Cilastatin | CAS#82009-34-5 | Dehydropeptidase-I & leukotriene D4 Dipeptidase inhibitor

MedKoo Cat#: 524736 | Name: Cilastatin

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Cilastatin is a renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Dehydropeptidase is an enzyme found in the kidney and is responsible for degrading the antibiotic imipenem. Cilastatin can therefore be combined intravenously with imipenem in order to protect it from dehydropeptidase and prolong its antibacterial effect. Cilastatin itself does not have antibiotic activity although it has been proved to be active against a zinc-dependent beta-lactamase that usually confer antibiotic resistance to certain bacteria.

Chemical Structure

Cilastatin

CAS#82009-34-5 (free acid)

Theoretical Analysis

MedKoo Cat#: 524736

Name: Cilastatin

CAS#: 82009-34-5 (free acid)

Chemical Formula: C16H26N2O5S

Exact Mass: 358.1562

Molecular Weight: 358.45

Elemental Analysis: C, 53.61; H, 7.31; N, 7.82; O, 22.32; S, 8.95

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,350.00	2 Weeks
500mg	USD 2,850.00	2 Weeks

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Related CAS #

81129-83-1 (sodium) 82009-34-5 (free acid)

Synonym

Cilastatin; MK 0791; MK-0791; MK0791; MK 791; M K-791; MK0791; MK791;

IUPAC/Chemical Name

2-Heptenoic acid, 7-((2-amino-2-carboxyethyl)thio)-2-(((2,2-dimethylcyclopropyl)carbonyl)amino)-, (R-(R*,S*-(Z)))-

InChi Key

DHSUYTOATWAVLW-WFVMDLQDSA-N

InChi Code

InChI=1S/C16H26N2O5S/c1-16(2)8-10(16)13(19)18-12(15(22)23)6-4-3-5-7-24-9-11(17)14(20)21/h6,10-11H,3-5,7-9,17H2,1-2H3,(H,18,19)(H,20,21)(H,22,23)/b12-6-/t10-,11+/m1/s1

SMILES Code

[C@H]1(C(C1)(C)C)C(=O)N/C(=C\CCCCSC[C@@H](C(=O)O)N)C(=O)O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Cilastatin (MK0791) is a reversible, competitive renal dehydropeptidase I inhibitor with an IC50 of 0.1 μM.

In vitro activity:

Cilastatin preconditioning and IR exposure increased HIF-1α level compared with control group (Figure 4A). Cilastatin preconditioning further enhanced the HIF-1α expression in IR-exposed cells than in non-exposed cells. Reference: Int J Mol Sci. 2020 May; 21(10): 3583. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279043/

In vivo activity:

Administration of the pharmacologic megalin inhibitor cilastatin to wild-type mice recapitulated the renoprotective effects of megalin deletion. This cilastatin-mediated renoprotective effect was dependent on megalin. Cilastatin administration caused selective proteinuria and inhibition of tubular myoglobin uptake similar to that caused by megalin deletion. Reference: J Am Soc Nephrol. 2021 Aug 2:ASN.2020030263. https://pubmed.ncbi.nlm.nih.gov/34341182/

	Solvent	mg/mL	mM
Solubility
	DMSO	10.0	27.90
	DMF	10.0	27.90

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 358.45 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Hong YA, Jung SY, Yang KJ, Im DS, Jeong KH, Park CW, Hwang HS. Cilastatin Preconditioning Attenuates Renal Ischemia-Reperfusion Injury via Hypoxia Inducible Factor-1α Activation. Int J Mol Sci. 2020 May 19;21(10):3583. doi: 10.3390/ijms21103583. PMID: 32438631; PMCID: PMC7279043. 2. Luo K, Lim SW, Jin J, Jin L, Gil HW, Im DS, Hwang HS, Yang CW. Cilastatin protects against tacrolimus-induced nephrotoxicity via anti-oxidative and anti-apoptotic properties. BMC Nephrol. 2019 Jun 14;20(1):221. doi: 10.1186/s12882-019-1399-6. PMID: 31200653; PMCID: PMC6570925. 3. Matsushita K, Mori K, Saritas T, Eiwaz M, Funahashi Y, Nickerson M, Hebert J, Munhall A, McCormick J, Yanagita M, Hutchens M. Cilastatin Ameliorates Rhabdomyolysis-Induced Acute Kidney Injury in Mice. J Am Soc Nephrol. 2021 Aug 2:ASN.2020030263. doi: 10.1681/ASN.2020030263. Epub ahead of print. PMID: 34341182. 4. Jado JC, Humanes B, González-Nicolás MÁ, Camaño S, Lara JM, López B, Cercenado E, García-Bordas J, Tejedor A, Lázaro A. Nephroprotective Effect of Cilastatin against Gentamicin-Induced Renal Injury In Vitro and In Vivo without Altering Its Bactericidal Efficiency. Antioxidants (Basel). 2020 Sep 3;9(9):821. doi: 10.3390/antiox9090821. PMID: 32899204; PMCID: PMC7555100.

