| Chemical Properties | Back Directory | [Boiling point ]
762.074±60.00 °C(Press: 760.00 Torr)(predicted) | [density ]
1.322±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted) | [form ]
Solid | [pka]
8.444±0.10(predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
Menin-MLL inhibitor-22 (compound C20) is an orally active inhibitor of the interaction between menin and mixed lineage leukemia (MLL) (IC50=7 nM). Menin-MLL inhibitor-22 binds menin protein and inhibits cancer cell growth (MV4 cells, IC50=0.3 μM). Menin is a putative tumor suppressor associated with multiple endocrine neoplasia type 1 (MEN-1 syndrome)[1]. | [in vivo]
Menin-MLL inhibitor-22 (6 mg/kg and 30 mg/kg; p.o.; every second day for 16 days) shows potent antitumor activity in the MV4;11 subcutaneous xenograft models of MLL-rearranged leukemia[1].
Pharmacokinetic Properties in SD Rats[1]
| Route | Dose (mg/kg) | Tmax (h) | T1/2 (h) | MRT (h) | Cmax (ng/mL) | AUC0-t (ng·h/mL) | AUC0-∞ (ng·h/mL) | Cltotal (mL/h/kg) | Vss (L/kg) | F (%) | | i.v. | 5 | N/A | 17.5 | 7.1 | 1187 | 1700 | 2495 | 2056 | 49.3 | | | p.o. | 15 | 7.3 | 15.5 | 12.0 | 56.7 | 863.7 | 1476 | 10730 | 23 | 16.9 |
| Animal Model: | Balb/C nude mice bearing MV4;11 cell xenografts[1] | | Dosage: | 6 mg/kg, 30 mg/kg | | Administration: | Oral gavage; every second day for 16 days | | Result: | Reduced the volume of tumor in mice. |
| [References]
[1] Lei H, et al. Discovery of Novel, Potent, and Selective Small-Molecule Menin-Mixed Lineage Leukemia Interaction Inhibitors through Attempting Introduction of Hydrophilic Groups. J Med Chem. 2022 Oct 13;65(19):13413-13435. DOI:10.1021/acs.jmedchem.2c01313 |
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