GORALATIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H33N5O9
Molecular Weight	487.5041
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(O)=O

InChI

InChIKey=HJDRXEQUFWLOGJ-AJNGGQMLSA-N

InChI=1S/C20H33N5O9/c1-11(27)22-14(10-26)18(31)24-13(9-16(28)29)17(30)23-12(5-2-3-7-21)19(32)25-8-4-6-15(25)20(33)34/h12-15,26H,2-10,21H2,1H3,(H,22,27)(H,23,30)(H,24,31)(H,28,29)(H,33,34)/t12-,13-,14-,15-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27088094 | https://www.ncbi.nlm.nih.gov/pubmed/1457609

The natural tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP also known as Goralatide) is generated from the N-terminus of thymosin-β4 through enzymatic cleavage by prolyl oligopeptidase (POP). AcSDKP regulation of proliferation of different cells is implicated in hematopoiesis and angiogenesis. This tetrapeptide present in almost all cells was recently detected at elevated concentrations in neoplastic diseases. However, previously reported in vitro and in vivo studies indicate that AcSDKP does not contribute to the pathogenesis of cancers. AcSDKP was in the phase II clinical trial for development of a new non-radioactive test for measuring glomerular filtration rate in patient with Chronic Kidney Disease. In addition, using mice models was concluded ,that AcSDKP might be an oral antifibrotic peptide drug that would be relevant to combating fibroproliferative kidney diseases such as diabetic nephropathy.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
hematopoietic stem cell proliferation 1 Target ID: GO:0071425 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1457609	Modulator 828

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic kidney disease 56 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11532682	Diagnostic		Phase II 1132	Unknown Approved Use Unknown
Diabetic nephropathy 35 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27088094	Primary		Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
110 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7895600	128 nmol/kg single, intramuscular dose: 128 nmol/kg route of administration: Intramuscular experiment type: SINGLE co-administered:		GORALATIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
156 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7895600	128 nmol/kg single, subcutaneous dose: 128 nmol/kg route of administration: Subcutaneous experiment type: SINGLE co-administered:		GORALATIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
117 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7895600	128 nmol/kg single, intravenous dose: 128 nmol/kg route of administration: Intravenous experiment type: SINGLE co-administered:		GORALATIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.5 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7895600	128 nmol/kg single, intravenous dose: 128 nmol/kg route of administration: Intravenous experiment type: SINGLE co-administered:		GORALATIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as perpetrator

Target	Modality	Activity
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=170466626	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=170466626	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=170466626	no

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P008UPZ	https://www.1pchem.com/search?query=1P008UPZ
Alfa Chemistry	46540	http://www.alfa-chemistry.com/search.aspx?q=46540
Alfa Chemistry	ACM120081143	http://www.alfa-chemistry.com/search.aspx?q=ACM120081143
Bachem	H-1156	https://shop.bachem.com/catalogsearch/result/?q=H-1156
eMolecules	50418660	https://orderbb.emolecules.com/search/#?query=50418660

PubMed

Title	Date	PubMed
Therapeutic measures in proteinuric nephropathy.	2005 Dec	16336567
Therapeutic potential of thymosin-beta4 and its derivative N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) in cardiac healing after infarction.	2006	17083265
Signaling by the angiotensin-converting enzyme.	2006 Apr 14	16614314
N-acetyl-seryl-aspartyl-lysyl-proline inhibits DNA synthesis in human mesangial cells via up-regulation of cell cycle modulators.	2006 Apr 14	16497271
N-acetyl-seryl-aspartyl-lysyl-proline ameliorates the progression of renal dysfunction and fibrosis in WKY rats with established anti-glomerular basement membrane nephritis.	2006 Mar	16452498
Anemia and heart failure: a cause of progression or only a consequence?	2007	21977269
Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization.	2007 Jan 11	17108969
Role of N-acetyl-seryl-aspartyl-lysyl-proline in the antifibrotic and anti-inflammatory effects of the angiotensin-converting enzyme inhibitor captopril in hypertension.	2007 Mar	17283252
Erythropoietin stimulating agents in the management of anemia of chronic kidney disease.	2008 Feb 2	19920963
[Anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline in lung of rat with silicosis].	2008 Jul	19080377
Role of paracrine factors in stem and progenitor cell mediated cardiac repair and tissue fibrosis.	2008 Oct 13	19014650
Prevention of aortic fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in angiotensin II-induced hypertension.	2008 Sep	18641275
N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin.	2009 Feb	19098114
[Antifibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline mediated by regulation of transforming growth factor beta and connective tissue growth factor expression on rats with silicosis].	2009 Jul	20039536
Prolyl oligopeptidase is inhibited in relapsing-remitting multiple sclerosis.	2010 Apr 6	20370893
The cardio-renal-anaemia syndrome predicts survival in peritoneally dialyzed patients.	2010 Aug 30	22371797

Patents

Sample Use Guides

In Vivo Use Guide

Once intravenous administration of 100 µg or less

Route of Administration: Intravenous

In Vitro Use Guide

It was shown that exogenous AcSDKP (Goralatide) (10-13 to 10-5M) exerted no effect on the proliferation of actively dividing malignant cells. Using S17092, a specific POP inhibitor (POPi), to suppress the biosynthesis of AcSDKP in U87-MG glioblastoma cells characterized by high intracellular levels of this peptide, it was found, that all tested doses of POPi resulted in an equally effective depletion of AcSDKP, which was not correlated with the dose-dependent decreases in the proliferation rate of treated cells. Interestingly, addition of exogenous AcSDKP markedly reversed the reduction in the proliferation of U87-MG cells treated with the highest dose of POPi, and this effect was associated with activation of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway. However, extracellular-regulated protein kinase (ERK) activation was unaltered by S17092 and AcSDKP co-treatment.

Name

Type

Language

GORALATIDE

Official Name

English

SERASPENIDE

Common Name

English

1-(N(SUP 2)-(N-(N-ACETYL-L-SERYL)-L-.ALPHA.-ASPARTYL)-L-LYSYL)-L-PROLINE

Systematic Name

English

L-PROLINE, N-ACETYL-L-SERYL-L-.ALPHA.-ASPARTYL-L-LYSYL-

Systematic Name

English

goralatide [INN]

Common Name

English

AC-SER-ASP-LYS-PRO

Common Name

English

Code System Code Type Description

ChEMBL

CHEMBL2104460