WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H319570
CAS#: 1174018-99-5 (free acid)
Description: Relebactam, also known as MK-7655, a potent and selective β-lactamase inhibitor. At a concentration of 4 mg/L, MK-7655 reduced imipenem MICs for Enterobacteriaceae with KPC carbapenemases from 16-64 mg/L to 0.12-1 mg/L. MK-7655 potentiated imipenem against Enterobacteriaceae with KPC carbapenemases or combinations of β-lactamase and impermeability, but not those with metallo-carbapenemases. It augmented the activity of imipenem against P. aeruginosa in general and OprD mutants in particular.
Hodoodo Cat#: H319570
Name: Relebactam
CAS#: 1174018-99-5 (free acid)
Chemical Formula: C12H20N4O6S
Exact Mass: 348.11
Molecular Weight: 348.370
Elemental Analysis: 41.37; H, 5.79; N, 16.08; O, 27.55; S, 9.20
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:
| 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 | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 70.0 | 200.94 | |
| Water | 71.0 | 203.81 |
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: | 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. |
| 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.
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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.
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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.
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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.
