Cenupatide
Based on 1 Customer Validation
Cenupatide (UPARANT) is a uPAR and FPR antagonist with anti-angiogenic, anti-inflammatory, and vascular barrier regulatory activities, as well as high stability and resistance to enzymatic degradation in blood/plasma. Cenupatide blocks the uPAR-FPR interaction, reduces VEGF-induced phosphorylation levels of AKT, VEGFR-2, STAT3, JNK, p38 MAPK, ERK1/2, and NF-κB p65, and inhibits αvβ3 integrin activation. Cenupatide suppresses endothelial cell migration, invasion, tube formation, and angiogenic signaling pathways, restores tight junctions and blood-retinal barrier integrity, reduces pro-inflammatory marker levels, and inhibits apoptosis. Cenupatide reduces retinal neovascularization, renal fibrosis, and vascular leakage, and restores visual function in preclinical models. Cenupatide is applicable to research related to retinopathy, diabetic complications, ocular diseases, cancer, and inflammatory diseases.
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- Reinheit: 99.94%
- CAS. Nr.: 1006388-38-0
- Formel: C28H47N11O5
- Molecular Weight:617.74
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Speicherung:
Sealed storage, away from moisture.
Powder -80°C, 2 years , -20°C, 1 year* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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Biologische Aktivität
|
uPAR |
FPR |
ERK1 |
ERK2 |
Akt |
VEGFR2 |
STAT3 |
JNK |
p38 MAPK |
NF-κB |
p65 |
αvβ3 |
Cenupatide (UPARANT) (1-100 nM; 24-72 h) does not affect viability or proliferation of primary human retinal endothelial cells, either alone or when co-treated with VEGF-A[1].
Cenupatide (10-100 nM; 24 h) significantly reduces VEGF-A-induced migration of primary human retinal endothelial cells by ~30% after 24 hours, while having no effect on migration alone[1].
Cenupatide (10 nM; 24 h) reduces VEGF-A-induced invasion of primary human retinal endothelial cells by 40% after 24 hours of incubation[1].
Cenupatide (10 nM; 6 h) reduces VEGF-A-stimulated tube formation of primary human retinal endothelial cells by 50.4% in branching points after 6 hours of incubation[1].
Cenupatide (10-100 nM; 24-72 h) completely prevents VEGF-A-induced loss of transendothelial electrical resistance in confluent primary human retinal endothelial cells over 72 hours, while 1 nM provides partial protection[1].
Cenupatide (10 nM; 72 h) prevents VEGF-A-induced reduction in tight junction protein expression in primary human retinal endothelial cells after 72 hours of incubation[1].
Cenupatide (10 nM; 30 min preincubation prior to 5-60 min VEGF-A stimulation) inhibits VEGF-A-induced VEGFR-2 phosphorylation in primary human retinal endothelial cells by 37.5% at 5 minutes and restores levels to control by 30 minutes, without altering total VEGFR-2 protein or mRNA expression[1].
Cenupatide (10 nM; 24 h for protein analysis; 30 min preincubation prior to 1-4 h VEGF-A stimulation for mRNA analysis) reduces VEGF-A-induced autocrine VEGF-A protein expression by 64% after 24 hours and reduces VEGF-A mRNA expression by up to 77% after 4 hours in primary human retinal endothelial cells[1].
Cenupatide (10 nM; 30 min preincubation prior to 5-60 min VEGF-A stimulation) inhibits VEGF-A-induced phosphorylation of AKT, JNK, p38, and ERK 1/2 in primary human retinal endothelial cells, completely preventing JNK and p38 activation at 5 minutes and returning all four protein phosphorylation levels to near baseline by 30 to 60 minutes[1].
Cenupatide (10 nM; 30 min preincubation prior to 5-60 min VEGF-A stimulation for STAT3 analysis; 30 min preincubation prior to 1-4 h VEGF-A stimulation for HIF-1α analysis) prevents VEGF-A-induced STAT3 phosphorylation and increases HIF-1α mRNA expression in primary human retinal endothelial cells, maintaining STAT3 activation near control levels and restoring HIF-1α mRNA to control levels by 1 hour[1].
Cenupatide (0.001-1 nM; 24 h) dose-dependently inhibits PDR vitreous fluid-induced sprouting in HUVEC spheroids, with maximum inhibition of ~72% at 0.1 nM[2].
Cenupatide (10 nM; 30 minutes) at 10 nM prevents VEGF-induced cytoskeletal reorganization and αvβ3 integrin redistribution to focal adhesions in HUVEC[8].
Cenupatide (10 nM; 4 hours) at 10 nmol/L inhibits VEGF adhesion to vitronectin, both in basal conditions and in the presence of VEGF[8].
