TCRS-417

TCRS-417 (T417) is a small-molecular inhibitor for PBX1. TCRS-417 can directly block PBX1-binding to DNA (IC₅₀ = 6.58 μM), and affects PBX1 transcription. TCRS-417 is able to hammer out the stemness traits of Carboplatin (HY-17393)-resistant (CR) cells to revert to a differentiated status through tacking PBX1 signaling cascade. TCRS-417 significantly suppresses self-renewal and proliferation of cancer cells expressing high levels of PBX1. TCRS-417 can decrease the mRNA levels of FOXM1, NEK2, and E2F2 in cancer cell lines. TCRS-417 is selectively toxic against chr1q-amp myeloma and solid tumor cells^[1][2][3][4]. In Vitro:TCRS-417 (Compound T417) (20 μM, 48 h) results in significant depletion of the G2/M phase, together with G0/1 phase arrest, upon T417 treatment in 4 myeloma (MM.1S, U266, NCU.MM1, OPM2), 2 breast cancer (MCF-7, LTED), 2 ovarian cancer (OVCAR3, A2780), 2 lung cancer (A549, H69AR), and 1 brain cancer (SNB-75) cell lines^[3].
TCRS-417 (20 μM, 16-20 h) significantly decreases the mRNA levels of FOXM1, NEK2, and E2F2 in almost all 11 cell lines^[3].
TCRS-417 (0.625-80 μM) decreases the PBX1 binding to the DNA in a dose-dependent manner^[4].
TCRS-417 (0-10 μM) attenuates the spherogenic capacity and re-directs stem cell-like cells back to a more differentiated state in OVCAR3-CR and SKOV3-CR cell lines^[4]. In Vivo:TCRS-417 (Compound T417) (10 mg/kg, s.c., 23 d) significantly reduces tumor size and weight in xenograft myeloma mice model^[3].
TCRS-417 (5 mg/kg/injection, intratumoral, 3 doses per week over a course of 3 weeks) reduces MEOX1 and BCL6 gene expression in a dose-dependent manner^[4].
TCRS-417 (5 mg/kg/injection, s.c., 3 doses per week over a course of 3 weeks) significantly delays tumor growth and reduced the end point tumor weight of A2780 xenografts when combined with Carboplatin (HY-17393) in immunocompromised nu/nu mice^[4].