Klotho-derived peptide 1 hydrochloride
Based on 1 Customer Validation
Klotho-derived peptide 1 hydrochloride (KP1 (human) hydrochloride) is a polypeptide with multiple activities including senescence inhibition and renal protection. Klotho-derived peptide 1 hydrochloride binds to TβR2 and ATAD3A, with a Kd value of 1.41 μM for binding to human TβR2 and a Kd value of 0.319 μM for binding to ATAD3A. By binding to TβR2, Klotho-derived peptide 1 hydrochloride blocks the TGF-β/Smad3 and downstream TGF-β signaling pathways, inhibits the expression of miR-223-3p, induces the expression of lncRNA-TUG1, restores endogenous Klotho at the post-transcriptional level, inhibits cellular senescence markers, fibroblast activation and renal tubular epithelial cell apoptosis, blocks cytochrome c release and caspase activation, maintains the integrity of mitochondrial ultrastructure, and restores mitochondrial protein levels. Klotho-derived peptide 1 hydrochloride enters renal tubular epithelial cells via endocytosis, protects against nephrotoxic and hypoxic injuries, and recapitulates the renal protective and anti-fibrotic effects of full-length Klotho. Klotho-derived peptide 1 hydrochloride can be used in research related to kidney diseases such as chronic kidney disease and SARS-CoV-2-associated acute kidney injury.
For research use only. We do not sell to patients.
- Purity: 99.67%
- Formula: C149H203N39O43.xHCl
- Molecular Weight:3228.44 (free base)
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Storage:
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)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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TGF-βR2 1.41 μM (Kd) |
Klotho-derived peptide 1 (KP1) hydrochloride inhibits TGF-β1-induced cellular senescence in HK-2 cells via post-transcriptional regulation, and restores the expression of mKlotho and sKlotho proteins; it suppresses miR-223-3p, restores the expression of mKlotho, sKlotho and lncRNA-TUG1, and inhibits miR-223-3p-induced cellular senescence and the expression of fibrosis markers in HK-2 cells[1].
Klotho-derived peptide 1 hydrochloride inhibits the TGF-β/Smad3/miR-223-3p axis, restores the protein expression of mKlotho and sKlotho, and antagonizes TGF-β1-induced cellular senescence and fibrosis in HK-2 cells[1].
Klotho-derived peptide 1 hydrochloride binds tightly to recombinant human transforming growth factor-β receptor 2, with an equilibrium dissociation constant (KD) of 1.41 μM[3].
Klotho-derived peptide 1 hydrochloride specifically binds to recombinant human transforming growth factor β receptor 2; it also binds to endogenous TGF-β receptor 2 in lysates of normal rat renal interstitial fibroblasts (NRK-49F)[3].
Klotho-derived peptide 1 hydrochloride inhibits TGF-β1-induced myofibroblast activation, extracellular matrix protein expression, and both canonical and non-canonical TGF-β signaling pathways; it suppresses TGF-β1-induced extracellular matrix protein expression and Smad2/3 phosphorylation; it blocks the binding of TGF-β1 to TGF-β receptor 2, the formation of TGF-β receptor 1/TGF-β receptor 2 heterodimers, and the interaction between soluble Klotho and TGF-β receptor 2[3].
Klotho-derived peptide 1 hydrochloride binds to ATAD3A with high affinity (Kd = 3.19×10-7 M) in cell-free MST binding assays using lysates transfected with GFP-ATAD3A; it stabilizes ATAD3A in a dose-dependent manner in cell-free DARTS assays using lysates with overexpressed ATAD3A[4].
Klotho-derived peptide 1 (3 μM; 1 h) hydrochloride restores the Cisplatin-reduced levels of ATAD3A and HIGD2A proteins in HKC-8 renal tubular epithelial cells, and inhibits the release of cytochrome c from mitochondria[4].
Klotho-derived peptide 1 (10 μg/mL; 48 h) hydrochloride protects human renal proximal tubular HK-2 cells from injury and apoptosis induced by SARS-CoV-2 N protein, eliminates the upregulation of injury and apoptosis markers, and reduces the proportion of apoptotic cells[2].
Klotho-derived peptide 1 (3 μM; 1 h) hydrochloride protects primary mouse proximal tubular epithelial cells against Cisplatin (HY-17394)- and H/R-induced injury, apoptosis, and mitochondrial dysfunction[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human kidney proximal tubular cells (HK-2)
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Concentration:10 μg/mL
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Incubation Time:48 h
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Result:Abolished the SARS-CoV-2 N protein-induced upregulation of kidney injury molecule-1 (KIM-1), cleaved poly-ADP-ribose polymerase (PARP), p53, and FAS-associated protein with death domain (FADD).