Cenupatide (10 aM-10 μM; 4 hours) inhibits VEGF-dependent migration of HUVEC in a dose-dependent manner, with activity starting at femtomolar concentrations[8].
Cenupatide (10 fM-10 μM; 6 hours) potently inhibits VEGF-dependent tube formation in HUVEC, with a 100-fold lower IC50 than RERF and 75% inhibition at 10 nM[8].
Cenupatide (0.15 mM; 60 min) is not inhibited in binding or internalization by PDR vitreous fluid in cultured HUVECs[2].
Cenupatide shows high resistance to chymotrypsin digestion (no detectable breakdown over 60 minutes) and reduced susceptibility to trypsin digestion compared to unmodified peptides, with a trypsin T1/2 of 11.4 minutes at a 10:1 peptide:enzyme ratio with 0.6 mg/L trypsin[8].
Cenupatide (100 nM; 60 minutes) competes with fMLF for binding to FPR on HUVEC, effectively reducing fluorescent fMLF receptor binding when used at 100 nM[8].
Cenupatide (100 nM; 30 minutes) inhibits agonist-dependent FPR internalization in HUVEC when used at 100 nM, while causing minimal internalization of its own fluorescently labeled form[8].
Cenupatide (10 nM; 5-60 minutes) at 10 nM inhibits VEGF-induced phosphorylation of Akt and ERK1/2 in HUVEC[8].
Cenupatide (10 nM,-10 μM; 24-72 hours) at concentrations up to 10 μM does not affect the viability or proliferation of VEGF-stimulated HUVEC over 72 hours[8].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Primary human retinal endothelial cells
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Concentration:1 nM; 10 nM; 100 nM
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Incubation Time:24 h; 48 h; 72 h
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Result:Whether used alone or in combination with VEGF-A, did not affect the viability or proliferation of primary human retinal endothelial cells.
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Cell Line:Primary human retinal endothelial cells
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Concentration:10 nM; 100 nM
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Incubation Time:24 h
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Result:Significantly reduced VEGF-A-induced migration of primary human retinal endothelial cells, with migration decreasing by approximately 30% after 24 hours, whereas it had no effect on cell migration when administered alone.
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Cell Line:Primary human retinal endothelial cells
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Concentration:10 nM
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Incubation Time:24 h
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Result:Reduced the invasion rate of VEGF-A-induced primary human retinal endothelial cells by 40% after 24 hours of incubation.
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Cell Line:Primary human retinal endothelial cells
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Concentration:10 nM
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Incubation Time:72 h; 30 min preincubation prior to 5-60 min VEGF-A stimulation
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Result:Inhibited the VEGF-A-induced downregulation of tight junction protein expression in primary human retinal endothelial cells after 72 hours of incubation.
Inhibited VEGF-A-induced VEGFR-2 phosphorylation: the inhibition rate reached 37.5% at 5 minutes, and phosphorylation levels returned to those of the control group by 30 minutes, without altering total VEGFR-2 protein or mRNA expression.
Inhibited VEGF-A-induced phosphorylation of AKT, JNK, p38, and ERK 1/2; completely blocked JNK and p38 activation at 5 minutes; and restored the phosphorylation levels of these four proteins to near-baseline levels between 30 and 60 minutes.
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Cell Line:Human umbilical vein endothelial cells (HUVEC)
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Concentration:10 aM-10 μM
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Incubation Time:4 hours
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Result:Inhibited VEGF-directed HUVEC migration in a dose-dependent manner, with inhibition starting in the low femtomolar range and plateauing in the nanomolar range.
Reduced VEGF-dependent migration by over 60% at the highest tested concentrations.
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Cell Line:Human umbilical vein endothelial cells (HUVEC)
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Concentration:10 nM
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Incubation Time:5, 10, 15, 60 minutes
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Result:Consistently decreased VEGF-induced, time-dependent phosphorylation of Akt and ERK1/2 in HUVEC.
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Cell Line:Human umbilical vein endothelial cells (HUVEC)
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Concentration:10 nM-10 μM
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Incubation Time:24, 48, 72 hours
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Result:Did not modify VEGF-induced HUVEC growth over 72 hours, as measured by MTS absorbance and xCELLigence cell index, at both 10 nmol/L and 10 μmol/L.
Cenupatide (7 mg/kg; s.c.; three times weekly) prevents diabetic retinal complications and reduces ocular vascular leakage in genetically modified fat rats[3].
Cenupatide (75-150 μg/kg; subcutaneous; single dose) dose-dependently inhibits VEGF-induced angiogenesis in a murine Matrigel sponge assay, reducing vascularization by up to 72% at the 150 μg/kg dose[8].
