Zifanocycline (KBP-7072) is a semisynthetic third-generation aminomethylcycline antibiotic that can inhibit the normal function of bacterial ribosomes. Zifanocycline displays a broad-spectrum in vitro anti-bacterial effect against Gram-positive (Gram+) and Gram-negative (Gram+) bacteria such as many multidrug-resistant pathogens. Zifanocycline is available by mouth and by injection. Zifanocycline is indicated for the study of acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, and complicated intra-abdominal infections.

Physicochemical Properties

Molecular Formula	C29H36N4O7
Molecular Weight	552.618747711182
Exact Mass	552.258
CAS #	1420294-56-9
Related CAS #	Zifanocycline TFA
PubChem CID	71243332
Appearance	Typically exists as solid at room temperature
LogP	1.6
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	5
Heavy Atom Count	40
Complexity	1200
Defined Atom Stereocenter Count	4
SMILES	CN(C)[C@H]1[C@@H]2C[C@@H]3CC4=C(C=C(C(=C4C(=C3C(=O)[C@@]2(C(=C(C1=O)C(=O)N)O)O)O)O)CN5CC6CC6C5)N(C)C
InChi Key	LBKXOQRVWDAQSX-OMBSCLNISA-N
InChi Code	InChI=1S/C29H36N4O7/c1-31(2)18-8-15(11-33-9-13-5-14(13)10-33)23(34)20-16(18)6-12-7-17-22(32(3)4)25(36)21(28(30)39)27(38)29(17,40)26(37)19(12)24(20)35/h8,12-14,17,22,34-35,38,40H,5-7,9-11H2,1-4H3,(H2,30,39)/t12-,13?,14?,17-,22-,29-/m0/s1
Chemical Name	(4S,4aS,5aR,12aR)-9-(3-azabicyclo[3.1.0]hexan-3-ylmethyl)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide
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

ln Vitro	Zifanocycline (KBP-7072) exhibits minimum inhibitory concentration (MIC90) values of less than 1 μg/ml against several pathogens, encompassing both common and uncommon pathogens linked to community-acquired bacterial pneumonia (CABP)[1].
ln Vivo	KBP-7072 showed a linear PK profile in Sprague-Dawley (SD) rats, beagle dogs, and CD-1 mice following the administration of single oral, IV, and multiple oral doses. Between 12% and 32% of the oral bioavailability was found. There was a range of 0.5 to 4 hours for the mean time to maximum concentration (T max) and roughly 6 to 11 hours for the mean half-life. When oral dosages were given to fed animals, the maximum plasma concentration (C max) and the area under the concentration-time curve (AUC) were much lower than when dosing was done on fasting animals. KBP-7072's mean bound fractions in mouse, rat, dog, monkey, and human plasma were, respectively, 77.5%, 69.8%, 64.5%, 69.3%, and 69.2%[1]. When used against certain methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) S. bacteria, KBP-7072 demonstrates dose-dependent, strong efficacy. aureus strains in a neutropenic murine pneumonia infection model within the dose range (0.25 to 64 mg/kg/6 h) that was investigated[2].
References	[1]. Tan X, et al. Nonclinical Pharmacokinetics, Protein Binding, and Elimination of KBP-7072, an Aminomethylcycline Antibiotic, in Animal Models. Antimicrob Agents Chemother. 2020;64(6):e00488-20. Published 2020 May 21. [2]. Lepak AJ, et al. Pharmacokinetic/Pharmacodynamic Evaluation of a Novel Aminomethylcycline Antibiotic, KBP-7072, in the Neutropenic Murine Pneumonia Model against Staphylococcus aureus and Streptococcus pneumoniae. Antimicrob Agents Chemother. 2019;63(3):e02404-18. Published 2019 Feb 26.

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	1.8096 mL	9.0478 mL	18.0956 mL
	5 mM	0.3619 mL	1.8096 mL	3.6191 mL
	10 mM	0.1810 mL	0.9048 mL	1.8096 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.