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Chemical Structure| 82009-34-5 Chemical Structure| 82009-34-5

Structure of Cilastatin
CAS No.: 82009-34-5

Chemical Structure| 82009-34-5

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Cilastatin is a renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor.

Synonyms: MK0791

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Product Citations

Product Citations

Martinez-Erro, Samuel ; Navas, Francisco ; Romani-Cubells, Eva ; Fernandez-Garcia, Paloma ; Morales, Victoria ; Sanz, Raul , et al.

Abstract: Mesoporous silica nanomaterials have emerged as promising vehicles in controlled drug delivery systems due to their ability to selectively transport, protect, and release pharmaceuticals in a controlled and sustained manner. One drawback of these drug delivery systems is their preparation procedure that usually requires several steps including the removal of the structure-directing agent (surfactant) and the later loading of the drug into the porous structure. Herein, we describe the preparation of mesoporous silica nanoparticles, as drug delivery systems from structure-directing agents based on the kidney-protector drug cilastatin in a simple, fast, and one-step process. The concept of drug-structure-directing agent (DSDA) allows the use of lipidic derivatives of cilastatin to direct the successful formation of mesoporous silica nanoparticles (MSNs). The inherent pharmacol. activity of the surfactant DSDA cilastatin-based template permits that the MSNs can be directly employed as drug delivery nanocarriers, without the need of extra steps. MSNs thus synthesized have shown good sphericity and remarkable textural properties. The size of the nanoparticles can be adjusted by simply selecting the stirring speed, time, and aging temperature during the synthesis procedure. Moreover, the release experiments performed on these materials afforded a slow and sustained drug release over several days, which illustrates the MSNs potential utility as drug delivery system for the cilastatin cargo kidney protector. While most nanotechnol. strategies focused on combating the different illnesses this methodol. emphasizes on reducing the kidney toxicity associated to cancer chemotherapy.

Keywords: cilastatin ; drug delivery systems ; drug-structure-directing agent (DSDA) ; mesoporous silica nanoparticles (MSNs) ; sustained and controlled release

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Product Details of Cilastatin

CAS No. :82009-34-5
Formula : C16H26N2O5S
M.W : 358.45
SMILES Code : O=C(O)/C(NC([C@@H]1C(C)(C)C1)=O)=C/CCCCSC[C@H](N)C(O)=O
Synonyms :
MK0791
MDL No. :MFCD00867379

Safety of Cilastatin

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Renal primary proximal tubule cells (RPTCs) 100 μM 24 h To evaluate the protective effect of Cilastatin against diclofenac-induced cytotoxicity. Results showed that Cilastatin reduced the cytotoxicity of diclofenac acyl glucuronide (DLF-AG) by inhibiting OAT1/3-mediated intracellular accumulation. Br J Pharmacol. 2020 May;177(9):1933-1948.
HEK293 cells 100 μM 24 h To evaluate the protective effect of Cilastatin against diclofenac-induced cytotoxicity. Results showed that Cilastatin reduced the cytotoxicity of diclofenac acyl glucuronide (DLF-AG) by inhibiting OAT1/3-mediated intracellular accumulation. Br J Pharmacol. 2020 May;177(9):1933-1948.
Porcine renal proximal tubular epithelial cells (RPTECs) 200 µg/mL 24 h To evaluate the protective effect of Cilastatin against gentamicin-induced apoptosis. Results showed that Cilastatin reduced cell detachment, preserved cell morphology, and decreased caspase-3 activation and DNA fragmentation. Antioxidants (Basel). 2020 Sep 3;9(9):821
rabbit primary proximal tubule cells (rPTCs) 100 µM 10 min To investigate the inhibitory effect of Cilastatin on Imipenem uptake in rPTCs, results showed that Cilastatin inhibited raOATs-mediated transport of Imipenem. Acta Pharm Sin B. 2019 Sep;9(5):986-996
hOAT3-HEK293 cells 100 µM 10 min To investigate the inhibitory effect of Cilastatin on Imipenem uptake in hOAT3-HEK293 cells, results showed that Cilastatin inhibited hOAT3-mediated transport of Imipenem. Acta Pharm Sin B. 2019 Sep;9(5):986-996
hOAT1-HEK293 cells 100 µM 10 min To investigate the inhibitory effect of Cilastatin on Imipenem uptake in hOAT1-HEK293 cells, results showed that Cilastatin inhibited hOAT1-mediated transport of Imipenem. Acta Pharm Sin B. 2019 Sep;9(5):986-996

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Kunming mice Diclofenac-induced acute kidney injury model Intraperitoneal injection 25, 50, 100 mg/kg Single dose To evaluate the protective effect of Cilastatin against diclofenac-induced acute kidney injury. Results showed that Cilastatin alleviated diclofenac-induced acute kidney injury by restoring the redox balance, suppressing inflammation, and reducing apoptosis. Br J Pharmacol. 2020 May;177(9):1933-1948.
Wistar rats Gentamicin-induced acute kidney injury model Intraperitoneal injection 150 mg/kg Once daily for 8 days To evaluate the protective effect of Cilastatin against gentamicin-induced renal injury. Results showed that Cilastatin reduced serum creatinine, BUN, KIM-1 levels, improved renal morphology, and decreased oxidative stress and inflammatory responses. Antioxidants (Basel). 2020 Sep 3;9(9):821
Female Wistar rats Cisplatin-induced nephrotoxicity model Intraperitoneal injection 150 mg/kg Once daily for 5 days Cilastatin significantly alleviated cisplatin-induced nephrotoxicity, including weight loss, renal dysfunction (elevated serum creatinine and BUN), and renal tissue damage. Additionally, Cilastatin reduced cisplatin-induced apoptosis and lipid peroxidation and restored alterations in renal lipid distribution. J Lipid Res. 2018 Sep;59(9):1561-1574
New Zealand white rabbits Imipenem-induced acute kidney injury model Intravenous injection 200 mg/kg Single dose, observed for 48 hours To investigate the protective effect of Cilastatin on imipenem-induced kidney injury, results showed that Cilastatin alleviated imipenem-induced kidney injury. Acta Pharm Sin B. 2019 Sep;9(5):986-996

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.79mL

0.56mL

0.28mL

13.95mL

2.79mL

1.39mL

27.90mL

5.58mL

2.79mL

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