Cenupatide (5 μg per pellet; subcorneal; single sustained-release dose) completely prevents VEGF-induced corneal neovascularization in rabbits, reducing angiogenic activity by 75% at the 5 μg per pellet dose[8].
Cenupatide (7 mg/kg; s.c.; three times a week) prevents diabetic retinal complications and restores blood-retinal barrier function in genetically diabetic Torii rats[9].
Cenupatide (7.6 g/L; intravitreal; 3 injections on days 4, 8, 12; 1 μL per injection) normalizes iris macro- and microvascular density, FPR1 expression, inflammatory and extracellular matrix degradation marker levels, and CREB/NFκB phosphorylation to non-induced control levels in a mouse model of rubeosis iridis[4].
Cenupatide (15.2 mg/kg; subcutaneous; daily; 5 days from day 4 through day 8) normalizes iris vascular density, FPR1 expression, and inflammatory and extracellular matrix degradation marker levels to non-induced control levels in a mouse model of rubeosis iridis[4].
Cenupatide (1-8 mg/kg; s.c.; daily; 5 days) significantly ameliorates Streptozotocin (HY-13753)-induced diabetic nephropathy in male Sprague-Dawley rats by normalizing uPA activity, αvβ3 integrin/Rac-1 signaling, renal fibrosis, vascular permeability, inflammatory markers, renal function parameters, and glomerular morphology[5].
Cenupatide (4-20 mg/kg; s.c.; daily for 3 days; daily for 5 days; daily for 7 days; single dose) restores retinal ERG function, BRB integrity, and normalizes inflammatory/proangiogenic marker levels in rats with streptozotocin-induced diabetic retinopathy, with ERG recovery lasting ~2 weeks post-treatment; higher and lower/different duration doses lack efficacy or serve safety/Pharmacokinetic profiling[6].
Cenupatide (20 mg/kg; s.c.; single dose) rapidly distributes to plasma, eye, and retina in healthy rats, with detectable levels persisting for at least 24 hours post-dose[6].
Cenupatide (6-24 mg/kg; i.p.; single dose) with single intraperitoneal administration at 12 and 24 mg/kg significantly reduces Carrageenan (HY-125474)-induced paw oedema in male CD-1 mice in both early and late inflammatory phases, while the 6 mg/kg dose shows no significant effect[10].
Cenupatide (12-24 mg/kg; i.p.; 5 total doses) with repeated intraperitoneal administration at 12 and 24 mg/kg dose-dependently abolishes the late phase of carrageenan-induced paw oedema in male CD-1 mice[10].
Cenupatide (7 mg/kg; s.c.; 3 times a week; 19 weeks) prevents retinal impairment in spontaneously diabetic Torii rats, maintaining ERG function, BRB integrity, and retinal cell viability, while reducing proangiogenic and inflammatory marker levels, with a key effect of normalizing uPAR/FPR expression and downstream transcription factor activation in this type 2 diabetic retinopathy model[7].
Cenupatide (8 mg/kg; s.c.; daily; 5 days) reduces activation of proinflammatory transcription factors in streptozotocin-induced diabetic rats with type 1 diabetic retinopathy, without altering uPAR/FPR system expression[7].
Cenupatide (12-24 mg/kg; i.p.; single administration) reduces inflammatory mediator overproduction in rodent models of acute inflammation[9].
Cenupatide (8 mg/kg; s.c.; daily; 5 days) restores renal vascular integrity and modulates aquaporin-2 expression in streptozotocin-induced diabetic nephropathy in Sprague-Dawley rats[9].
Cenupatide (16 mg/kg; s.c.; daily; postnatal day 10 to postnatal day 30) limits retinal cell apoptosis in a rodent model of retinitis pigmentosa[9].
Cenupatide (6-24 mg/kg; i.p.; single dose) with single intraperitoneal administration at 12 and 24 mg/kg significantly reduces carrageenan-induced paw oedema, as well as iNOS, COX-2, and NOx levels in male Wistar rats, while the 6 mg/kg dose shows no significant effect[10].
Cenupatide (6-24 mg/kg; i.p.; single dose) with single intraperitoneal administration at 12 and 24 mg/kg significantly reduces inflammatory cell influx and NOx production in Zymosan (Zymosan A) (HY-W250113)-induced peritonitis in male CD-1 mice, while the 6 mg/kg dose only significantly reduces NOx levels[10].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (mixed gender, postnatal day 7 pups, oxygen-induced retinopathy model)[2]
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Dosage:0.0015 μg/μL; 0.015 μg/μL; 0.15 μg/μL; 1.5 μg/μL
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Administration:intravitreal; at postnatal day 12 and 15
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Result:Showed no effect on neovascular tuft area, VEGF levels, VEGFR-2 phosphorylation, HIF-1α accumulation, or STAT3 phosphorylation at 0.0015 μg/μL.
