Relebactam | CAS#1174018-99-5 | β-lactamase inhibitor

MedKoo Cat#: 319570 | Name: Relebactam

Description:

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

Relebactam, also known as MK-7655, is a non-β-lactam β-lactamase inhibitor that primarily targets class A (including KPC) and class C (AmpC) β-lactamases, thereby restoring the activity of β-lactam antibiotics such as imipenem. In combination with imipenem-cilastatin (marketed as Recarbrio), relebactam has shown potent in vitro activity against multidrug-resistant Gram-negative pathogens, particularly carbapenem-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa. Minimum inhibitory concentration (MIC) data indicate that imipenem-relebactam reduces MIC values significantly compared to imipenem alone; for instance, the MIC₉₀ against P. aeruginosa is often ≤4 µg/mL versus >16 µg/mL for imipenem alone.

Chemical Structure

Relebactam

CAS#1174018-99-5 (free acid)

Theoretical Analysis

MedKoo Cat#: 319570

Name: Relebactam

CAS#: 1174018-99-5 (free acid)

Chemical Formula: C12H20N4O6S

Exact Mass: 348.1104

Molecular Weight: 348.37

Elemental Analysis: 41.37; H, 5.79; N, 16.08; O, 27.55; S, 9.20

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 450.00	Ready to ship
50mg	USD 750.00	Ready to ship
100mg	USD 1,350.00	Ready to ship

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Related CAS #

1174020-13-3 (hydrate) 1174018-99-5 (free acid) 1502858-91-4 (sodium)

Synonym

MK-7655; MK 7655; MK7655; Relebactam;

IUPAC/Chemical Name

(1R,2S,5R)-7-oxo-2-(piperidin-4-ylcarbamoyl)-1,6-diazabicyclo[3.2.1]octan-6-yl hydrogen sulfate

InChi Key

SMOBCLHAZXOKDQ-ZJUUUORDSA-N

InChi Code

InChI=1S/C12H20N4O6S/c17-11(14-8-3-5-13-6-4-8)10-2-1-9-7-15(10)12(18)16(9)22-23(19,20)21/h8-10,13H,1-7H2,(H,14,17)(H,19,20,21)/t9-,10+/m1/s1

SMILES Code

O=S(O)(ON1[C@]2([H])CC[C@@H](C(NC3CCNCC3)=O)[N@@](C2)C1=O)=O

Appearance

White to off-white 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 and water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO or water

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

Certificate of Analysis

View CoA: current batch, Lot#A7N05B30

QC Data

View QC data: current batch, Lot#A7N05B30

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Relebactam is a β-lactamase inhibitor that inhibits hydrolysis of nitrocefin by KPC-2 β-lactamase from K. pneumoniae and AmpC β-lactamase from P. aeruginosa (IC50s = 210 and 465 nM, respectively). Relebactam restores imipenem-susceptibility in imipenem-resistant K. pneumoniae and P. aeruginosa when used at concentrations of 12.5 and 4.7 μM, respectively. Relebactam also restores imipenem sensitivity to resistant clinical isolates of P. aeruginosa and K. pneumoniae (MIC50s = 0.25-2 and 8-16 μM in the presence and absence of relebactam, respectively), but not A. baumannii. In vivo, relebactam (48.9 mg/kg per day) produces a bacteriostatic effect in mouse thigh models of K. pneumoniae and P. aeruginosa infection when administered with imipenem and cilastatin.

