KYP-2047 is a potent BBB (blood-brain barrier) permeable/penetrable prolyl oligopeptidase (POP) inhibitor (antagonist) with Ki of 0.023 nM. KYP-2047 reduces glioblastoma proliferation through angiogenesis and apoptosis regulation.

Physicochemical Properties

Molecular Formula	C20H25N3O2
Molecular Weight	339.431404829025
Exact Mass	339.194
CAS #	796874-99-2
PubChem CID	11198569
Appearance	White to off-white solid powder
LogP	2.3
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	5
Heavy Atom Count	25
Complexity	532
Defined Atom Stereocenter Count	2
SMILES	C(N1CCC[C@H]1C#N)([C@@H]1CCCN1C(=O)CCCC1C=CC=CC=1)=O
InChi Key	SPXFAUXQZWJGCJ-ROUUACIJSA-N
InChi Code	InChI=1S/C20H25N3O2/c21-15-17-10-5-13-22(17)20(25)18-11-6-14-23(18)19(24)12-4-9-16-7-2-1-3-8-16/h1-3,7-8,17-18H,4-6,9-14H2/t17-,18-/m0/s1
Chemical Name	(2S)-1-[(2S)-1-(4-phenylbutanoyl)pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile
Synonyms	KYP 2047; KYP2047; KYP-2047
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	The concentration-dependent reduction of U-87, U-138, and A-172 cell viability is observed with KYP-2047 (0-100 μM) [2]. KYP-2047 (0-100 μM) drastically lowers the expression of TGF-β and enhances the production of the pro-apoptotic proteins Bax, p53, and caspase-3, while lowering the expression of Bcl-2 [2].
ln Vivo	In the water maze, KYP-2047 (1 or 5 mg/kg, 30 min before daily testing) dose-dependently enhanced escape performance (i.e., latency to discover the concealed platform and swimming path length) in young but not elderly rats. 1. The hypothalamus's neurotensin concentrations are raised by KYP-2047 (9 or 27 μmol/kg; IP); once, one, or three hours prior to beheading; twice daily for ten days [1]. Tumor mass and neutrophil infiltration are markedly decreased by KYP-2047 (0–5 mg/kg) [2]. The expression of vascular endothelial growth factor (VEGF), CD34, angiopoietin (Ang), and endothelial nitric oxide synthase (eNOS) is dramatically reduced by KYP-2047 (0–5 mg/kg) [2].
Cell Assay	Cell Proliferation Assay Cell Types: U-87, U-138 and A-172 cells [2] Tested Concentrations: 0.01 μM, 0.1 μM, 0.5 μM, 1 μM, 10 μM, 30 μM, 50 μM and 100 μM Incubation Duration: 24 h Experimental Results: U-87, U-138 and A-172 cell viability diminished in a concentration-dependent manner. Western Blot Analysis Cell Types: U-87 cells [2] Tested Concentrations: 0, 50, 100 μM Incubation Duration: 24 h Experimental Results: The expression of pro-apoptotic proteins Bax, p53 and cleaved-caspase-3 increased, and the expression of Bcl2 Dramatically diminished. Reduces Ang1 and Ang2 expression, and reduces Ki-67 expression.
References	[1]. Beneficial effect of prolyl oligopeptidase inhibition on spatial memory in young but not in old scopolamine-treated rats. Basic Clin Pharmacol Toxicol. 2007 Feb;100(2):132-8. [2]. KYP-2047, an Inhibitor of Prolyl-Oligopeptidase, Reduces GlioBlastoma Proliferation through Angiogenesis and Apoptosis Modulation. Cancers (Basel). 2021 Jul 9;13(14):3444.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.9461 mL	14.7306 mL	29.4612 mL
	5 mM	0.5892 mL	2.9461 mL	5.8922 mL
	10 mM	0.2946 mL	1.4731 mL	2.9461 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.