice. Olitigaltin delays the onset of diabetes, and improves glucose tolerance and serum insulin levels. Olitigaltin alleviates liver injury. Olitigaltin maintains the structure of hippocampal excitatory synapses, restores γ-wave power in the hippocampal CA1 region, inhibits hippocampal neuroinflammation, and improves cognitive function in neuroinflammation models. Olitigaltin can be used in research related to thyroid cancer, idiopathic pulmonary fibrosis, type 1 diabetes, hepatitis, and cognitive dysfunction induced by neuroinflammation^{[1][2][3][4][5][6]}. IC50 & Target:Kd: 14 nM (galectin-3)^[1] In Vitro:Olitigaltin (10-100 μM; 24-72 h) reduces cell viability in a dose-dependent manner in FTC-133 and 8505C thyroid cancer cells (inducing 41.1-49.7% viability reduction at 100 μM for 72 h) but does not affect viability in Nthy-ori 3-1 thyroid follicular epithelial cells^[1].
Olitigaltin (10-100 μM; 10 days) abrogates the colony-forming ability of FTC-133 and 8505C thyroid cancer cells at 100 μM over 10 days^[1].
Olitigaltin (10-100 μM; 24 h) inhibits migration and invasion in a dose-dependent manner in FTC-133 and 8505C thyroid cancer cells at 10 and 100 μM for 24 h, but stimulates invasion in Nthy-ori 3-1 thyroid follicular epithelial cells at 100 μM for 24 h^[1].
Olitigaltin (10-100 μM; 24 h) induces apoptosis in FTC-133 and 8505C thyroid cancer cells, increasing sub-G1 cell populations to 31.3% and 35.0% respectively at 100 μM for 24 h^[1].
Olitigaltin (10-100 μM; 24 h) modulates key signaling and apoptotic proteins in FTC-133 and 8505C thyroid cancer cells at 10 and 100 μM for 24 h, inducing apoptosis, attenuating AKT phosphorylation, reducing β-catenin and MMP2 expression, and increasing ERK phosphorylation^[1].
Olitigaltin (10 μM; 24-48 h) attenuates SREBP1 mRNA expression in a time-dependent manner in both BHT-101 and FTC-133 thyroid cancer cells, likely independent of AKT phosphorylation^[3]. In Vivo:Olitigaltin (10 mg; i.t.; 4 doses (Days 18, 20, 22, 24 post-bleomycin instillation)) attenuates late-stage Bleomycin (HY-17565A)-induced lung fibrosis in female C57/Bl6 mice, reducing total lung collagen content and histologic fibrosis score while inhibiting β-catenin activation^[2].
Olitigaltin (15 mg/kg; i.p.; daily; 8 weeks) delays diabetes onset, reduces diabetes incidence to 20.0% by 30 weeks of age, improves glucose tolerance and pancreatic β cell function, and modulates islet immune cell populations in female NOD mice with spontaneous type 1 diabetes^[4].
Olitigaltin (15 mg/kg; i.p.; once daily; 7 days) mitigates LPS-induced neuroinflammation, preserves excitatory synapses, restores hippocampal gamma oscillations, and improves cognitive function in male C57BL/6J mice^[6].