KYP-2047 | CAS# 796874-99-2 | POP, PEP inhibitor

MedKoo Cat#: 522519 | Name: KYP-2047

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

KYP-2047 is a very potent, selective inhibitor of Prolyl oligopeptidase (POP), also known as prolyl endopeptidase (PEP or PE). Ki = .023nM (porcine). KYP-2047 penetrates mouse brain and effectively inhibits mouse prolyl oligopeptidase. KYP-2047 reduces α-synuclein protein levels and aggregates in cellular and animal models of Parkinson's disease.

Chemical Structure

KYP-2047

CAS# 796874-99-2

Theoretical Analysis

MedKoo Cat#: 522519

Name: KYP-2047

CAS#: 796874-99-2

Chemical Formula: C20H25N3O2

Exact Mass: 339.1947

Molecular Weight: 339.44

Elemental Analysis: C, 70.77; H, 7.42; N, 12.38; O, 9.43

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 350.00	2 Weeks
25mg	USD 1,050.00	2 Weeks

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Synonym

KYP-2047; KYP2047; KYP 2047.

IUPAC/Chemical Name

(2S)-1-[[(2S)-1-(1-Oxo-4-phenylbutyl)-2-pyrrolidinyl]carbonyl]-2-pyrrolidinecarbonitrile

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

SMILES Code

N#C[C@H]1N(C([C@H]2N(C(CCCC3=CC=CC=C3)=O)CCC2)=O)CCC1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

KYP-2047 is a very potent, selective inhibitor of Prolyl oligopeptidase (POP).

In vitro activity:

These results demonstrated that KYP-2047 was able to reduce TSCCs cell viability at the concentrations of 50 μM and 100 μM. Additionally, KYP-2047 was able to increase Bax, Bad and caspase-3 expression, whereas Bcl-2 and p53 expression were reduced. Moreover, KYP-2047 significantly reduced vascular-endothelial-growth-factor (VEGF) and endothelial-nitric-oxide-synthase (eNOS) expression. Reference: Oncotarget. 2021 Dec 7;12(25):2459-2473. https://pubmed.ncbi.nlm.nih.gov/34917264/

In vivo activity:

Following PREP inhibition, this study found a decrease in high molecular-weight oligomeric aSyn and a concomitant increase in the amount of the autophagosome marker, LC3BII, suggesting enhanced macroautophagy (autophagy) and aSyn clearance by KYP-2047. Moreover, 28-day treatment with KYP-2047 caused significant increases in striatal dopamine levels. In cell culture, overexpression of PREP reduced the autophagy. Reference: Neurobiol Dis. 2014 Aug;68:1-15. https://pubmed.ncbi.nlm.nih.gov/24746855/

	Solvent	mg/mL	mM
Solubility
	Ethanol	17.0	50.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 339.44 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Scuderi SA, Casili G, Filippone A, Lanza M, Basilotta R, Giuffrida R, Munaò S, Colarossi L, Capra AP, Esposito E, Paterniti I. Beneficial effect of KYP-2047, a propyl-oligopeptidase inhibitor, on oral squamous cell carcinoma. Oncotarget. 2021 Dec 7;12(25):2459-2473. doi: 10.18632/oncotarget.28147. PMID: 34917264; PMCID: PMC8664393. 2. Scuderi SA, Casili G, Ardizzone A, Forte S, Colarossi L, Sava S, Paterniti I, Esposito E, Cuzzocrea S, Campolo M. KYP-2047, an Inhibitor of Prolyl-Oligopeptidase, Reduces GlioBlastoma Proliferation through Angiogenesis and Apoptosis Modulation. Cancers (Basel). 2021 Jul 9;13(14):3444. doi: 10.3390/cancers13143444. PMID: 34298658; PMCID: PMC8306782. 3. Savolainen MH, Richie CT, Harvey BK, Männistö PT, Maguire-Zeiss KA, Myöhänen TT. The beneficial effect of a prolyl oligopeptidase inhibitor, KYP-2047, on alpha-synuclein clearance and autophagy in A30P transgenic mouse. Neurobiol Dis. 2014 Aug;68:1-15. doi: 10.1016/j.nbd.2014.04.003. Epub 2014 Apr 16. PMID: 24746855; PMCID: PMC7254878. 4. Jalkanen AJ, Leikas JV, Forsberg MM. KYP-2047 penetrates mouse brain and effectively inhibits mouse prolyl oligopeptidase. Basic Clin Pharmacol Toxicol. 2014 Jun;114(6):460-3. doi: 10.1111/bcpt.12184. Epub 2014 Jan 25. PMID: 24350801.

