1620820-12-3

1620820-12-3 structure

Name: TL4-12
Chemical Name: 4-Methyl-3-{[6-(methylamino)-4-pyrimidinyl]oxy}-N-[3-(4-methyl-1-piperazinyl)-5-(trifluoromethyl)phenyl]benzamide
CAS Number: 1620820-12-3
Molecular Formula: C₂₅H₂₇F₃N₆O₂
Molecular Weight: 500.516
Catalog: Signaling Pathways Apoptosis Apoptosis
Create Date: 2021-01-09 11:25:20
Modify Date: 2024-01-16 20:43:20
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].

Name	4-Methyl-3-{[6-(methylamino)-4-pyrimidinyl]oxy}-N-[3-(4-methyl-1-piperazinyl)-5-(trifluoromethyl)phenyl]benzamide
Synonyms	4-Methyl-3-{[6-(methylamino)-4-pyrimidinyl]oxy}-N-[3-(4-methyl-1-piperazinyl)-5-(trifluoromethyl)phenyl]benzamide Benzamide, 4-methyl-3-[[6-(methylamino)-4-pyrimidinyl]oxy]-N-[3-(4-methyl-1-piperazinyl)-5-(trifluoromethyl)phenyl]-

Description	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].
Related Catalog	Signaling Pathways >> MAPK/ERK Pathway >> MAP4K Signaling Pathways >> Apoptosis >> Apoptosis Research Areas >> Cancer Research Areas >> Inflammation/Immunology
In Vitro	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].
References	[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.