Grepafloxacin (OPC-17116) is an orally bioactive fluoroquinolone antibiotic (antibiotic) with potent activity against community-acquired respiratory pathogens including Streptococcus pneumoniae. Grepafloxacin has high tissue penetration and good pharmacodynamic properties.

Physicochemical Properties

Molecular Formula	C19H22N3O3F
Molecular Weight	359.39
Exact Mass	359.165
CAS #	119914-60-2
Related CAS #	Grepafloxacin hydrochloride;161967-81-3
PubChem CID	72474
Appearance	Typically exists as solid at room temperature
Density	1.366
Boiling Point	610ºC at 760mmHg
Melting Point	189-192ºC
Flash Point	322.7ºC
LogP	2.674
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	3
Heavy Atom Count	26
Complexity	636
Defined Atom Stereocenter Count	0
SMILES	CC1CN(CCN1)C2=C(C(=C3C(=C2)N(C=C(C3=O)C(=O)O)C4CC4)C)F
InChi Key	AIJTTZAVMXIJGM-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H22FN3O3/c1-10-8-22(6-5-21-10)15-7-14-16(11(2)17(15)20)18(24)13(19(25)26)9-23(14)12-3-4-12/h7,9-10,12,21H,3-6,8H2,1-2H3,(H,25,26)
Chemical Name	1-cyclopropyl-6-fluoro-5-methyl-7-(3-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid
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
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

Targets	Quinolone
ln Vitro	OPC-17116, grepafloxacin, exhibits an antibiotic activity of < 0.006 mg/L for E. coli strain [14–21 days] with a MIC value of 0–1 mg/L. The antibacterial activity of grepafloxacin (0–1 mg/L; 3 h) against mycobacteria in macrophages is demonstrated by a MIC value of 0.5 mg/L for M. avium[1]. High in vivo efficacy against experimental systemic infections induced by the investigated Gram-positive and -negative bacteria is demonstrated by grepafloxacin, which also has strong in vitro antibacterial activity against Gram-positive bacteria such Streptococcus pneumoniae[4].
ln Vivo	In terms of phototoxicity, grepafloxacin (OPC-17116; 200 mg/kg; po; Balb/c mice) exhibits a good safety profile[2]. In both intranasal (IN) and intravenous (IV) Mycobacterium avium infection models, grepafloxacin (25–200 mg/kg; po; 5 days/week for 4 weeks; female C57BL6/J-Lyst bg-J/ mice/beige mice) exhibits modest activities[3].
Animal Protocol	Animal/Disease Models: Female balb/c (Bagg ALBino) mouse: (5-6 weeks)[2] Doses: 200 mg/kg Route of Administration: Oral administration; once Experimental Results: Had mild and short-lived erythema and no changed auricular thickness. Animal/Disease Models: Female C57BL6/J-Lyst bg-J/ mice/beige mice with mycobacterium avium infection[3] Doses: 25, 50, 100, and 200 mg/kg Route of Administration: Oral administration; 5 days/week for 4 weeks Experimental Results: Had bactericidal activity and limited the growth of the bacteria.
ADME/Pharmacokinetics	Absorption, Distribution and Excretion Rapidly and extensively absorbed following oral administration. The absolute bioavailability is approximately 70%. Metabolism / Metabolites Primarily hepatic via CYP1A2 and CYP3A4. The major metabolite is a glucuronide conjugate; minor metabolites include sulfate conjugates and oxidative metabolites. The oxidative metabolites are formed mainly by the cytochrome P450 enzyme CYP1A2, while the cytochrome P450 enzyme CYP3A4 plays a minor role. The nonconjugated metabolites have little antimicrobial activity compared with the parent drug, and the conjugated metabolites have no antimicrobial activity Biological Half-Life 15 ± 3 hours
Toxicity/Toxicokinetics	Protein Binding 50%
References	[1]. Vacher S, et, al. Comparative antimycobacterial activities of ofloxacin, ciprofloxacin and grepafloxacin. J Antimicrob Chemother. 1999 Nov;44(5):647-52. [2]. Owen K. Comparative grepafloxacin phototoxicity in mouse skin. J Antimicrob Chemother. 1998 Aug;42(2):261-4. [3]. Cynamon MH, et, al. The activity of grepafloxacin in two murine models of Mycobacterium avium infection. J Infect Chemother. 2004 Jun;10(3):185-8. [4]. Miyamoto H, et al. Synthesis and biological properties of substituted 1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylic acids. Bioorg Med Chem. 1995;3(12):1699-1706.
Additional Infomation	Grepafloxacin is a member of quinolines, a quinolone antibiotic and a fluoroquinolone antibiotic. Grepafloxacin is an oral broad-spectrum quinoline antibacterial agent used to treat bacterial infections. Due to the QTc-prolonging potential, as indicated by the changes in the QT interval on the electrocardiogram, and the risk for cardiovascular adverse events, grepafloxacin was withdrawn in the United States. Drug Indication For treatment of adults with mild to moderate infections caused by susceptible strains of Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis. Mechanism of Action Grepafloxacin exerts its antibacterial activity by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV, essential enzymes for duplication, transcription, and repair of bacterial DNA. Pharmacodynamics Grepafloxacin has in vitro activity against a wide range of gram-positive and gram-negative aerobic microorganisms, as well as some atypical microorganisms.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7825 mL	13.9125 mL	27.8249 mL
	5 mM	0.5565 mL	2.7825 mL	5.5650 mL
	10 mM	0.2782 mL	1.3912 mL	2.7825 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.