In vitro protocol:

In vivo protocol:

1. Matsushita K, Mori K, Saritas T, Eiwaz M, Funahashi Y, Nickerson M, Hebert J, Munhall A, McCormick J, Yanagita M, Hutchens M. Cilastatin Ameliorates Rhabdomyolysis-Induced Acute Kidney Injury in Mice. J Am Soc Nephrol. 2021 Aug 2:ASN.2020030263. doi: 10.1681/ASN.2020030263. Epub ahead of print. PMID: 34341182. 2. Jado JC, Humanes B, González-Nicolás MÁ, Camaño S, Lara JM, López B, Cercenado E, García-Bordas J, Tejedor A, Lázaro A. Nephroprotective Effect of Cilastatin against Gentamicin-Induced Renal Injury In Vitro and In Vivo without Altering Its Bactericidal Efficiency. Antioxidants (Basel). 2020 Sep 3;9(9):821. doi: 10.3390/antiox9090821. PMID: 32899204; PMCID: PMC7555100.

1: Davani F, Alishahi M, Sabzi M, Khorram M, Arastehfar A, Zomorodian K. Dual drug delivery of vancomycin and imipenem/cilastatin by coaxial nanofibers for treatment of diabetic foot ulcer infections. Mater Sci Eng C Mater Biol Appl. 2021 Apr;123:111975. doi: 10.1016/j.msec.2021.111975. Epub 2021 Feb 15. PMID: 33812603. 2: Heo YA. Imipenem/Cilastatin/Relebactam: A Review in Gram-Negative Bacterial Infections. Drugs. 2021 Feb;81(3):377-388. doi: 10.1007/s40265-021-01471-8. Epub 2021 Feb 25. PMID: 33630278; PMCID: PMC7905759. 3: Yamada K, Jahangiri Y, Li J, Gabr A, Anoushiravani A, Kumagai K, Uchida B, Farsad K, Horikawa M. Embolic Characteristics of Imipenem-Cilastatin Particles in Vitro and in Vivo: Implications for Transarterial Embolization in Joint Arthropathies. J Vasc Interv Radiol. 2021 Feb 16:S1051-0443(21)00336-5. doi: 10.1016/j.jvir.2021.02.006. Epub ahead of print. PMID: 33607251. 4: Mansour H, Ouweini AEL, Chahine EB, Karaoui LR. Imipenem/cilastatin/relebactam: A new carbapenem β-lactamase inhibitor combination. Am J Health Syst Pharm. 2021 Mar 31;78(8):674-683. doi: 10.1093/ajhp/zxab012. PMID: 33580649. 5: He M, Souza E, Matvekas A, Crass RL, Pai MP. Alteration in Acute Kidney Injury Potential with the Combination of Vancomycin and Imipenem- Cilastatin/Relebactam or Piperacillin/Tazobactam in a Preclinical Model. Antimicrob Agents Chemother. 2021 Mar 18;65(4):e02141-20. doi: 10.1128/AAC.02141-20. PMID: 33526494. 6: Zaballos M, Power M, Canal-Alonso MI, González-Nicolás MÁ, Vasquez-Jimenez W, Lozano-Lominchar P, Cabrerizo-Torrente P, Palencia-García N, Gago-Quiroga S, Ginel-Feito MD, Jiménez C, Lázaro A, González-Bayón L. Effect of Cilastatin on Cisplatin-Induced Nephrotoxicity in Patients Undergoing Hyperthermic Intraperitoneal Chemotherapy. Int J Mol Sci. 2021 Jan 27;22(3):1239. doi: 10.3390/ijms22031239. PMID: 33513824; PMCID: PMC7865672. 7: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006–. Imipenem and Cilastatin. 2021 Jan 18. PMID: 30000046. 8: Arita M, Watanabe S, Aoki N, Kuwahara S, Suzuki R, Goto S, Abe Y, Takahashi M, Sato M, Hokari S, Ohtsubo A, Shoji S, Nozaki K, Ichikawa K, Kondo R, Hayashi M, Ohshima Y, Kabasawa H, Hosojima M, Koya T, Saito A, Kikuchi T. Combination therapy of cisplatin with cilastatin enables an increased dose of cisplatin, enhancing its antitumor effect by suppression of nephrotoxicity. Sci Rep. 2021 Jan 12;11(1):750. doi: 10.1038/s41598-020-80853-6. PMID: 33437029; PMCID: PMC7804437. 9: Kohno S, Bando H, Yoneyama F, Kikukawa H, Kawahara K, Shirakawa M, Aoyama N, Brown M, Paschke A, Takase A. The safety and efficacy of relebactam/imipenem/cilastatin in Japanese patients with complicated intra- abdominal infection or complicated urinary tract infection: A multicenter, open- label, noncomparative phase 3 study. J Infect Chemother. 2021 Feb;27(2):262-270. doi: 10.1016/j.jiac.2020.09.032. Epub 2020 Nov 13. PMID: 33191112. 