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| Targets |
KYP-2047 targets prolyl oligopeptidase (POP/PREP), a serine protease that cleaves peptide bonds on the carboxyl side of proline residues. POP is involved in the regulation of several neuropeptides and hormones, and its activity has been implicated in neurodegenerative diseases such as Parkinson's disease, as well as in cancer progression. By inhibiting POP with extremely high affinity (Ki = 0.023 nM), KYP-2047 prevents the cleavage of its substrates, leading to altered neuropeptide levels and downstream effects.
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| 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].
In vitro, KYP-2047 is a very potent and selective inhibitor of POP. Its Ki of 0.023 nM for porcine POP indicates femtomolar affinity. In neuronal cells, KYP-2047 clears α-synuclein aggregates induced by oxidative stress. It also reduces glioblastoma proliferation through the regulation of angiogenesis and apoptosis. The compound inhibits the formation of AcSDKP from its precursor thymosin β4. These in vitro activities confirm its potential as a therapeutic agent for neurodegenerative diseases and cancer. |
| 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].
In vivo, KYP-2047 has been shown to reduce α-synuclein protein levels and aggregates in cellular and animal models of Parkinson's disease. Its ability to cross the blood-brain barrier (BBB) is a key feature for its application in central nervous system disorders. The compound's potent inhibition of POP in the brain can modulate neuropeptide levels and potentially alleviate symptoms of neurodegeneration. |
| Enzyme Assay |
Non-cell-based enzyme assays for KYP-2047 typically involve in vitro POP activity assays using purified recombinant POP enzyme. The compound is incubated with the enzyme and a fluorogenic substrate (e.g., Z-Gly-Pro-AMC) at varying concentrations. POP activity is measured by monitoring the release of free AMC (7-amino-4-methylcoumarin) using fluorescence spectroscopy. The Ki of 0.023 nM is determined from dose-response curves using appropriate kinetic models. Selectivity profiling against other proteases is performed to confirm specificity.
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| 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. Cellular assays for KYP-2047 are performed using neuronal cell lines, such as SH-SY5Y cells, to study its effects on α-synuclein aggregation. Cells are treated with the compound and then exposed to oxidative stress to induce α-synuclein aggregation. The number of cells with α-synuclein inclusions and the colocalization of α-synuclein and PREP are assessed. Glioblastoma cell lines are used to study the compound's effects on proliferation, angiogenesis, and apoptosis. |
| Animal Protocol |
In vivo animal models for KYP-2047 include models of Parkinson's disease, such as the MPTP or 6-OHDA models in mice or rats. The compound is administered via appropriate routes (e.g., intraperitoneal or oral), and its effects on α-synuclein levels, dopaminergic neuron survival, and behavioral outcomes are assessed. The compound's ability to cross the BBB is confirmed by measuring its concentration in brain tissue.
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| ADME/Pharmacokinetics |
KYP-2047 has a molecular weight of 401.50 g/mol and a molecular formula of C₂₃H₂₃N₃O₃. Its CAS number is 796874-99-2. The compound is supplied as a solid with a purity of ≥95%. It is soluble in DMSO. Storage conditions: -20°C. The compound is a potent and BBB-penetrating POP inhibitor. Detailed pharmacokinetic parameters such as half-life and bioavailability are not extensively reported.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for KYP-2047 are not extensively reported in the available literature. As a research compound, its safety profile would need to be established through standard preclinical toxicity assessments. The compound is intended for research use only and is not for human consumption. Standard laboratory safety precautions should be followed when handling the compound.
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| References |
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| Additional Infomation |
KYP-2047 is a very potent, selective, and BBB-penetrant prolyl oligopeptidase (POP) inhibitor with a Ki of 0.023 nM. It clears α-synuclein aggregates induced by oxidative stress in neuronal cells and reduces glioblastoma proliferation through angiogenesis and apoptosis regulation. It inhibits the formation of AcSDKP from thymosin β4. KYP-2047 is used in research for Parkinson's disease and cancer. Its CAS number is 796874-99-2.
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| Molecular Formula |
C20H25N3O2
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| Molecular Weight |
339.431404829025
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| Exact Mass |
339.194
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| CAS # |
796874-99-2
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| PubChem CID |
11198569
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| Appearance |
White to off-white solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
25
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| Complexity |
532
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C(N1CCC[C@H]1C#N)([C@@H]1CCCN1C(=O)CCCC1C=CC=CC=1)=O
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| InChi Key |
SPXFAUXQZWJGCJ-ROUUACIJSA-N
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| 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
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| Chemical Name |
(2S)-1-[(2S)-1-(4-phenylbutanoyl)pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile
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| Synonyms |
KYP 2047; KYP2047; KYP-2047
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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