(S)-2-Amino-4-(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)-1-(isoindolin-2-yl)butane-1,4-dione

Product Name(S)-2-Amino-4-(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)-1-(isoindolin-2-yl)butane-1,4-dione
CAS847928-32-9
MFC29H30F2N4O2
MW504.57
EINECS
MOL File847928-32-9.mol

Chemical Properties

Boiling point	674.3±55.0 °C(Predicted)
Density	1.304±0.06 g/cm3(Predicted)
storage temp.	2-8°C(protect from light)
solubility	Soluble in DMSO (>20 mg/ml)
pka	7.25±0.33(Predicted)
form	solid
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.
InChIKey	ZKIQFLSGMMYCGS-SANMLTNESA-N
SMILES	O=C(C[C@@H](C(N1CC(C=CC=C2)=C2C1)=O)N)N3CCN(C(C4=CC=C(F)C=C4)C5=CC=C(F)C=C5)CC3

Safety Information

WGK Germany	WGK 3
Storage Class	11 - Combustible Solids

Usage And Synthesis

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; 19-21g) injected with MM.1S cells^[1]
Dosage:	30 mg/kg
Administration:	Subcutaneous injection; once-a-week; for 3 weeks
Result:	Apparently suppressed the subcutaneous growth of MM.1S cells in murine xenograft model.

IC 50

DPP-4

References

[1] WEIR-TORN JIAANG. Novel Isoindoline Compounds for Potent and Selective Inhibition of Prolyl Dipeptidase DPP8.[J]. ChemInform, 2005, 36 25. DOI:10.1002/chin.200525117
[2] JIA-JING WU . Biochemistry, pharmacokinetics, and toxicology of a potent and selective DPP8/9 inhibitor[J]. Biochemical pharmacology, 2009, 78 2: Pages 203-210. DOI:10.1016/j.bcp.2009.03.032
[3] MARIAN C OKONDO. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis[J]. Nature chemical biology, 2016, 13 1: 46-53. DOI:10.1038/nchembio.2229
[4] RUIJUN HAN. Inhibition of dipeptidyl peptidase 8/9 impairs preadipocyte differentiation.[J]. Scientific Reports, 2015: 12348. DOI:10.1038/srep12348
[5] VEERLE MATHEEUSSEN. Dipeptidyl peptidases in atherosclerosis: expression and role in macrophage differentiation, activation and apoptosis.[J]. Basic Research in Cardiology, 2013, 108 3: 350. DOI:10.1007/s00395-013-0350-4
[6] YANNICK WAUMANS. The Dipeptidyl Peptidases 4, 8, and 9 in Mouse Monocytes and Macrophages: DPP8/9 Inhibition Attenuates M1 Macrophage Activation in Mice.[J]. Inflammation, 2016, 39 1: 413-424. DOI:10.1007/s10753-015-0263-5

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