Synonym
RG-6080; RG 6080; RG6080; FPI-1459; FPI 1459; FPI1459; OP-0595; OP 0595; OP0595; Nacubactam;
IUPAC/Chemical Name
(1R,2S,5R)-2-((2-aminoethoxy)carbamoyl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl hydrogen sulfate
InChi Key
RSBPYSTVZQAADE-RQJHMYQMSA-N
InChi Code
InChI=1S/C9H16N4O7S/c10-3-4-19-11-8(14)7-2-1-6-5-12(7)9(15)13(6)20-21(16,17)18/h6-7H,1-5,10H2,(H,11,14)(H,16,17,18)/t6-,7+/m1/s1
SMILES Code
O=S(O)(ON1[C@]2([H])CC[C@@H](C(NOCCN)=O)[N@@](C2)C1=O)=O
Appearance
Off-white to beige 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
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
Biological target:
Nacubactam (OP0595 free acid) is a potent non-β-lactam-β-lactamase inhibitor with activity against class A and class C β-lactamases.
In vitro activity:
To assess the functional concentration of OP0595 for use with β-lactam agents, the MICs (the lowest concentration to prevent visible growth after incubation at 35°C for 18 to 20 h) of piperacillin, cefepime, and meropenem in combination with different concentrations of OP0595 were determined against five strains of CTX-M-15-positive E. coli and five strains of KPC-positive K. pneumoniae. The log averages of MICs were plotted as the geometric mean MICs (Fig. 1). For all β-lactam agents, the geometric mean MICs decreased as the OP0595 concentrations increased, regardless of the type of partner β-lactam agent or the bacterial species. In each case, the MIC reached a plateau at 2 to 4 μg/ml of OP0595. These results suggest that a concentration of 4 μg/ml of OP0595 against these strains is sufficient to result in maximal MIC reduction in in vitro studies.
Reference: Antimicrob Agents Chemother. 2016 Apr 22;60(5):3001-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862534/
In vivo activity:
A neutropenic murine model of thigh infection was used to clarify the efficacy of OP0595 alone and in combination with cefepime in vivo. The strains tested were CTX-M-15-positive E. coli MSC20653 and MSC20662 and KPC-positive K. pneumoniae ATCC BAA-1705 and ATCC BAA-1904, which have been confirmed to grow in the thigh of neutropenic Crlj:CD1 (ICR) mice. The viable cell counts of CTX-M-15-positive E. coli MSC20653 or MSC20662 in control mice and in mice after administration of the test compounds are shown in Fig. 3A. The viable cell count in mice treated with cefepime (10 mg/kg) or OP0595 (2.5 mg/kg) was not significantly lower than that in mice treated with vehicle at 23 h after the start of treatment. However, mice in the cefepime-OP0595 groups (5/1.25 mg/kg and 10/2.5 mg/kg) had significantly (P < 0.05) lower bacterial counts than those in the saline vehicle group. Cefepime-OP0595 showed stronger efficacy than cefepime alone against all β-lactamase-positive strains tested, whereas OP0595 alone showed weaker or no efficacy. Taken together, these data indicate that combinational use of OP0595 and a β-lactam agent is important to exert the antimicrobial functions of OP0595.
Reference: Antimicrob Agents Chemother. 2016 Apr 22;60(5):3001-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862534/
|
Solvent |
mg/mL |
mM |
| Solubility |
| Water |
62.5 |
192.72 |
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
324.31
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. Morinaka A, Tsutsumi Y, Yamada K, Takayama Y, Sakakibara S, Takata T, Abe T, Furuuchi T, Inamura S, Sakamaki Y, Tsujii N, Ida T. In vitro and in vivo activities of the diazabicyclooctane OP0595 against AmpC-derepressed Pseudomonas aeruginosa. J Antibiot (Tokyo). 2017 Mar;70(3):246-250. doi: 10.1038/ja.2016.150. Epub 2016 Dec 21. PMID: 27999441.
