TL4-12

TL4-12 is a selective MAP4K2/GCK inhibitor, dose-dependently downregulates IKZF1 and BCL-6 and leads to MM cell proliferation inhibition (IC50=37 nM) accompanied by induction of apoptosis. TL4-12 can be used to overcome immunomodulatory drug resistance in multiple myeloma (MM)[1].

Signaling Pathways >> MAPK/ERK Pathway >> MAP4K

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Research Areas >> Inflammation/Immunology

TL4 12 (0-5 µM; 4 days) shows antiproliferation activity with an IC50 value of 37 nM for MM cells, and with IC50s of 1.62, 3.7, 4.4, 5.7, 10, 32, 49, 19 µM for JJN3, MM1.S, H929, RPMI-8226, MOLP-8, SKMM2, LP-1, U266 cells, respectively[1]. .TL4-12 (0, 1, 3 µM; 24 h) dose-dependently decreases IKZF1, c-MYC, and BCL-6 protein expression and increases p53 level in K-RASG12A MM.1S cells[1]. TL4-12 dose-dependently increases Annexin-V positive cell from 6% (dimethyl sulfoxide) to 13% (1 μM) and 22% (3 μM), respectively[1]. TL4-12 induces apoptosis and cell-cycle arrest in the G0/G1 phase in MM.1S, RPMI-8226, RPMI-8226 cells[1].

[1]. Shirong Li, et al. Targeting the GCK pathway: a novel and selective therapeutic strategy against RAS-mutated multiple myeloma. Blood. 2021 Apr 1;137(13):1754-1764.