In vitro protocol:

In vivo protocol:

1. Savolainen MH, Richie CT, Harvey BK, Männistö PT, Maguire-Zeiss KA, Myöhänen TT. The beneficial effect of a prolyl oligopeptidase inhibitor, KYP-2047, on alpha-synuclein clearance and autophagy in A30P transgenic mouse. Neurobiol Dis. 2014 Aug;68:1-15. doi: 10.1016/j.nbd.2014.04.003. Epub 2014 Apr 16. PMID: 24746855; PMCID: PMC7254878. 2. Jalkanen AJ, Leikas JV, Forsberg MM. KYP-2047 penetrates mouse brain and effectively inhibits mouse prolyl oligopeptidase. Basic Clin Pharmacol Toxicol. 2014 Jun;114(6):460-3. doi: 10.1111/bcpt.12184. Epub 2014 Jan 25. PMID: 24350801.

1: Savolainen MH, Richie CT, Harvey BK, Männistö PT, Maguire-Zeiss KA, Myöhänen TT. The beneficial effect of a prolyl oligopeptidase inhibitor, KYP-2047, on alpha-synuclein clearance and autophagy in A30P transgenic mouse. Neurobiol Dis. 2014 Aug;68:1-15. doi: 10.1016/j.nbd.2014.04.003. PubMed PMID: 24746855. 2: Jalkanen AJ, Leikas JV, Forsberg MM. KYP-2047 penetrates mouse brain and effectively inhibits mouse prolyl oligopeptidase. Basic Clin Pharmacol Toxicol. 2014 Jun;114(6):460-3. doi: 10.1111/bcpt.12184. PubMed PMID: 24350801. 3: Jalkanen AJ, Hakkarainen JJ, Lehtonen M, Venäläinen T, Kääriäinen TM, Jarho E, Suhonen M, Forsberg MM. Brain pharmacokinetics of two prolyl oligopeptidase inhibitors, JTP-4819 and KYP-2047, in the rat. Basic Clin Pharmacol Toxicol. 2011 Dec;109(6):443-51. doi: 10.1111/j.1742-7843.2011.00747.x. PubMed PMID: 21707925. 4: Myöhänen TT, Hannula MJ, Van Elzen R, Gerard M, Van Der Veken P, García-Horsman JA, Baekelandt V, Männistö PT, Lambeir AM. A prolyl oligopeptidase inhibitor, KYP-2047, reduces α-synuclein protein levels and aggregates in cellular and animal models of Parkinson's disease. Br J Pharmacol. 2012 Jun;166(3):1097-113. doi: 10.1111/j.1476-5381.2012.01846.x. PubMed PMID: 22233220; PubMed Central PMCID: PMC3417432. 5: Jalkanen AJ, Savolainen K, Forsberg MM. Inhibition of prolyl oligopeptidase by KYP-2047 fails to increase the extracellular neurotensin and substance P levels in rat striatum. Neurosci Lett. 2011 Sep 15;502(2):107-11. doi: 10.1016/j.neulet.2011.07.033. PubMed PMID: 21820035. 6: Jalkanen AJ, Leikas JV, Forsberg MM. Prolyl oligopeptidase inhibition decreases extracellular acetylcholine levels in rat hippocampus and prefrontal cortex. Neurosci Lett. 2014 Sep 5;579:110-3. doi: 10.1016/j.neulet.2014.07.026. PubMed PMID: 25064702. 7: Savolainen MH, Yan X, Myöhänen TT, Huttunen HJ. Prolyl oligopeptidase enhances α-synuclein dimerization via direct protein-protein interaction. J Biol Chem. 2015 Feb 20;290(8):5117-26. doi: 10.1074/jbc.M114.592931. PubMed PMID: 25555914; PubMed Central PMCID: PMC4335246. 8: Jalkanen AJ, Piepponen TP, Hakkarainen JJ, De Meester I, Lambeir AM, Forsberg MM. The effect of prolyl oligopeptidase inhibition on extracellular acetylcholine and dopamine levels in the rat striatum. Neurochem Int. 2012 Feb;60(3):301-9. doi: 10.1016/j.neuint.2011.12.010. PubMed PMID: 22210165. 