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
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
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
Cmax
| 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 |
T1/2
| 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 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Antifibrotic effects of N-acetyl-seryl-aspartyl-Lysyl-proline on the heart and kidney in aldosterone-salt hypertensive rats. | 2001 Feb |
|
| Long-term effect of N-acetyl-seryl-aspartyl-lysyl-proline on left ventricular collagen deposition in rats with 2-kidney, 1-clip hypertension. | 2001 Jun 26 |
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| 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 Apr |
|
| Ac-SDKP reverses inflammation and fibrosis in rats with heart failure after myocardial infarction. | 2004 Feb |
|
| Therapeutic measures in proteinuric nephropathy. | 2005 Dec |
|
| N-acetyl-seryl-aspartyl-lysyl-proline prevents renal insufficiency and mesangial matrix expansion in diabetic db/db mice. | 2005 Mar |
|
| Angiotensin-converting enzyme inhibitors: a new mechanism of action. | 2005 Oct 18 |
|
| Levels of hematopoiesis inhibitor N-acetyl-seryl-aspartyl-lysyl-proline partially explain the occurrence of anemia in heart failure. | 2005 Sep 20 |
|
| Therapeutic potential of thymosin-beta4 and its derivative N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) in cardiac healing after infarction. | 2006 |
|
| Signaling by the angiotensin-converting enzyme. | 2006 Apr 14 |
|
| N-acetyl-seryl-aspartyl-lysyl-proline inhibits DNA synthesis in human mesangial cells via up-regulation of cell cycle modulators. | 2006 Apr 14 |
|
| 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 |
|
| Anemia and heart failure: a cause of progression or only a consequence? | 2007 |
|
| Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization. | 2007 Jan 11 |
|
| 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 |
|
| Angiotensin converting enzyme inhibitor but not angiotensin receptor blockade or statin ameliorates murine adriamycin nephropathy. | 2008 Feb |
|
| Erythropoietin stimulating agents in the management of anemia of chronic kidney disease. | 2008 Feb 2 |
|
| [Anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline in lung of rat with silicosis]. | 2008 Jul |
|
| [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 Nov |
|
| Role of paracrine factors in stem and progenitor cell mediated cardiac repair and tissue fibrosis. | 2008 Oct 13 |
|
| Prevention of aortic fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in angiotensin II-induced hypertension. | 2008 Sep |
|
| N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin. | 2009 Feb |
|
| [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 |
|
| [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 Jul |
|
| New anti-fibrotic mechanisms of n-acetyl-seryl-aspartyl-lysyl-proline in silicon dioxide-induced silicosis. | 2010 Aug 14 |
|
| The cardio-renal-anaemia syndrome predicts survival in peritoneally dialyzed patients. | 2010 Aug 30 |
|
| N-acetyl-seryl-aspartyl-lysyl-proline attenuates renal inflammation and tubulointerstitial fibrosis in rats. | 2010 Dec |
|
| 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 Feb |
|
| Myelopoiesis modulation by ACE hyperfunction in kinin B(1) receptor knockout mice: relationship with AcSDKP levels. | 2010 Mar 30 |
|
| Captopril reduces cardiac inflammatory markers in spontaneously hypertensive rats by inactivation of NF-kB. | 2010 May 12 |
|
| 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 Nov 12 |
|
| Statins inhibit angiotensin II/Smad pathway and related vascular fibrosis, by a TGF-β-independent process. | 2010 Nov 30 |
|
| [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 Oct |
Patents
Sample Use Guides
Once intravenous administration of 100 µg or less
Route of Administration:
Intravenous
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.
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CHEMBL2104460
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65938
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C058504
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7149
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SUB07961MIG
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120081-14-3
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DTXSID0057629
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C170033
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H041538E9P
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100000084257
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ACTIVE MOIETY