Reduced neovascular tuft area by ~62% (P < 0.001), reduced VEGFR-2 phosphorylation by ~32% (P < 0.01), and showed no effect on VEGF levels, HIF-1α accumulation, or STAT3 phosphorylation at 0.015 μg/μL.
Reduced neovascular tuft area by ~75% (P < 0.001), reduced VEGF levels by ~49% (P < 0.01), reduced VEGFR-2 phosphorylation by ~52% (P < 0.001), reduced HIF-1α accumulation by ~50% (P < 0.01), and reduced STAT3 phosphorylation by ~49% (P < 0.01) at 0.15 μg/μL.
Reduced neovascular tuft area by ~85% (P < 0.0001), reduced VEGF levels by ~63% (P < 0.001), reduced VEGFR-2 phosphorylation by ~78% (P < 0.001), reduced HIF-1α accumulation by ~82% (P < 0.001), reduced STAT3 phosphorylation by ~84% (P < 0.001), restored occludin and albumin levels to control values to reduce blood-retinal barrier leakage, increased a-wave, b-wave, and sum oscillatory potential amplitudes in electroretinography to improve visual function, reduced TNF-α mRNA by ~38% (P < 0.01), IL-1β mRNA by ~48% (P < 0.001), IL-6 mRNA by ~66% (P < 0.01), iNOS mRNA by ~50% (P < 0.05), ICAM-1 mRNA by ~41% (P < 0.001), and GFAP mRNA by ~83% (P < 0.001), and showed no effect on Bax/Bcl-2 ratio, cytochrome c levels, retinal cell apoptosis, or retinal layer thickness at 1.5 μg/μL.
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Animal Model:genetically modified fat rats (diabetic retinal complication risk)[3]
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Dosage:7 mg/kg
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Administration:s.c.; three times weekly
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Result:Prevented the onset of diabetic retinal complications by reducing vascular leakage into the eye.
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Animal Model:BALB/c mice (either sex, 12.5-day-old pups, induced via two self-sealing uveal punctures with a 30G needle immediately posterior to the limbus, repeated every 4 days from experimental day 0 through day 12)[4]
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Dosage:7.6 g/L
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Administration:intravitreal; 3 injections (days 4, 8, 12); 1 μL per injection
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Result:Reduced iris macrovasculature density from a ~20% increase in rubeosis iridis eyes to non-punctured control levels by experimental day 8, with this effect sustained through day 15.
Reduced rubeosis iridis-associated microvascular changes (30% increases in total vasculature, sprouts, and vascular branching) back to control levels.
Normalized rubeosis iridis-induced 3.5-fold overexpression of FPR1 transcript levels to control levels, with no effect on FPR2 or FPR3.
Reduced rubeosis iridis-induced increased phosphorylation of CREB (p=0.002 versus rubeosis iridis) and NFκB (p=0.036 versus rubeosis iridis) back to control levels.
Normalized rubeosis iridis-induced overexpression of extracellular matrix degradation markers (PAI-1, uPA, uPAR) and inflammation markers (IL-1β, IL-6, TGFα, CCL2, CXCR4) at the transcript level to control levels.
Reduced rubeosis iridis-induced elevated IL-6 protein levels back to control levels, and reduced MMP2 protein levels significantly compared to rubeosis iridis eyes (p=0.036).
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Animal Model:BALB/c mice (either sex, 12.5-day-old pups, induced via two self-sealing uveal punctures with a 30G needle immediately posterior to the limbus, repeated every 4 days from experimental day 0 through day 12)[4]
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Dosage:15.2 mg/kg
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Administration:subcutaneous; daily; 5 days (day 4 through day 8)
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Result:Reduced rubeosis iridis-induced iris vascular density (over 25% increase at day 4) to non-punctured control levels by experimental day 8, with this effect sustained through day 15.
Normalized rubeosis iridis-induced overexpression of extracellular matrix degradation markers (PAI-1, uPA, uPAR) and inflammation markers (IL-1β, IL-6, CCL2, CXCR4) at the transcript level to control levels.
Reduced rubeosis iridis-induced elevated FPR1 transcript levels back to control levels.
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Animal Model:Sprague-Dawley (male, 150-200 g, streptozotocin-induced diabetic nephropathy)[5]
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Dosage:1 mg/kg; 8 mg/kg
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Administration:s.c.; daily; 5 days
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Result:Showed no significant effects on any measured parameters at 1 mg/kg.
Reduced renal uPA levels by 1.6-fold and renal uPA activity by 1.4-fold at 8 mg/kg.
Reduced plasma uPA levels by 1.2-fold and plasma uPA activity by 1.3-fold at 8 mg/kg.
