Nacubactam (OP-0595; RG-6080, FPI-1459) is a novel, non-β-lactam and potent beta-lactamase inhibitor with antibacterial activity against class A and class C β-lactamases. Acting as an inhibitor of penicillin binding protein (PBP) which is involved in the cross-linking of the peptidoglycan layer of the cell wall, which is weakened, and this leads to osmotic rupture.

Physicochemical Properties

Molecular Formula	C9H16N4O7S
Molecular Weight	324.311
Exact Mass	324.074
Elemental Analysis	C, 33.33; H, 4.97; N, 17.28; O, 34.53; S, 9.89
CAS #	1452458-86-4
Related CAS #	2007923-17-1 (hydrate);1452458-86-4 (free acid);
PubChem CID	73386748
Appearance	Off-white to beige solid powder
LogP	-4.6
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	6
Heavy Atom Count	21
Complexity	519
Defined Atom Stereocenter Count	2
SMILES	C1C[C@H](N2C[C@@H]1N(C2=O)OS(=O)(=O)O)C(=O)NOCCN
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
Chemical Name	(1R,2S,5R)-2-((2-aminoethoxy)carbamoyl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl hydrogen sulfate
Synonyms	RG-6080; RG 6080; RG6080; FPI-1459; FPI 1459; FPI1459; OP-0595; OP 0595; OP0595; Nacubactam;
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

References

[1]. In Vivo Efficacy of Meropenem with a Novel Non-β-Lactam-β-Lactamase Inhibitor, Nacubactam, against Gram-Negative Organisms Exhibiting Various Resistance Mechanisms in a Murine Complicated Urinary Tract Infection Model. Antimicrob Agents Chemother. 2018 Aug 27;62(9). [2]. Activity of OP0595/β-lactam combinations against Gram-negative bacteria with extended-spectrum, AmpC and carbapenem-hydrolysing β-lactamases. J Antimicrob Chemother. 2015 Nov;70(11):3032-41.

Additional Infomation

Nacubactam is under investigation in clinical trial NCT03174795 (A Study to Investigate the Pharmacokinetics of RO7079901 and Meropenem in Participants With a Complicated Urinary Tract Infection).

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~770.87 mM) H2O : ~50 mg/mL (~154.17 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.41 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.41 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (6.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 100 mg/mL (308.35 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.0835 mL	15.4173 mL	30.8347 mL
	5 mM	0.6167 mL	3.0835 mL	6.1669 mL
	10 mM	0.3083 mL	1.5417 mL	3.0835 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.