2. Morinaka A, Tsutsumi Y, Yamada K, Takayama Y, Sakakibara S, Takata T, Abe T, Furuuchi T, Inamura S, Sakamaki Y, Tsujii N, Ida T. In Vitro and In Vivo Activities of OP0595, a New Diazabicyclooctane, against CTX-M-15-Positive Escherichia coli and KPC-Positive Klebsiella pneumoniae. Antimicrob Agents Chemother. 2016 Apr 22;60(5):3001-6. doi: 10.1128/AAC.02704-15. PMID: 26953205; PMCID: PMC4862534.
In vitro protocol:
1. Morinaka A, Tsutsumi Y, Yamada K, Takayama Y, Sakakibara S, Takata T, Abe T, Furuuchi T, Inamura S, Sakamaki Y, Tsujii N, Ida T. In vitro and in vivo activities of the diazabicyclooctane OP0595 against AmpC-derepressed Pseudomonas aeruginosa. J Antibiot (Tokyo). 2017 Mar;70(3):246-250. doi: 10.1038/ja.2016.150. Epub 2016 Dec 21. PMID: 27999441.
2. Morinaka A, Tsutsumi Y, Yamada K, Takayama Y, Sakakibara S, Takata T, Abe T, Furuuchi T, Inamura S, Sakamaki Y, Tsujii N, Ida T. In Vitro and In Vivo Activities of OP0595, a New Diazabicyclooctane, against CTX-M-15-Positive Escherichia coli and KPC-Positive Klebsiella pneumoniae. Antimicrob Agents Chemother. 2016 Apr 22;60(5):3001-6. doi: 10.1128/AAC.02704-15. PMID: 26953205; PMCID: PMC4862534.
In vivo protocol:
1. Morinaka A, Tsutsumi Y, Yamada K, Takayama Y, Sakakibara S, Takata T, Abe T, Furuuchi T, Inamura S, Sakamaki Y, Tsujii N, Ida T. In vitro and in vivo activities of the diazabicyclooctane OP0595 against AmpC-derepressed Pseudomonas aeruginosa. J Antibiot (Tokyo). 2017 Mar;70(3):246-250. doi: 10.1038/ja.2016.150. Epub 2016 Dec 21. PMID: 27999441.
2. Morinaka A, Tsutsumi Y, Yamada K, Takayama Y, Sakakibara S, Takata T, Abe T, Furuuchi T, Inamura S, Sakamaki Y, Tsujii N, Ida T. In Vitro and In Vivo Activities of OP0595, a New Diazabicyclooctane, against CTX-M-15-Positive Escherichia coli and KPC-Positive Klebsiella pneumoniae. Antimicrob Agents Chemother. 2016 Apr 22;60(5):3001-6. doi: 10.1128/AAC.02704-15. PMID: 26953205; PMCID: PMC4862534.
Tell, M. (2015). Clinical Microbiology and Infectious Diseases (ECCMID)-25th European Congress. Copenhagen, Denmark-April 25-28, 2015. Drugs of the Future, 40(6).
Moya, B., Barcelo, I. M., Bhagwat, S., Patel, M., Bou, G., Papp-Wallace, K. M., ... & Oliver, A. (2017). WCK 5107 (zidebactam) and WCK 5153 are novel inhibitors of PBP2 showing potent “β-lactam enhancer” activity against Pseudomonas aeruginosa, including multidrug-resistant metallo-β-lactamase-producing high-risk clones. Antimicrobial agents and chemotherapy, 61(6), 10-1128.
Zerdan, M. B., Al Hassan, S., Shaker, W., El Hajjar, R., Allam, S., Zerdan, M. B., ... & Zeineddine, N. (2022). Carbapenemase inhibitors: updates on developments in 2021. Journal of Clinical Medicine Research, 14(7), 251.
Montravers, P., & Bassetti, M. (2018). The ideal patient profile for new beta-lactam/beta-lactamase inhibitors. Current opinion in infectious diseases, 31(6), 587-593.