Reduced glomerular FPR2 transcript levels by 1.3-fold at 8 mg/kg.
Reduced renal αvβ3 integrin levels by 1.6-fold at 8 mg/kg.
Reduced renal β3 integrin phosphorylation by 2.0-fold at 8 mg/kg.
Reduced renal Rac-1 activity by 1.2-fold at 8 mg/kg.
Reduced renal Plg levels by 1.7-fold at 8 mg/kg.
Increased renal plasmin levels by 1.5-fold and renal plasmin activity by 1.7-fold at 8 mg/kg.
Increased renal MMP-2 levels by 2.0-fold, renal MMP-9 levels by 1.7-fold, and renal MMP-2/MMP-9 activity by 1.9-fold at 8 mg/kg.
Increased plasma plasmin activity by 1.3-fold at 8 mg/kg.
Reduced renal fibronectin levels by 1.6-fold, renal collagen I levels by 3.1-fold, and renal collagen IV levels by 1.8-fold at 8 mg/kg.
Reduced glomerular fibrotic areas as measured by Masson's Trichrome staining at 8 mg/kg.
Reduced urine output by 1.7-fold, urine albumin by 1.8-fold, urine creatinine by 1.3-fold, albumin-to-creatinine ratio by 2.3-fold, plasma creatinine by 1.4-fold, creatinine clearance by 1.3-fold, and blood urea nitrogen by 1.7-fold at 8 mg/kg.
Increased renal ZO-1 levels by 1.7-fold and renal occludin levels by 1.8-fold at 8 mg/kg.
Reduced renal VEGF levels by 1.8-fold and Evans blue dye leakage by 1.4-fold at 8 mg/kg.
Increased renal medullary AQP2 levels by 2.8-fold and enhanced apical AQP2 localization in medullary collecting ducts at 8 mg/kg.
Reduced renal iNOS levels by 3.0-fold, renal ICAM-1 levels by 2.5-fold, renal NF-κB p65 phosphorylation by 3.8-fold, renal CREB phosphorylation by 2.4-fold, and renal HIF-1α levels by 3.9-fold at 8 mg/kg.
Reduced glomerular area by 1.1-fold and mesangial area by 1.2-fold at 8 mg/kg.
Attenuated glomerular basement membrane thickening and restored podocyte foot process architecture at 8 mg/kg.
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Animal Model:Sprague-Dawley (male, 150-200 g, streptozotocin-induced diabetic retinopathy)[6]
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Dosage:4 mg/kg (ERG); 8 mg/kg (ERG, BRB, markers); 10 mg/kg (safety); 20 mg/kg (Pharmacokinetic)
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Administration:s.c.; daily for 3 days; daily for 5 days; daily for 7 days; single dose
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Result:Restored scotopic ERG a-wave and b-wave amplitudes to levels not significantly different from non-diabetic controls.
Recovered b-wave Vmax to 736 μV (vs. 534 μV in untreated diabetic rats).
Recovered retinal sensitivity (k) to -1.38 log cd-s/m2 (vs. -0.3 log cd-s/m2 in untreated diabetic rats).
Maintained ERG recovery for approximately 2 weeks after treatment withdrawal.
Reduced diabetes-induced BRB leakage from ~2.3-fold above control levels to near-control levels.
Reduced retinal mRNA levels of inflammatory markers IL-1β by ~1.5-fold, IL-6 by ~1.3-fold, iNOS by ~1.4-fold, GFAP by ~1.4-fold relative to untreated/vehicle-treated diabetic rats.
Reduced retinal mRNA levels of proangiogenic markers VEGF by ~1.5-fold, IGF-1 by ~1.4-fold, FGF-2 by ~1.7-fold, PDGF-B by ~1.4-fold relative to untreated/vehicle-treated diabetic rats.
Restored ICAM-1 and Ang-2 levels to control levels.
Failed to restore ERG function at doses of 8 mg/kg daily for 3 days and 4 mg/kg daily for 5 days.
Achieved plasma Cmax of 5.9 μg/mL at 2 hours post single 20 mg/kg dose, terminal half-life of 3.0 hours, AUCinf of 34.4 μg-h/mL, with detectable plasma levels at 24 hours post-dose.
Reached concentration of 1.10 μg/g in the eye and 0.16 μg/g in the retina at 2 hours post single 20 mg/kg dose; reached concentration of 0.22 μg/g in the eye and 0.04 μg/g in the retina at 24 hours post-dose.
Showed no significant effects on body weight, hematologic/biochemical parameters, gross organ morphology, or liver/kidney histopathology at 10 mg/kg daily for 7 days.
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Animal Model:Sprague-Dawley (male, 150-200 g, healthy)[6]
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Dosage:20 mg/kg
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Administration:s.c.; single dose
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Result:Was quantifiable in plasma as early as 0.25 hours post-dose.
