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T-3775440 hydrochloride is a potent, selecitve, irreversible LSD1 inhibitor with IC50 value of 2.1 nM. T-3775440 is highly selective for LSD1 relative to other monoamine oxidases (e.g., MAO-A and MAO-B), with IC50 value of 2.1 nM. In CMK11-5 cells, CD86 mRNA expression is also clearly upregulated by T-3775440 in a concentration-dependent manner, although only a modest increase in cell surface CD86 expression is observed. T-3775440 treatment disrupts the LSD1-GFI1B association in a concentration-dependent manner. T-3775440 decreases LSD1 binding but not GFI1B binding and increases the level of dimethylated H3K4 at the PI16 locus.
In a TF-1a (AEL) tumor xenograft model, T-3775440 exhibits significant antitumor effects, with 15-day T/C values of 15.6% and <0% at doses of 20 and 40 mg/kg, respectively. T-3775440 also exhibits potent antitumor effects in an additional AEL model of HEL 92.1.7 and an AMKL model of CMK11-5, leading to nearly complete tumor growth suppression during the dosing period.
| Molecular Weight | 346.85 |
| Formula | C18H23ClN4O |
| CAS Number | 1422535-52-1 |
| Solubility (25°C) | DMSO ≥ 25 mg/mL Water ≥ 10 mg/mL |
| Storage | -20°C, dry, protect from light, sealed |
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