In vitro activity:

(MK-7655) inhibited both class A and C β-lactamases in vitro. It effectively restored imipenem's activity against imipenem-resistant Pseudomonas and Klebsiella strains at clinically achievable concentrations. Reference: Bioorg Med Chem Lett. 2014 Feb 1;24(3):780-5. https://pubmed.ncbi.nlm.nih.gov/24433862/

In vivo activity:

This phase 3 clinical trial found that imipenem combined with relebactam is a therapeutic option in hospital-acquired pneumonia and ventilator-associated pneumonia at approved dosages of imipenem 500 mg, cilastatin 500 mg and relebactam 250 mg once every 6h, by an IV infusion over 30 min. Reference: Rev Esp Quimioter. 2022 Apr;35 Suppl 1(Suppl 1):46-49. https://pubmed.ncbi.nlm.nih.gov/35488826/

	Solvent	mg/mL	mM
Solubility
	DMSO	10.0	28.71
	DMF	1.0	2.87

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 348.37 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. Lob SH, Hackel MA, Kazmierczak KM, Young K, Motyl MR, Karlowsky JA, Sahm DF. In Vitro Activity of Imipenem-Relebactam against Gram-Negative ESKAPE Pathogens Isolated by Clinical Laboratories in the United States in 2015 (Results from the SMART Global Surveillance Program). Antimicrob Agents Chemother. 2017 May 24;61(6):e02209-16. doi: 10.1128/AAC.02209-16. PMID: 28320716; PMCID: PMC5444184. 2. Blizzard TA, Chen H, Kim S, Wu J, Bodner R, Gude C, Imbriglio J, Young K, Park YW, Ogawa A, Raghoobar S, Hairston N, Painter RE, Wisniewski D, Scapin G, Fitzgerald P, Sharma N, Lu J, Ha S, Hermes J, Hammond ML. Discovery of MK-7655, a β-lactamase inhibitor for combination with Primaxin®. Bioorg Med Chem Lett. 2014 Feb 1;24(3):780-5. doi: 10.1016/j.bmcl.2013.12.101. Epub 2014 Jan 3. PMID: 24433862. 3. Girón RM, Ibáñez A, Gómez-Punter RM, Alarcón T. New evidence in severe pneumonia: imipenem/ cilastatin/relebactam. Rev Esp Quimioter. 2022 Apr;35 Suppl 1(Suppl 1):46-49. doi: 10.37201/req/s01.11.2022. Epub 2022 Apr 22. PMID: 35488826; PMCID: PMC9106194. 4. 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.

In vitro protocol:

In vivo protocol:

1. Girón RM, Ibáñez A, Gómez-Punter RM, Alarcón T. New evidence in severe pneumonia: imipenem/ cilastatin/relebactam. Rev Esp Quimioter. 2022 Apr;35 Suppl 1(Suppl 1):46-49. doi: 10.37201/req/s01.11.2022. Epub 2022 Apr 22. PMID: 35488826; PMCID: PMC9106194. 2. 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.