Reached peak plasma concentration (Cmax) of 5.9 μg/mL at 2 hours post-dose.
Remained detectable in plasma at 24 hours post-dose.
Reached concentration of 1.10 μg/g in the eye and 0.16 μg/g in the retina at 2 hours post-dose.
Reached concentration of 0.22 μg/g in the eye and 0.04 μg/g in the retina at 24 hours post-dose.
Had a terminal plasma half-life of 3.0 hours and AUCinf of 34.4 μg-h/mL.
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Animal Model:Spontaneously Diabetic Torii (SDT) rats (male, inbred from Sprague-Dawley rats, spontaneously developed hyperglycemia after 20 weeks of age leading to retinal impairment)[7]
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Dosage:7 mg/kg
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Administration:s.c.; 3 times a week; 19 weeks
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Result:Prevented ERG dysfunction, with a-wave and b-wave amplitudes across specified light intensities remaining not significantly different from non-diabetic Sprague-Dawley controls, while untreated/vehicle-treated rats showed significant amplitude reduction (P < 0.001).
Preserved b-wave Vmax (758.20 μV) and retinal sensitivity k (-1.31 log cd-s/m2), matching control values, whereas untreated/vehicle-treated rats had reduced Vmax and k (P < 0.001).
Prevented retinal vascular leakage, eliminating abnormal fluorescein leakage and vasodilation seen in untreated/vehicle-treated rats.
Prevented the 2.2-fold increase in Evans blue dye leakage (P < 0.001) seen in untreated/vehicle-treated rats, maintaining levels matching controls.
Restored transcript and protein levels of BRB markers (claudin-1, claudin-5, ZO-1) that were reduced by ~2-fold (P < 0.001) in untreated/vehicle-treated rats to levels not significantly different from controls.
Prevented retinal damage, reducing upregulated GFAP transcript (by 1.4-fold, P < 0.05) and protein (by ~2-fold, P < 0.001) levels, and upregulated caspase-3 transcript (by 1.3-fold, P < 0.05) and active caspase-3 protein (by ~1.4-fold, P < 0.01) levels seen in untreated/vehicle-treated rats, restoring values to near control levels.
Prevented upregulation of proangiogenic factors, reducing upregulated VEGF transcript (by ~1.2-fold, P < 0.05) and protein (by ~1.8-fold, P < 0.001) levels, and FGF-2 transcript (by ~2-fold, P < 0.01) and protein (by ~2.6-fold, P < 0.001) levels seen in untreated/vehicle-treated rats, restoring values to near control levels.
Modulated uPAR/FPR system and inflammatory pathways, reducing upregulated uPAR (by 1.7-fold, P < 0.01), FPR1 (by 1.8-fold, P < 0.01), and FPR2 (by 1.9-fold, P < 0.01) transcript and protein levels (no effect on FPR3).
Reduced phosphorylation of STAT3 (Tyr705) by 3.4-fold (P < 0.001) and NF-κB p65 (Ser276) by 1.6-fold (P < 0.001).
Reduced upregulated TNF-α transcript (by 1.4-fold, P < 0.01) and protein (by 1.6-fold, P < 0.01) levels, IL-1β transcript (by 1.7-fold, P < 0.01) and protein (by 2.1-fold, P < 0.001) levels, and IL-6 transcript (by 1.3-fold, P < 0.05) and protein (by 1.6-fold, P < 0.01) levels seen in untreated/vehicle-treated rats.
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Animal Model:Sprague-Dawley (SD) rats (male, type 1 diabetes induced by single intraperitoneal injection of 65 mg/kg streptozotocin)[7]
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Dosage:8 mg/kg
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Administration:s.c.; daily; 5 days
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Result:Reduced phosphorylation of STAT3 (Tyr705) by 3.0-fold (P < 0.01) and NF-κB p65 (Ser276) by 1.7-fold (P < 0.01) in streptozotocin-induced diabetic rats, which had shown 10.3-fold and 3.3-fold increases in phosphorylation (P < 0.001) compared to non-diabetic controls.
Showed no effect on upregulated uPAR, FPR1, FPR2, or FPR3 transcript and protein levels seen in streptozotocin-induced diabetic rats.
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Animal Model:C57BL/6J (male, 6-8 weeks old, 23-25 g)[8]
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Dosage:75 μg/kg; 150 μg/kg
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Administration:subcutaneous; single dose
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Result:Reduced hemoglobin content (a marker of vascularization) by 64% at the 75 μg/kg dose relative to VEGF-only controls.
Reduced hemoglobin content (a marker of vascularization) by 72% at the 150 μg/kg dose relative to VEGF-only controls.
