INY-03-041 trihydrochloride
PRODUCTS SPECIFICATIONS
DESCRIPTION
Overview
| MDL | - |
|---|---|
| Molecular Weight | 907.80 |
| Molecular Formula | C44H59Cl4N7O5 |
| SMILES | O=C(C(N(CC1=C2C=CC=C1CCCCCCCCCCNC[C@H](C3=CC=C(Cl)C=C3)C(N4CCN(C5=C([C@H](C)C[C@H]6O)C6=NC=N5)CC4)=O)C2=O)CC7)NC7=O.Cl.Cl.Cl |
Summary
INY-03-041 trihydrochloride is a potent, highly selective and PROTAC-based pan- AKT degrader consisting of the ATP-competitive AKT inhibitor Ipatasertib (HY-15186) conjugated to Lenalidomide (HY-A0003, Cereblon ligand). INY-03-041 trihydrochloride inhibits AKT1 , AKT2 and AKT3 with IC 50 s of 2.0, 6.8 and 3.5 nM, respectively [1] .
IC50 & Target
|
Akt1 2.0 nM (IC 50 ) |
Akt3 3.5 nM (IC 50 ) |
Akt2 6.8 nM (IC 50 ) |
Cereblon
|
In Vitro
INY-03-041 (10-1000 nM; 0-24 hours) induces potent degradation of all three AKT isoforms in MDA-MB-468 cells
[1]
.
INY-03-041 exhibits potent in vitro inhibition of S6K1 (IC
50
=37.3 nM) and PKG1 (IC
50
= 33.2 nM)
[1]
.
INY-03-041 displays enhanced anti-proliferative effects compared with
Ipatasertib
(HY-15186) in MDA-MB-468 and HCC1937 cells
[1]
.
INY-03-041 (250 nM, 12 h) promotes sustained AKT degradation and inhibition of downstream signaling effects for up to 96 h, even after compound washout
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis [1]
| Cell Line: | MDA-MB-468 cells |
| Concentration: | 0, 10, 50, 100, 250, 500, and 1000 nM |
| Incubation Time: | 0, 2, 4, 6, 8. 10, 12, and 24 h |
| Result: | Induced 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
-20°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
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.
- [2] Maira SM, et al. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol Cancer Ther. 2012 Feb;11(2):317-28.