1: Chung JYL, Meng D, Shevlin M, Gudipati V, Chen Q, Liu Y, Lam YH, Dumas A, Scott J, Tu Q, Xu F. Diastereoselective FeCl3·6H2O / NaBH4 Reduction of Oxime Ether for the Synthesis of β-Lactamase Inhibitor Relebactam. J Org Chem. 2019 Dec 18. doi: 10.1021/acs.joc.9b02948. [Epub ahead of print] PubMed PMID: 31850754. 2: Fraile-Ribot P, Zamorano L, Orellana R, Barrio-Tofiño ED, Sánchez-Diener I, Cortes-Lara S, López-Causapé C, Cabot G, Bou G, Martínez-Martínez L, Oliver A; GEMARA-SEIMC/REIPI Pseudomonas study Group. Activity of imipenem/relebactam against a large collection of Pseudomonas aeruginosa clinical isolates and isogenic β-lactam resistant mutants. Antimicrob Agents Chemother. 2019 Nov 18. pii: AAC.02165-19. doi: 10.1128/AAC.02165-19. [Epub ahead of print] PubMed PMID: 31740559. 3: Karlowsky JA, Lob SH, Kazmierczak KM, Young K, Motyl MR, Sahm DF. In vitro activity of imipenem-relebactam and key β-lactam agents against Gram-negative bacilli isolated from lower respiratory tract infection samples of intensive care unit patients - SMART Surveillance United States 2015-2017. Int J Antimicrob Agents. 2019 Nov 5. pii: S0924-8579(19)30302-4. doi: 10.1016/j.ijantimicag.2019.10.022. [Epub ahead of print] PubMed PMID: 31704217. 4: Karlowsky JA, Lob SH, Kazmierczak KM, Young K, Motyl MR, Sahm DF. In vitro activity of imipenem-relebactam against Enterobacteriaceae and Pseudomonas aeruginosa isolated from intraabdominal and urinary tract infection samples - SMART Surveillance United States 2015-2017. J Glob Antimicrob Resist. 2019 Nov 4. pii: S2213-7165(19)30290-5. doi: 10.1016/j.jgar.2019.10.028. [Epub ahead of print] PubMed PMID: 31698105. 5: Le Run E, Atze H, Arthur M, Mainardi JL. Impact of relebactam-mediated inhibition of Mycobacterium abscessus BlaMab β-lactamase on the in vitro and intracellular efficacy of imipenem. J Antimicrob Chemother. 2019 Oct 21. pii: dkz433. doi: 10.1093/jac/dkz433. [Epub ahead of print] PubMed PMID: 31637424. 6: Bhagunde P, Patel P, Lala M, Watson K, Copalu W, Xu M, Kulkarni P, Young K, Rizk ML. Population Pharmacokinetic Analysis for Imipenem-Relebactam in Healthy Volunteers and Patients With Bacterial Infections. CPT Pharmacometrics Syst Pharmacol. 2019 Oct;8(10):748-758. doi: 10.1002/psp4.12462. Epub 2019 Oct 4. PubMed PMID: 31508899; PubMed Central PMCID: PMC6813166. 7: Bhagunde P, Zhang Z, Racine F, Carr D, Wu J, Young K, Rizk ML. A translational pharmacokinetic/pharmacodynamic model to characterize bacterial kill in the presence of imipenem-relebactam. Int J Infect Dis. 2019 Dec;89:55-61. doi: 10.1016/j.ijid.2019.08.026. Epub 2019 Aug 31. PubMed PMID: 31479762. 8: Carpenter J, Neidig N, Campbell A, Thornsberry T, Truex T, Fortney T, Zhang Y, Bush K. Activity of imipenem/relebactam against carbapenemase-producing Enterobacteriaceae with high colistin resistance. J Antimicrob Chemother. 2019 Nov 1;74(11):3260-3263. doi: 10.1093/jac/dkz354. PubMed PMID: 31430370. 9: Motsch J, Murta de Oliveira C, Stus V, Köksal I, Lyulko O, Boucher HW, Kaye KS, File TM, Brown ML, Khan I, Du J, Joeng HK, Tipping RW, Aggrey A, Young K, Kartsonis NA, Butterton JR, Paschke A. RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections. Clin Infect Dis. 2019 Aug 10. pii: ciz530. doi: 10.1093/cid/ciz530. [Epub ahead of print] PubMed PMID: 31400759. 10: Tooke CL, Hinchliffe P, Lang PA, Mulholland AJ, Brem J, Schofield CJ, Spencer J. Molecular Basis of Class A β-Lactamase Inhibition by Relebactam. Antimicrob Agents Chemother. 2019 Sep 23;63(10). pii: e00564-19. doi: 10.1128/AAC.00564-19. Print 2019 Oct. PubMed PMID: 31383664; PubMed Central PMCID: PMC6761529. 