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Animal Model:New Zealand White (female, 2.5-3.0 kg)[8]
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Dosage:5 μg per pellet
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Administration:subcorneal; single sustained-release dose
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Result:Reduced the median angiogenic score from 3.3 (VEGF-alone group) to 0.84, representing a 75% inhibition of VEGF-induced neovascularization.
Did not elicit an inflammatory or angiogenic response when administered alone.
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Animal Model:CD-1 mice; Wistar rats[9]
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Dosage:12 mg/kg; 24 mg/kg
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Administration:i.p.; single administration
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Result:Reduced inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX2), and nitric oxide (NO) overproduction in both inflammation models.
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Animal Model:Torii rats (genetically modified, diabetic)[9]
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Dosage:7 mg/kg
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Administration:s.c.; three times a week
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Result:Prevented onset of diabetes retinal complications by reducing vascular leakage into the eye.
Downregulated transcripts and proteins of blood-retinal barrier markers including claudin-1, claudin-5, and zonula occludens-1, restoring barrier integrity.
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Animal Model:Sprague-Dawley rats (streptozotocin-induced diabetic)[9]
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Dosage:8 mg/kg
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Administration:s.c.; daily; 5 days
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Result:Restored vascular permeability integrity.
Increased aquaporin-2 expression in the renal medulla.
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Animal Model:Unspecified rodent strain[9]
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Dosage:16 mg/kg
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Administration:s.c.; daily; postnatal day 10 to postnatal day 30
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Result:Significantly reduced the Bax:Bcl2 ratio and active caspase-3 levels.
Limited retinal cell apoptosis without affecting autophagy.
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Animal Model:CD-1 (male, 32-35 g, carrageenan-induced paw oedema model)[10]
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Dosage:6 mg/kg; 12 mg/kg; 24 mg/kg
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Administration:i.p.; single dose
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Result:Did not significantly affect paw oedema at 4 hours (265 μL) and 12 hours (261 μL) at 6 mg/kg dose.
Significantly reduced paw oedema to 180 μL at 4 hours and 165 μL at 12 hours at 12 mg/kg dose.
Significantly reduced paw oedema to 137 μL at 4 hours and 140 μL at 12 hours at 24 mg/kg dose.
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Animal Model:CD-1 (male, 32-35 g, carrageenan-induced paw oedema model)[10]
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Dosage:12 mg/kg; 24 mg/kg
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Administration:i.p.; 5 total doses (1 hour pre-carrageenan, then at 12, 24, 36, 48 hours post-carrageenan)
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Result:Reduced paw oedema to 80 μL at 12 hours post-carrageenan at 12 mg/kg dose.
Reduced paw oedema to 49 μL at 12 hours post-carrageenan at 24 mg/kg dose, with an effect comparable to dexamethasone.
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Animal Model:Wistar (male, 250-300 g, carrageenan-induced paw oedema model)[10]
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Dosage:6 mg/kg; 12 mg/kg; 24 mg/kg
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Administration:i.p.; single dose
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Result:Did not significantly affect paw oedema at 4 hours (2.25 mL) at 6 mg/kg dose.
Significantly reduced paw oedema to 1.35 mL at 4 hours at 12 mg/kg dose.
Significantly reduced paw oedema to 1.23 mL at 4 hours at 24 mg/kg dose.
Significantly reduced iNOS and COX-2 protein expression and NOx levels in paw exudates at 12 and 24 mg/kg doses.
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Animal Model:CD-1 (male, 32-35 g, zymosan-induced peritonitis model)[10]
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Dosage:6 mg/kg; 12 mg/kg; 24 mg/kg
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Administration:i.p.; single dose
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Result:Did not significantly reduce peritoneal cell influx (3433 × 104 cells) but significantly reduced NOx levels in peritoneal exudates at 6 mg/kg dose.
Significantly reduced peritoneal cell influx to 2233 × 104 cells and NOx levels in peritoneal exudates at 12 mg/kg dose.
Significantly reduced peritoneal cell influx to 2360 × 104 cells and NOx levels in peritoneal exudates at 24 mg/kg dose.
