HA-15

GRP78抑制剂；在无细胞测定中与GRP79结合，并增加编码UPR蛋白EIF2AK3、IRE1α、ATF6、DDIT3和XBP1的基因以及凋亡相关基因JUN和BCL2和自噬标记基因LC3的表达；降低A375黑色素瘤细胞的活力(IC50=2.5µM)；在A375小鼠异种移植模型中以0.7mg/只/天的剂量减少肿瘤体积并诱导肿瘤内细胞凋亡和自噬；在卵巢切除术引起的骨质疏松症小鼠模型中增加成骨作用并减少骨质流失。An inhibitor of GRP78; binds to GRP79 in a cell-free assay and increases the expression of the genes encoding the UPR proteins EIF2AK3, IRE1α, ATF6, DDIT3, and XBP1, as well as the apoptosis-associated genes JUN and BCL2 and the autophagy marker gene LC3; decreases the viability of A375 melanoma cells (IC50 = 2.5 µM); reduces tumor volume and induces intratumor apoptosis and autophagy in an A375 mouse xenograft model at 0.7 mg/animal per day; increases osteogenesis and reduces bone loss in a mouse model of ovariectomy-induced osteoporosis.分子式C23H22N4O3S2分子量466.6O=C(C)NC1=NC(C2=CC(NS(=O)(C3=CC=CC4=C(N(C)C)C=CC=C43)=O)=CC=C2)=CS1