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

Molecular Formula	C20H33N5O9
Molecular Weight	487.5041
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

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 846

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic kidney disease 55 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11532682	Diagnostic		Phase II 1147	Unknown Approved Use Unknown
Diabetic nephropathy 37 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27088094	Primary		Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
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
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

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 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as perpetrator

Target	Modality	Activity
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=170466626	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=170466626	no
CYP3A4 2633	inhibitor 4027 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
N-acetyl-seryl-aspartyl-lysyl-proline attenuates renal inflammation and tubulointerstitial fibrosis in rats.	2010-12	21042772
Statins inhibit angiotensin II/Smad pathway and related vascular fibrosis, by a TGF-β-independent process.	2010-11-30	21152444
The N domain of human angiotensin-I-converting enzyme: the role of N-glycosylation and the crystal structure in complex with an N domain-specific phosphinic inhibitor, RXP407.	2010-11-12	20826823
[Effect of N-acetyl-seryl-aspartyl-lysyl-proline on regulation of expression of ras-raf-ERK1/2 signal transduction pathway in lung of rats with silicosis].	2010-10	21126429
The cardio-renal-anaemia syndrome predicts survival in peritoneally dialyzed patients.	2010-08-30	22371797
New anti-fibrotic mechanisms of n-acetyl-seryl-aspartyl-lysyl-proline in silicon dioxide-induced silicosis.	2010-08-14	20624403
Captopril reduces cardiac inflammatory markers in spontaneously hypertensive rats by inactivation of NF-kB.	2010-05-12	20462420
Prolyl oligopeptidase is inhibited in relapsing-remitting multiple sclerosis.	2010-04-06	20370893
Myelopoiesis modulation by ACE hyperfunction in kinin B(1) receptor knockout mice: relationship with AcSDKP levels.	2010-03-30	20096676
N-acetyl-seryl-aspartyl-lysyl-proline attenuates renal injury and dysfunction in hypertensive rats with reduced renal mass: council for high blood pressure research.	2010-02	20026760
Prevention of myocardial fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats.	2009-10-26	20310083
[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].	2009-07	20039536
[Role of extracellular signal-regulated kinase 1/2 on inhibition of N-acetyl-seryl-aspartyl-lysyl-proline on proliferation and collagen synthesis of cultured rat pulmonary fibroblasts induced by platelet-derived growth factor].	2009-07	20039534
N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin.	2009-02	19098114
[Antifibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline mediated by the regulation of MCP-1 and ED-1 expression on rats with silicosis].	2008-11	19238998
Role of paracrine factors in stem and progenitor cell mediated cardiac repair and tissue fibrosis.	2008-10-13	19014650
Prevention of aortic fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in angiotensin II-induced hypertension.	2008-09	18641275
[Anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline in lung of rat with silicosis].	2008-07	19080377
Erythropoietin stimulating agents in the management of anemia of chronic kidney disease.	2008-02-02	19920963
Angiotensin converting enzyme inhibitor but not angiotensin receptor blockade or statin ameliorates murine adriamycin nephropathy.	2008-02	18033243
Role of N-acetyl-seryl-aspartyl-lysyl-proline in the antifibrotic and anti-inflammatory effects of the angiotensin-converting enzyme inhibitor captopril in hypertension.	2007-03	17283252
Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization.	2007-01-11	17108969
Anemia and heart failure: a cause of progression or only a consequence?	2007	21977269
Signaling by the angiotensin-converting enzyme.	2006-04-14	16614314
N-acetyl-seryl-aspartyl-lysyl-proline inhibits DNA synthesis in human mesangial cells via up-regulation of cell cycle modulators.	2006-04-14	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.	2006-03	16452498
Therapeutic potential of thymosin-beta4 and its derivative N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) in cardiac healing after infarction.	2006	17083265
Therapeutic measures in proteinuric nephropathy.	2005-12	16336567
Angiotensin-converting enzyme inhibitors: a new mechanism of action.	2005-10-18	16216963
Levels of hematopoiesis inhibitor N-acetyl-seryl-aspartyl-lysyl-proline partially explain the occurrence of anemia in heart failure.	2005-09-20	16172283
N-acetyl-seryl-aspartyl-lysyl-proline prevents renal insufficiency and mesangial matrix expansion in diabetic db/db mice.	2005-03	15734863
N-acetyl-seryl-aspartyl-lysyl-proline stimulates angiogenesis in vitro and in vivo.	2004-11	15256375
Reduction of cardiac fibrosis decreases systolic performance without affecting diastolic function in hypertensive rats.	2004-05	15023934
Ac-SDKP reverses inflammation and fibrosis in rats with heart failure after myocardial infarction.	2004-02	14691195
Local induction of angiotensin-converting enzyme in the kidney as a mechanism of progressive renal diseases.	2003-10	12969129
N-Acetyl-seryl-aspartyl-lysyl-proline inhibits TGF-beta-mediated plasminogen activator inhibitor-1 expression via inhibition of Smad pathway in human mesangial cells.	2003-04	12660320
Angiotensin I-converting enzyme and metabolism of the haematological peptide N-acetyl-seryl-aspartyl-lysyl-proline.	2001-12	11903317
Long-term effect of N-acetyl-seryl-aspartyl-lysyl-proline on left ventricular collagen deposition in rats with 2-kidney, 1-clip hypertension.	2001-06-26	11425781
Effect of N-acetyl-seryl-aspartyl-lysyl-proline on DNA and collagen synthesis in rat cardiac fibroblasts.	2001-03	11244003
Antifibrotic effects of N-acetyl-seryl-aspartyl-Lysyl-proline on the heart and kidney in aldosterone-salt hypertensive rats.	2001-02	11230375

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.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 08:41:09 GMT 2025` Edited by `admin` on `Wed Apr 02 08:41:09 GMT 2025`
Record UNII	H041538E9P
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GORALATIDE

Official Name

English

AC-SER-ASP-LYS-PRO

Preferred 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

Code System Code Type Description

ChEMBL

CHEMBL2104460