Chemical Information
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CAS. Nr. 1006388-38-0
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Appearance Solid
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Molecular Weight 617.74
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Formel C28H47N11O5
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Color White to off-white
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Synonyms
UPARANT
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Sequence
Ac-Arg-{Aib}-Arg-{aMePhe}-NH2
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Sequence Shortening
Ac-R-{Aib}-R-{aMePhe}-NH2
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Sealed storage, away from moisture
Powder -80°C 2 years -20°C 1 year * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Lösungsmittel & Löslichkeit
DMSO : 100 mg/mL (161.88 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
H2O : ≥ 100 mg/mL (161.88 mM)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
Reinheit & Dokumentation
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Data Sheet (327 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Handling Instructions (2659 KB)
Verweise
[1]. Motta C, et al. Molecular Mechanisms Mediating Antiangiogenic Action of the Urokinase Receptor-Derived Peptide UPARANT in Human Retinal Endothelial Cells. Investigative ophthalmology & visual science. 2016 Oct 01;57(13):5723-5735. [Content Brief]
[2]. Dal Monte M, et al. Antiangiogenic Effectiveness of the Urokinase Receptor-Derived Peptide UPARANT in a Model of Oxygen-Induced Retinopathy. Investigative ophthalmology & visual science. 2015 Apr;56(4):2392-407. [Content Brief]
[3]. Yuan C, et al. Development of inhibitors for uPAR: blocking the interaction of uPAR with its partners. Drug discovery today. 2021 Apr;26(4):1076-1085. [Content Brief]
[4]. Locri F, et al. UPARANT is an effective antiangiogenic agent in a mouse model of rubeosis iridis. Journal of molecular medicine (Berlin, Germany). 2019 Sep;97(9):1273-1283. [Content Brief]
[5]. Dal Monte M, et al. Inhibiting the urokinase-type plasminogen activator receptor system recovers STZ-induced diabetic nephropathy. Journal of cellular and molecular medicine. 2019 Feb;23(2):1034-1049. [Content Brief]
[6]. Cammalleri M, et al. The Urokinase Receptor-Derived Peptide UPARANT Recovers Dysfunctional Electroretinogram and Blood-Retinal Barrier Leakage in a Rat Model of Diabetes. Investigative ophthalmology & visual science. 2017 Jun 01;58(7):3138-3148. [Content Brief]
[7]. Cammalleri M, et al. Diabetic Retinopathy in the Spontaneously Diabetic Torii Rat: Pathogenetic Mechanisms and Preventive Efficacy of Inhibiting the Urokinase-Type Plasminogen Activator Receptor System. Journal of diabetes research. 2017;2017:2904150. [Content Brief]
[8]. Carriero MV, et al. UPARANT: a urokinase receptor-derived peptide inhibitor of VEGF-driven angiogenesis with enhanced stability and in vitro and in vivo potency. Molecular cancer therapeutics. 2014 May;13(5):1092-104. [Content Brief]
[9]. D'Alonzo D, et al. COVID-19 and pneumonia: a role for the uPA/uPAR system. Drug discovery today. 2020 Aug;25(8):1528-1534. [Content Brief]
[10]. Boccella S, et al. Preclinical evaluation of the urokinase receptor-derived peptide UPARANT as an anti-inflammatory drug. Inflammation research : official journal of the European Histamine Research Society ... [et al.]. 2017 Aug;66(8):701-709. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO / H2O | 1 mM | 1.6188 mL | 8.0940 mL | 16.1880 mL | 40.4701 mL |
| 5 mM | 0.3238 mL | 1.6188 mL | 3.2376 mL | 8.0940 mL | |
| 10 mM | 0.1619 mL | 0.8094 mL | 1.6188 mL | 4.0470 mL | |
| 15 mM | 0.1079 mL | 0.5396 mL | 1.0792 mL | 2.6980 mL | |
| 20 mM | 0.0809 mL | 0.4047 mL | 0.8094 mL | 2.0235 mL | |
| 25 mM | 0.0648 mL | 0.3238 mL | 0.6475 mL | 1.6188 mL | |
| 30 mM | 0.0540 mL | 0.2698 mL | 0.5396 mL | 1.3490 mL | |
| 40 mM | 0.0405 mL | 0.2024 mL | 0.4047 mL | 1.0118 mL | |
| 50 mM | 0.0324 mL | 0.1619 mL | 0.3238 mL | 0.8094 mL | |
| 60 mM | 0.0270 mL | 0.1349 mL | 0.2698 mL | 0.6745 mL | |
| 80 mM | 0.0202 mL | 0.1012 mL | 0.2024 mL | 0.5059 mL | |
| 100 mM | 0.0162 mL | 0.0809 mL | 0.1619 mL | 0.4047 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Cenupatide Related Classifications
HY-P1615 Related Classifications
Powered by Bioz
- Cenupatide
- 1006388-38-0
- UPARANT
- Transmembrane Glycoprotein
- Formyl Peptide Receptor (FPR)
- VEGFR
- Akt
- STAT
- JNK
- p38 MAPK
- ERK
- NF-κB
- Apoptosis
- Integrin
- diabetic retinopathy
- uPAR
- retinal neovascularization
- primary human retinal endothelial cells
- HUVEC
- blood-retinal barrier
- rubeosis iridis
- renal fibrosis
- VEGF
- FPR
- Inhibitor
- inhibitor
- inhibit