Negated the increase in TUNEL-positive apoptotic cells induced by N protein, with efficacy comparable to recombinant human Klotho.
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Cell Line:HKC-8 human renal tubular epithelial cells (Cisplatin-induced injury model and hypoxia/reoxygenation [H/R]-induced injury model)
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Concentration:3 μM (KP1); 7 μg/mL (Cisplatin)
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Incubation Time:1 h (KP1 pre-incubation); 24 h (cisplatin incubation)
1 h (KP1 pre-incubation); 24 h (hypoxia); 4-6 h (reoxygenation) -
Result:Completely restored cisplatin-depleted ATAD3A protein levels in HKC-8 cells.\nRestored cisplatin-depleted HIGD2A protein levels and reversed cytochrome c translocation from mitochondria to cytosol in HKC-8 cells.
Completely restored H/R-depleted ATAD3A protein levels in HKC-8 cells. Restored H/R-depleted HIGD2A protein levels and reversed cytochrome c translocation from mitochondria to cytosol in HKC-8 cells.
Klotho-derived peptide 1 (1 mg/kg/day; i.v.; daily; 7 days starting day 4 post-surgery) hydrochloride inhibits cellular senescence, restores Klotho protein expression, improves kidney function, and suppresses fibrosis in UIRI-induced chronic kidney disease by inhibiting miR-223-3p[1].
Klotho-derived peptide 1 (1 mg/kg/day; i.v.; daily starting day 1 post-surgery) hydrochloride mitigates shTUG1-induced kidney injury in UUO-induced chronic kidney disease by restoring lncRNA-TUG1 and Klotho protein expression, and inhibiting miR-223-3p[1].
Klotho-derived peptide 1 (1 mg/kg/day; i.v.; daily starting day 4 post-surgery) hydrochloride reverses miR-223-3p-induced Klotho reduction, cellular senescence, fibrosis, and kidney dysfunction in UIRI-induced chronic kidney disease[1].
Klotho-derived peptide 1 (1 mg/kg; i.v.; daily; 4 days) hydrochloride ameliorates acute kidney injury induced by SARS-CoV-2 N protein and ischemia-reperfusion injury in male C57BL/6 mice, as evidenced by reduced serum creatinine and blood urea nitrogen levels, restored Klotho expression, inhibited injury marker induction, and suppressed tubular apoptosis[2].
Klotho-derived peptide 1 (1 mg/kg; i.v.; daily; 7 consecutive days) hydrochloride preserves kidney function, reduces renal fibrosis by ~60%, inhibits TGF-β signaling, and restores endogenous Klotho expression in male BALB/c mice with unilateral ischemia-reperfusion injury[3].
Klotho-derived peptide 1 (1 mg/kg; i.v.; daily; 6 consecutive days) hydrochloride reduces renal fibrosis by ~50%, inhibits TGF-β signaling and renal inflammation, and restores endogenous Klotho expression in male BALB/c mice with unilateral ureter obstruction[3].
Klotho-derived peptide 1 (KP1) (5 mg/kg; daily; 2 days pre-cisplatin) hydrochloride protects against cisplatin-induced acute kidney injury in male C57BL/6 mice by reducing renal dysfunction, injury marker expression, tubular apoptosis, and restoring mitochondrial protein levels[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (male, 8-10 weeks old, unilateral ureteral obstruction model)[1]
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Dosage:1 mg/kg/day
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Administration:i.v.; daily; 6 days starting day 1 post-surgery
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Result:Abolished the induction of cellular senescence markers p21, p16, and γ-H2AX in kidney tissue.
Restored renal expression of membranous Klotho (mKlotho) and soluble Klotho (sKlotho) proteins, but did not affect Klotho mRNA levels.
Inhibited upregulation of fibrotic markers fibronectin, collagen I, and α-SMA in kidney tissue.
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Animal Model:C57BL/6 (male, 8-10 weeks old, unilateral ischemia-reperfusion injury model)[1]
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Dosage:1 mg/kg/day
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Administration:i.v.; daily; 7 days starting day 4 post-surgery
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Result:Eliminated tubular cellular senescence markers including p21, p16 and γ-H2AX as well as SA-β-Gal, recovered mKlotho and sKlotho protein abundance without altering Klotho transcription, lowered fibronectin, collagen I and α-SMA fibrotic markers, relieved renal dysfunction via declined serum creatinine and BUN, and inhibited UIRI-triggered renal miR-223-3p overexpression.