10: Chen IH, Nicolau DP, Kuti JL. Imipenem/Cilastatin/Relebactam Alone and in Combination against Pseudomonas aeruginosa in the In Vitro Pharmacodynamic Model. Antimicrob Agents Chemother. 2020 Nov 17;64(12):e01764-20. doi: 10.1128/AAC.01764-20. PMID: 33139283; PMCID: PMC7674065. 11: González-Nicolás MÁ, González-Guerrero C, Pérez-Fernández VA, Lázaro A. Cilastatin: a potential treatment strategy against COVID-19 that may decrease viral replication and protect from the cytokine storm. Clin Kidney J. 2020 Sep 24;13(5):903-905. doi: 10.1093/ckj/sfaa193. PMID: 33117530; PMCID: PMC7543365. 12: Sakoulas G. Case Commentary: Imipenem/Cilastatin and Fosfomycin for Refractory Methicillin-Resistant Staphylococcus aureus Infection: a Novel Combination Therapy. Antimicrob Agents Chemother. 2020 Dec 16;65(1):e02039-20. doi: 10.1128/AAC.02039-20. PMID: 33020155; PMCID: PMC7927839. 13: Oho M, Funashima Y, Nagasawa Z, Miyamoto H, Sueoka E. Rapid detection method of carbapenemase-producing Enterobacteriaceae by MALDI-TOF MS with imipenem/cilastatin (KB) disc and zinc sulfate solution. J Infect Chemother. 2021 Feb;27(2):205-210. doi: 10.1016/j.jiac.2020.09.013. Epub 2020 Sep 29. PMID: 33008738. 14: Jado JC, Humanes B, González-Nicolás MÁ, Camaño S, Lara JM, López B, Cercenado E, García-Bordas J, Tejedor A, Lázaro A. Nephroprotective Effect of Cilastatin against Gentamicin-Induced Renal Injury In Vitro and In Vivo without Altering Its Bactericidal Efficiency. Antioxidants (Basel). 2020 Sep 3;9(9):821. doi: 10.3390/antiox9090821. PMID: 32899204; PMCID: PMC7555100. 15: Kuiper SG, Leegwater E, Wilms EB, van Nieuwkoop C. Evaluating imipenem + cilastatin + relebactam for the treatment of complicated urinary tract infections. Expert Opin Pharmacother. 2020 Oct;21(15):1805-1811. doi: 10.1080/14656566.2020.1790525. Epub 2020 Aug 21. PMID: 32820669. 16: Titov I, Wunderink RG, Roquilly A, Rodríguez Gonzalez D, David-Wang A, Boucher HW, Kaye KS, Losada MC, Du J, Tipping R, Rizk ML, Patel M, Brown ML, Young K, Kartsonis NA, Butterton JR, Paschke A, Chen LF. A Randomized, Double- blind, Multicenter Trial Comparing Efficacy and Safety of Imipenem/Cilastatin/Relebactam Versus Piperacillin/Tazobactam in Adults With Hospital-acquired or Ventilator-associated Bacterial Pneumonia (RESTORE-IMI 2 Study). Clin Infect Dis. 2020 Aug 12:ciaa803. doi: 10.1093/cid/ciaa803. Epub ahead of print. PMID: 32785589. 17: Shayan M, Elyasi S. Cilastatin as a protective agent against drug-induced nephrotoxicity: a literature review. Expert Opin Drug Saf. 2020 Aug;19(8):999-1010. doi: 10.1080/14740338.2020.1796967. Epub 2020 Jul 23. PMID: 32666842. 18: Ghazi IM, El Nekidy WS, Asay R, Fimognari P, Knarr A, Awad M. Correction: Simultaneous administration of imipenem/cilastatin/relebactam with selected intravenous antimicrobials, a stewardship approach. PLoS One. 2020 Jun 24;15(6):e0235405. doi: 10.1371/journal.pone.0235405. Erratum for: PLoS One. 2020 May 18;15(5):e0233335. PMID: 32579614; PMCID: PMC7313957. 19: Hong YA, Jung SY, Yang KJ, Im DS, Jeong KH, Park CW, Hwang HS. Cilastatin Preconditioning Attenuates Renal Ischemia-Reperfusion Injury via Hypoxia Inducible Factor-1α Activation. Int J Mol Sci. 2020 May 19;21(10):3583. doi: 10.3390/ijms21103583. PMID: 32438631; PMCID: PMC7279043. 20: Ghazi IM, El Nekidy WS, Asay R, Fimognari P, Knarr A, Awad M. Simultaneous administration of imipenem/cilastatin/relebactam with selected intravenous antimicrobials, a stewardship approach. PLoS One. 2020 May 18;15(5):e0233335. doi: 10.1371/journal.pone.0233335. Erratum in: PLoS One. 2020 Jun 24;15(6):e0235405. PMID: 32421696; PMCID: PMC7233540.