| Identification | Back Directory | [Name]
(S)-2-Amino-4-(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)-1-(isoindolin-2-yl)butane-1,4-dione | [CAS]
847928-32-9 | [Synonyms]
1G244
(S)-2-Amino-4-(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)-1-(isoindolin-2-yl)butane-1,4-dione
2-Amino-4-[4-[bis(4-fluorophenyl)methyl]-1-piperazinyl]-1-(1,3-dihydro-2H-isoindol-2-yl)-1,4-butaned
(2S)-2-amino-4-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-1-(1,3-dihydroisoindol-2-yl)butane-1,4-dione
1,4-Butanedione, 2-amino-4-[4-[bis(4-fluorophenyl)methyl]-1-piperazinyl]-1-(1,3-dihydro-2H-isoindol-2-yl)-, (2S)- | [Molecular Formula]
C29H30F2N4O2 | [MOL File]
847928-32-9.mol | [Molecular Weight]
504.57 |
| Chemical Properties | Back Directory | [Boiling point ]
674.3±55.0 °C(Predicted) | [density ]
1.304±0.06 g/cm3(Predicted) | [storage temp. ]
Keep in dark place,Sealed in dry,2-8°C | [solubility ]
Soluble in DMSO (>20 mg/ml) | [form ]
solid | [pka]
7.25±0.33(Predicted) | [color ]
Off-white | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months. |
| Hazard Information | Back Directory | [Description]
1G244 (847928-32-9) is a potent and selective inhibitor of the prolyl dipeptidases DPP8 (IC50 = 14 nM) and DPP9 (IC50 = 53 nM).1,2? It does not inhibit DPP2, DPP4 or fibroblast activation protein (FAP) at 100 μM.1,2 1G244 is a slow binding competitive inhibitor of DPP8 but a competitive and reversible inhibitor of DPP9.2? Inhibition of DPP8/9 by 1G244 has been shown to cause pro-caspase-1-dependent pyroptosis in macrophages and monocytes.3 1G244 also induced cell death in DPP8/9 knockout cells at higher concentration indicating there may be some off-target effects.3 1G244 blocks adipogenesis in preadipocyte 3T3-L1 and 3T3-F422A cells.4? DPP8/9 inhibition attenuates PPARg2 induction during preadipocyte differentiation.4 Because of its inhibitory effects on pro-inflammatory macrophages, 1G244 inhibition of DPP8/9 has been examined as a potential therapy for reducing atherosclerosis and/or in the prevention of plaque rupture.5,6 Cell permeable. | [Uses]
1G244 is a potent DPP8/9 inhibitor with IC50s of 12 nM and 84 nM, respectively. 1G244 does not inhibit DPPIV and DPPII. 1G244 induces apoptosis in multiple myeloma cells and has anti-myeloma effects[1][2]. | [in vivo]
1G244 (30 mg/kg; subcutaneous injection; once-a-week; for 3 weeks; NOG female mice) treatment apparently suppresses the subcutaneous growth of MM.1 S cells in murine xenograft model[1]. | Animal Model: | NOD/Shi-scid IL-2Rγnull (NOG) female mice (6-7 weeks; 19-21?g) injected with MM.1?S cells[1] | | Dosage: | 30 mg/kg | | Administration: | Subcutaneous injection; once-a-week; for 3 weeks | | Result: | Apparently suppressed the subcutaneous growth of MM.1?S cells in murine xenograft model.
|
| [IC 50]
DPP-4 | [storage]
4°C, away from moisture and light | [References]
Jiaang et al. (2005), Novel isoindoline compounds for potent and selective inhibition of prolyl dipeptidase DPP8; Bioorg.Med.Chem.Lett.15 687
Wu et al. (2009), Biochemistry, pharmacokinetics, and toxicology of a potent and selective DPP8/9 inhibitor; Biochem.Pharmacol. 78 203
Okondo et al. (2017), DPP8/9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis; Nat.Chem.Biol. 13 46
Han et al. (2015), Inhibition of dipeptidyl peptidase 8/9 impairs preadipocyte differentiation; Sci.Rep. 5 12348
Matheeussen et al. (2013), Dipeptidyl peptidases in atherosclerosis: expression and role in macrophage differentiation, activation and apoptosis; Basic Res.Cardiol. 108 350
Waumans et al. (2016), The Dipeptidyl Peptidases 4,8, and 9 in Mouse Monocytes and Macrophages: DPP8/9 Inhibition Attenuates M1 Macrophage Activation in Mice; Inflammation 39 413 |
|
|