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Animal Model:C57BL/6 (male, 8-10 weeks old, unilateral ureteral obstruction model)[1]
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Dosage:1 mg/kg/day (Klotho-derived peptide 1); 2.5 mg/kg (shTUG1 plasmid)
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Administration:i.v.; daily starting day 1 post-surgery (Klotho-derived peptide 1); i.v.; single dose day 1 post-surgery (shTUG1 plasmid)
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Result:Recovered shTUG1-suppressed renal lncRNA-TUG1 expression, restrained shTUG1-evoked renal miR-223-3p elevation, restored shTUG1-depleted mKlotho and sKlotho protein without changing Klotho mRNA, erased shTUG1-induced p21, p16 and γ-H2AX senescence markers, and suppressed shTUG1-triggered overexpression of fibronectin, collagen I and α-SMA fibrotic proteins.
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Animal Model:C57BL/6 (male, 8-10 weeks old, unilateral ischemia-reperfusion injury model)[1]
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Dosage:1 mg/kg/day (Klotho-derived peptide 1); 2.5 mg/kg (miR-223-3p overexpression plasmid)
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Administration:i.v.; daily starting day 4 post-surgery (Klotho-derived peptide 1); i.v.; single dose day 4 post-surgery (miR-223-3p overexpression plasmid)
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Result:Reduced the elevated renal miR-223-3p levels induced by the overexpression plasmid.
Restored mKlotho and sKlotho protein expression that was suppressed by miR-223-3p overexpression, without affecting Klotho mRNA levels.
Abolished the exacerbated induction of cellular senescence markers p16 and γ-H2AX caused by miR-223-3p overexpression.
Inhibited the increased expression of fibrotic markers fibronectin, collagen I, and α-SMA triggered by miR-223-3p overexpression.
Improved kidney function as measured by decreased serum creatinine and blood urea nitrogen levels.
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Animal Model:BALB/c (male, 20-22 g, unilateral ischemia-reperfusion injury)[3]
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Dosage:1 mg/kg
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Administration:i.v.; daily; 7 consecutive days
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Result:Selectively enriched in damaged kidney tissue with negligible deposition in healthy kidney and other visceral organs, and alleviated renal dysfunction by lowering serum creatinine and BUN concentrations.
Markedly shrank renal fibrotic lesions and diminished fibronectin/α-SMA positive interstitial regions, while decreasing profibrotic protein fibronectin, α-SMA and collagen expression in kidney tissues.
Interrupted TGF-β1/TβR2 signaling cascade via downregulating phosphorylated Smad, MAPK and TβR2 proteins, and rescued renal endogenous Klotho protein abundance.
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Animal Model:BALB/c (male, 20-22 g, unilateral ureter obstruction)[3]
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Dosage:1 mg/kg
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Administration:i.v.; daily; 6 consecutive days
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Result:Accumulated selectively in obstructed renal tissue (~12 ng/mg) with far lower distribution in normal kidney and visceral organs, and localized mainly to renal tubular epithelial cells. It cut renal fibrotic region and vimentin-positive cell numbers by roughly half.
Downregulated fibronectin, α-SMA and collagen I renal protein abundance by about 65%, 80% and 80%, disrupted TGF-β cascade by lowering phosphorylated Smad2/3, ERK/JNK/p38 and TβR2 protein levels.
Eliminated renal F4/80 macrophage marker, suppressed immune cell infiltration, and recovered renal Klotho protein expression and positive staining area to prominent levels.
Chemical Information
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Appearance Solid
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Molecular Weight 3228.44 (free base)
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Formula C149H203N39O43.xHCl
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Color White to off-white
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Synonyms
KP1 (human) hydrochloride
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Sequence
Phe-Gln-Gly-Thr-Phe-Pro-Asp-Gly-Phe-Leu-Trp-Ala-Val-Gly-Ser-Ala-Ala-Tyr-Gln-Thr-Glu-Gly-Gly-Trp-Gln-Gln-His-Gly-Lys-Gly
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Sequence Shortening
FQGTFPDGFLWAVGSAAYQTEGGWQQHGKG
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
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)
Solvent & Solubility
H2O : 50 mg/mL (Need ultrasonic)
0.1 M Acetic acid : 50 mg/mL (adjust pH to 2 with CH3COOH)
Purity & Documentation
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Data Sheet (298 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[1]. Zhang X, et al. Klotho-derived peptide 1 inhibits cellular senescence in the fibrotic kidney by restoring Klotho expression via posttranscriptional regulation. Theranostics. 2024;14(1):420-435. [Content Brief]
[2]. Xu J, et al. Klotho-derived peptide KP1 ameliorates SARS-CoV-2-associated acute kidney injury. Frontiers in pharmacology. 2023;14:1333389. [Content Brief]
[3]. Yuan Q, et al. A Klotho-derived peptide protects against kidney fibrosis by targeting TGF-β signaling. Nature communications. 2022 Jan 21;13(1):438. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Klotho-derived peptide 1 hydrochloride Related Classifications
HY-P10414A Related Classifications
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