DBPR108 is a novel, potent, selective, and orally bioavailable dipeptide-derived inhibitor of DPP4 with IC50 of 15 nM; It shows no inhibition on DDP8 and DPP9. The in vivo effects of DBPR108, including inhibition of plasma DPP-IV activity and suppression of blood glucose elevation, were also demonstrated. As a potent, selective, long-acting and safe DPP-IV inhibitor, DBPR108 has the potential to be developed as a therapeutic for the treatment of type 2 diabetes mellitus.

Physicochemical Properties

Molecular Formula	C16H25FN4O2
Molecular Weight	324.39
Exact Mass	324.196
CAS #	1186426-66-3
Related CAS #	1186426-66-3
PubChem CID	44201003
Appearance	White to off-white solid powder
LogP	1.096
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	23
Complexity	508
Defined Atom Stereocenter Count	2
SMILES	CC(C)(CC(=O)N1CCCC1)NCC(=O)N2C[C@H](C[C@H]2C#N)F
InChi Key	VQKSCYBKUIDZEI-STQMWFEESA-N
InChi Code	InChI=1S/C16H25FN4O2/c1-16(2,8-14(22)20-5-3-4-6-20)19-10-15(23)21-11-12(17)7-13(21)9-18/h12-13,19H,3-8,10-11H2,1-2H3/t12-,13-/m0/s1
Chemical Name	(2S,4S)-4-fluoro-1-[2-[(2-methyl-4-oxo-4-pyrrolidin-1-ylbutan-2-yl)amino]acetyl]pyrrolidine-2-carbonitrile
Synonyms	DBPR-108; DBPR108; DBPR 108
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In vitro activity: DBPR108 is a novel, potent, selective, and orally bioavailable dipeptide-derived inhibitor of DPP4 with IC50 of 15 nM; It shows no inhibition on DDP8 and DPP9. The in vivo effects of DBPR108, including inhibition of plasma DPP-IV activity and suppression of blood glucose elevation, were also demonstrated. As a potent, selective, long-acting and safe DPP-IV inhibitor, DBPR108 has the potential to be developed as a therapeutic for the treatment of type 2 diabetes mellitus. Kinase Assay: DBPR108 is a novel, potent, selective, and orally bioavailable dipeptide-derived inhibitor of DPP4 with IC50 of 15 nM; It shows no inhibition on DDP8 and DPP9. Cell Assay:
ln Vivo	The in vivo effects of DBPR108, including inhibition of plasma DPP-IV activity and suppression of blood glucose elevation, were also demonstrated. DBPR108 is a potent, selective, long-acting and safe DPP-IV inhibitor as a potential treatment of type 2 diabetes mellitus.
Animal Protocol
References	[1]. (2S,4S)-1-[2-(1,1-dimethyl-3-oxo-3-pyrrolidin-1-yl-propylamino)acetyl]-4-fluoro-pyrrolidine-2-carbonitrile: a potent, selective, and orally bioavailable dipeptide-derived inhibitor of dipeptidyl peptidase IV. Bioorg Med Chem Lett. 2010 Jun.

Solubility Data

Solubility (In Vitro)

DMSO:10 mM in DMSO Water:<1 mg/mL Ethanol:

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (7.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.0827 mL	15.4135 mL	30.8271 mL
	5 mM	0.6165 mL	3.0827 mL	6.1654 mL
	10 mM	0.3083 mL	1.5414 mL	3.0827 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.