11: Kulengowski B, Burgess DS. Imipenem/relebactam activity compared to other antimicrobials against non-MBL-producing carbapenem-resistant Enterobacteriaceae from an academic medical center. Pathog Dis. 2019 Jun 1;77(4). pii: ftz040. doi: 10.1093/femspd/ftz040. PubMed PMID: 31365075. 12: Chen Y, Xu M, Xu W, Song H, Hu L, Xue S, Zhang S, Qian X, Xie H. Highly selective and wash-free visualization of resistant bacteria with a relebactam-derived fluorogenic probe. Chem Commun (Camb). 2019 Aug 28;55(67):9919-9922. doi: 10.1039/c9cc04533c. Epub 2019 Jul 22. PubMed PMID: 31328197. 13: Young K, Painter RE, Raghoobar SL, Hairston NN, Racine F, Wisniewski D, Balibar CJ, Villafania A, Zhang R, Sahm DF, Blizzard T, Murgolo N, Hammond ML, Motyl MR. In vitro studies evaluating the activity of imipenem in combination with relebactam against Pseudomonas aeruginosa. BMC Microbiol. 2019 Jul 4;19(1):150. doi: 10.1186/s12866-019-1522-7. PubMed PMID: 31272373; PubMed Central PMCID: PMC6610938. 14: Asempa TE, Nicolau DP, Kuti JL. In Vitro Activity of Imipenem-Relebactam Alone or in Combination with Amikacin or Colistin against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2019 Aug 23;63(9). pii: e00997-19. doi: 10.1128/AAC.00997-19. Print 2019 Sep. PubMed PMID: 31262769; PubMed Central PMCID: PMC6709505. 15: Canver MC, Satlin MJ, Westblade LF, Kreiswirth BN, Chen L, Robertson A, Fauntleroy K, La Spina M, Callan K, Jenkins SG. Activity of Imipenem-Relebactam and Comparator Agents against Genetically Characterized Isolates of Carbapenem-Resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2019 Aug 23;63(9). pii: e00672-19. doi: 10.1128/AAC.00672-19. Print 2019 Sep. PubMed PMID: 31262761; PubMed Central PMCID: PMC6709495. 16: Noel AR, Bowker KE, Attwood M, MacGowan AP. Antibacterial effect of imipenem/relebactam on aerobic Gram-negative bacilli: in vitro simulations of 7 or 14 day human exposures. J Antimicrob Chemother. 2019 Jul 1;74(7):1945-1951. doi: 10.1093/jac/dkz114. PubMed PMID: 31220257. 17: Karlowsky JA, Lob SH, Young K, Motyl MR, Sahm DF. Activity of imipenem-relebactam against multidrug-resistant Pseudomonas aeruginosa from the United States - SMART 2015-2017. Diagn Microbiol Infect Dis. 2019 Oct;95(2):212-215. doi: 10.1016/j.diagmicrobio.2019.05.001. Epub 2019 May 8. PubMed PMID: 31174995. 18: Lob SH, Karlowsky JA, Young K, Motyl MR, Hawser S, Kothari ND, Gueny ME, Sahm DF. Activity of imipenem/relebactam against MDR Pseudomonas aeruginosa in Europe: SMART 2015-17. J Antimicrob Chemother. 2019 Aug 1;74(8):2284-2288. doi: 10.1093/jac/dkz191. PubMed PMID: 31086960. 19: Galani I, Souli M, Nafplioti K, Adamou P, Karaiskos I, Giamarellou H, Antoniadou A; Study Collaborators. Correction to: In vitro activity of imipenem-relebactam against non-MBL carbapenemase-producing Klebsiella pneumoniae isolated in Greek hospitals in 2015-2016. Eur J Clin Microbiol Infect Dis. 2019 Jun;38(6):1151-1152. doi: 10.1007/s10096-019-03553-8. PubMed PMID: 31037478. 20: Horner C, Mushtaq S, Livermore DM; BSAC Resistance Surveillance Standing Committee . Potentiation of imipenem by relebactam for Pseudomonas aeruginosa from bacteraemia and respiratory infections. J Antimicrob Chemother. 2019 Jul 1;74(7):1940-1944. doi: 10.1093/jac/dkz133. PubMed PMID: 31032858.

Lang PA, Leissing TM, Page MGP, Schofield CJ, Brem J. Structural Investigations of the Inhibition of Escherichia coli AmpC β-Lactamase by Diazabicyclooctanes. Antimicrob Agents Chemother. 2021 Jan 20;65(2):e02073-20. doi: 10.1128/AAC.02073-20. PMID: 33199391; PMCID: PMC7849013.