| Identification | Back Directory | [Name]
INDEX NAME NOT YET ASSIGNED | [CAS]
2503017-97-6 | [Synonyms]
| [Molecular Formula]
C44H56ClN7O5 | [Molecular Weight]
798.41 |
| Chemical Properties | Back Directory | [Boiling point ]
997.6±65.0 °C(Predicted) | [density ]
1.273±0.06 g/cm3(Predicted) | [storage temp. ]
-20°C, away from moisture | [solubility ]
DMSO : 115 mg/mL (144.04 mM; ultrasonic and warming and heat to 80°C) | [form ]
Solid | [pka]
10.74±0.40(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Biological Activity]
INY-03-041 is a potent, highly selective and PROTAC-based pan-AKT degrader consisting of the ATP-competitive AKT inhibitor GDC-0068 conjugated to Lenalidomide (Cereblon ligand). INY-03-041 inhibits AKT1, AKT2 and AKT3 with IC50s of 2.0 nM, 6.8 nM and 3.5 nM, respectively[1].
INY-03-041 (10-1000 nM; 2-24 hours; MDA-MB-468 cells) treatment induces potent degradation of all three AKT isoforms in a dose-dependent manner after a 12-h treatment, with maximal degradation observed between 100 and 250 nM. At concentrations of 500 nM and greater, AKT degradation is diminished. Treatment with 250 nM of INY-03-041 over time reveals partial degradation of all AKT isoforms within 4 h and progressive loss of AKT abundance out to 24 h[1].INY-03-041 exhibits potent in vitro inhibition of S6K1 (IC50 =37.3 nM) and PKG1 (IC50 = 33.2 nM)[1].INY-03-041 displays enhanced anti-proliferative effects compared with GDC-0068 in MDA-MB-468 and HCC1937 cells[1]. | [References]
[1]. You I, et al. Discovery of an AKT Degrader with Prolonged Inhibition of Downstream Signaling. Cell Chem Biol. 2020 Jan 16;27(1):66-73.e7. |
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