TBC3486

TBC3486 is a highly selective integrin α4β1 inhibitor. TBC3486 acts as a chemosensitizer to enhance the sensitivity of leukemia cells to chemotherapy. TBC3486 exhibits efficacy in preclinical models of integrin α4-dependent inflammatory and autoimmune diseases, including a mouse model of autoimmune encephalomyelitis. TBC3486 can be used for the research of precursor B-cell acute lymphoblastic leukemia^[1]. In Vitro:TBC3486 (5-25 μM; 4 days) dose-dependently reduces adhesion of pre-B-ALL LAX7R cells to OP9 stromal cells^[1].
TBC3486 (25 μM; 4 days) specifically downregulates integrin α4 expression in pre-B-ALL LAX7R cells without altering integrin α5 or integrin α6 expression^[1].
TBC3486 (25 μM; 2 days) significantly reduces adhesion of pre-B-ALL LAX7R, ICN3, and SFO3 cells to human VCAM-1, with the greatest effect observed in CD49d-high LAX7R cells^[1].
TBC3486 (25 μM; 2 days) does not affect the viability of pre-B-ALL LAX7R, ICN3, or SFO3 cells^[1].
TBC3486 (25 μM; 4 days, in combination with VDL chemotherapy) sensitizes pre-B-ALL LAX7R, ICN3, and SFO3 cells to Vincristine (HY-N0488A), Dexamethasone (HY-14648) and L-asparaginase (HY-P1923) chemotherapy, significantly reducing cell viability compared to chemotherapy alone^[1]. In Vivo:TBC3486 (10 mg/kg/day; i.p.; two injections per day; daily for 2 weeks) prolongs survival of NOD/SCID mice bearing human LAX7R pre-B-ALL xenografts, with a median survival time of 41 days as monotherapy and 82 days when combined with VDL chemotherapy^[1].