Modithromycin is a potent bicyclolide agent with antibacterial activity.

Physicochemical Properties

Molecular Formula	C43H64N6O11
Molecular Weight	841.001860000001
Exact Mass	840.463
Elemental Analysis	C, 61.41; H, 7.67; N, 9.99; O, 20.93
CAS #	736992-12-4
PubChem CID	9875927
Appearance	Solid powder
LogP	3.6
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	15
Rotatable Bond Count	8
Heavy Atom Count	60
Complexity	1550
Defined Atom Stereocenter Count	13
SMILES	CC[C@@H]1[C@@]([C@H]2[C@H](C(=NC(=O)C)[C@@H](C[C@]([C@@H]([C@H](C(=O)[C@H](C(=O)O1)C)C)O[C@H]3[C@@H]([C@H](C[C@H](O3)C)N(C)C)O)(OC/C(=N/OCC4=CN=C(C=C4)N5C=CC=N5)/CO2)C)C)C)(C)O
InChi Key	WLGSYOKBEDVHQB-XSKCQLPHSA-N
InChi Code	InChI=1S/C43H64N6O11/c1-12-33-43(9,54)39-26(4)35(46-29(7)50)24(2)19-42(8,56-23-31(22-55-39)47-57-21-30-14-15-34(44-20-30)49-17-13-16-45-49)38(27(5)36(51)28(6)40(53)59-33)60-41-37(52)32(48(10)11)18-25(3)58-41/h13-17,20,24-28,32-33,37-39,41,52,54H,12,18-19,21-23H2,1-11H3/b46-35+,47-31+/t24-,25-,26+,27+,28-,32+,33-,37-,38-,39-,41+,42-,43-/m1/s1
Chemical Name	N-((1R,2R,3R,6R,8R,9R,10R,13E,16S,17E,18R)-13-(((6-(1H-pyrazol-1-yl)pyridin-3-yl)methoxy)imino)-9-(((2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-3-ethyl-2-hydroxy-2,6,8,10,16,18-hexamethyl-5,7-dioxo-4,11,15-trioxabicyclo[8.5.4]nonadecan-17-ylidene)acetamide
Synonyms	S-013420; S 013420; Modithromycin
HS Tariff Code	2934.99.03.00
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	Modithromycin is a is a ketolide (macrolide) antibacterial. Ketolides are erythromycin derivatives with a broad-spectrum of antibacterial activity. New antimicrobials are essential to prevent gonorrhoea becoming an untreatable infection. Herein, the in vitro activities of the novel bicyclolides modithromycin (EDP-420, EP-013420, S-013420) and EDP-322 against Neisseria gonorrhoeae strains were investigated and compared with antimicrobials currently or previously recommended for treatment of gonorrhoea[1].
Enzyme Assay	Modithromycin and EDP-322 exhibited high levels of in vitro activities against N. gonorrhoeae, including isolates resistant to azithromycin, cefixime, ceftriaxone, spectinomycin, ampicillin, tetracycline and ciprofloxacin. However, some cross-resistance with high-level azithromycin resistance (MIC = 4096 mg/L) was observed. Modithromycin and EDP-322 could be effective options for treatment of gonorrhoea, particularly for cases resistant to extended-spectrum cephalosporins and as a part of an antimicrobial combination therapy regimen. Nevertheless, it is important to detail the in vitro selection, in vivo emergence and mechanisms of resistance, pharmacokinetics/pharmacodynamics in humans and optimal dosing, and perform appropriate randomized controlled clinical trials[1].
Cell Assay	MICs (mg/L) were determined using an agar dilution method (modithromycin and EDP-322) or Etest (seven antimicrobials) for a large geographically, temporally and genetically diverse collection of clinical N. gonorrhoeae isolates (n = 225) and international reference strains (n = 29), including diverse MDR and XDR isolates [1].
References	[1]. In vitro activities of the novel bicyclolides modithromycin (EDP-420, EP-013420, S-013420) and EDP-322 against MDR clinical Neisseria gonorrhoeae isolates and international reference strains. J Antimicrob Chemother . 2015 Jan;70(1):173-7. doi: 10.1093/jac/dku344.
Additional Infomation	Modithromycin is under investigation in clinical trial NCT00270517 (Comparative Study of EDP-420 Versus Another Antibiotic in the Treatment of Community Acquired Pneumonia).

Solubility Data

Solubility (In Vitro)

DMSO: > 10 mM

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	1.1891 mL	5.9453 mL	11.8906 mL
	5 mM	0.2378 mL	1.1891 mL	2.3781 mL
	10 mM	0.1189 mL	0.5945 mL	1.1891 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.