1164471-33-3

TT-012 specifically binds to dynamic MITF and destroys the latter's dimer formation and DNA-binding ability. TT-012 inhibits the transcriptional activity of MITF in B16F10 melanoma cells. TT-012 inhibits the growth of high-MITF melanoma cells, and inhibits the tumor growth and metastasis with tolerable toxicity to liver and immune cells in animal models[1].

Potent and selective MITF dimerization disruptor with significant efficacy against melanoma both in vitro and in vivo.
TT-012 is a highly effective microphthalmia-associated transcription factor (MITF) dimerization inhibitor (Kd = 15.5 nM for the bHLH-LZ domain) th at specifically targets melanoma by disrupting MITFμs DNA-binding activity. TT012 exhibits notable potency in inhibiting MITF dimer formation (IC50 = 13.1 nM) and reducing the growth of B16F10 melanoma cells (IC50 = 499 nM)while also lowering mRNA levels of MITF target genes in these cells (IC50 < 3.12 μM). TT 012 is particularly effective against melanoma cells with elevated MITF expression and markedly diminishes tumor growth and pulmonary metastasis in miceachieving reductions of 79.7% and 93.9% at dosages of 2 mg/kg and 5 mg/kg respectivelycompared to controls.

[1] Liu Z, et al. A unique hyperdynamic dimer interface permits small molecule perturbation of the melanoma oncoprotein MITF for melanoma therapy. Cell Res. 2023 Jan;33(1):55-70. DOI:10.1038/s41422-022-00744-5