9: Peltonen I, Jalkanen AJ, Sinervä V, Puttonen KA, Männistö PT. Different effects of scopolamine and inhibition of prolyl oligopeptidase on mnemonic and motility functions of young and 8- to 9-month-old rats in the radial-arm maze. Basic Clin Pharmacol Toxicol. 2010 Apr;106(4):280-7. doi: 10.1111/j.1742-7843.2009.00484.x. PubMed PMID: 20041878. 10: Dokleja L, Hannula MJ, Myöhänen TT. Inhibition of prolyl oligopeptidase increases the survival of alpha-synuclein overexpressing cells after rotenone exposure by reducing alpha-synuclein oligomers. Neurosci Lett. 2014 Nov 7;583:37-42. doi: 10.1016/j.neulet.2014.09.026. PubMed PMID: 25240592. 11: Tenorio-Laranga J, Männistö PT, Storvik M, Van der Veken P, García-Horsman JA. Four day inhibition of prolyl oligopeptidase causes significant changes in the peptidome of rat brain, liver and kidney. Biochimie. 2012 Sep;94(9):1849-59. doi: 10.1016/j.biochi.2012.04.005. PubMed PMID: 22546504. 12: Myöhänen TT, Tenorio-Laranga J, Jokinen B, Vázquez-Sánchez R, Moreno-Baylach MJ, García-Horsman JA, Männistö PT. Prolyl oligopeptidase induces angiogenesis both in vitro and in vivo in a novel regulatory manner. Br J Pharmacol. 2011 Aug;163(8):1666-78. doi: 10.1111/j.1476-5381.2010.01146.x. PubMed PMID: 21133893; PubMed Central PMCID: PMC3166694. 13: Svarcbahs R, Julku UH, Myöhänen TT. Inhibition of Prolyl Oligopeptidase Restores Spontaneous Motor Behavior in the α-Synuclein Virus Vector-Based Parkinson's Disease Mouse Model by Decreasing α-Synuclein Oligomeric Species in Mouse Brain. J Neurosci. 2016 Dec 7;36(49):12485-12497. PubMed PMID: 27927963. 14: Myöhänen TT, Norrbacka S, Savolainen MH. Prolyl oligopeptidase inhibition attenuates the toxicity of a proteasomal inhibitor, lactacystin, in the alpha-synuclein overexpressing cell culture. Neurosci Lett. 2017 Jan 1;636:83-89. doi: 10.1016/j.neulet.2016.11.008. PubMed PMID: 27818354. 15: Jalkanen AJ, Puttonen KA, Venäläinen JI, Sinervä V, Mannila A, Ruotsalainen S, Jarho EM, Wallén EA, Männistö PT. 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. PubMed PMID: 17244263. 16: Peltonen I, Myöhänen TT, Männistö PT. Different interactions of prolyl oligopeptidase and neurotensin in dopaminergic function of the rat nigrostriatal and mesolimbic pathways. Neurochem Res. 2012 Sep;37(9):2033-41. doi: 10.1007/s11064-012-0825-y. PubMed PMID: 22729983. 17: Klimaviciusa L, Jain RK, Jaako K, Van Elzen R, Gerard M, van Der Veken P, Lambeir AM, Zharkovsky A. In situ prolyl oligopeptidase activity assay in neural cell cultures. J Neurosci Methods. 2012 Feb 15;204(1):104-10. doi: 10.1016/j.jneumeth.2011.11.011. PubMed PMID: 22101193. 18: Kallinen A, Todorov B, Kallionpää R, Bäck S, Sarparanta M, Raki M, García-Horsman JA, Bergström KA, Wallén EA, Männistö PT, Airaksinen AJ. Synthesis and biological evaluation of novel (123)I-labeled 4-(4-iodophenyl)butanoyl-L-prolyl-(2S)-pyrrolidines for imaging prolyl oligopeptidase in vivo. Eur J Med Chem. 2014 May 22;79:436-45. doi: 10.1016/j.ejmech.2014.04.014. PubMed PMID: 24763264.