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 agent resistance in multiple myeloma (MM)^[1].

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

500.52

C₂₅H₂₇F₃N₆O₂

1620820-12-3

Solid

White to off-white

O=C(C1=CC=C(C(OC2=NC=NC(NC)=C2)=C1)C)NC3=CC(C(F)(F)F)=CC(N4CCN(CC4)C)=C3

Room temperature in continental US; may vary elsewhere.

-20°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [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.  [Content Brief]