Solithromycin

Biological Activity

Antibacterial Solithromycin binds to the large 50S subunit of the ribosome and inhibits protein biosynthesis. The mean 50% inhibitory concentrations (IC50s) for Solithromycin inhibition of cell viability, protein synthesis, and growth rate were 7.5, 40, and 125 ng/ml for Streptococcus pneumoniae,Staphylococcus aureus, and Haemophilus influenzae, respectively.

Protocol

Cell Experiment
Cell lines	S. aureus cells
Preparation method	For S. pneumoniae, 12 9-ml cultures of cells comprised of one control set and one set with solithromycin at 7.5 ng/ml were grown to a Klett reading of 15.
Concentrations	7.5 ng/ml
Incubation time	15-min

Animal Experiment
Animal models	donor mic
Formulation	DMSO
Dosages	100 mg/kg
Administration	i.v.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information

References

Solithromycin inhibition of protein synthesis and ribosome biogenesis in Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae.
Rodgers W, et al. Antimicrob Agents Chemother. 2013 Apr;57(4):1632-7. PMID: 23318809.

In vitro and in vivo activity of solithromycin (CEM-101) against Plasmodium species.
Wittlin S, et al. Antimicrob Agents Chemother. 2012 Feb;56(2):703-7. PMID: 22083475.