Solithromycin
Encyclopedia
Solithromycin is a novel ketolide antibiotic
undergoing clinical development for the treatment of community acquired pneumonia (CAP) and other infections. It is expected to be the first macrolide
antibiotic available in intravenous
, oral, and pediatric suspension formulations in over 20 years.
Solithromycin exhibits excellent in vitro
activity against a broad spectrum of Gram-positive respiratory tract pathogen
s, including macrolide-resistant strains. Solithromycin has activity against a wide variety of pathogens and further research is being conducted for other infection
s.
May 2011 : Solithromycin is in a Phase 2 clinical trial for serious community-acquired bacterial pneumonia (CABP) and in a Phase 1 clinical trial with an intravenous formulation.
Sept 2011 : Encouraging results from the phase 2 clinical trial versus levofloxacin
.
studies have shown that solithromycin, the first fluoroketolide in clinical development, has a third region of interactions with the bacterial ribosome, as compared with two binding sites for other ketolides.
The only currently marketed ketolide, telithromycin
, suffers from rare, but serious side effects
. Recent studies have shown this to be likely due to the presence of the pyridine
-imidazole
group of the telithromycin side chain acting as an antagonist towards various nicotinic acetylcholine receptor
s. Since solithromycin, like azithromycin
and clarithromycin
, lacks this chemical moiety, it is not expected to cause the adverse events seen with Ketek (telithromycin).
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
undergoing clinical development for the treatment of community acquired pneumonia (CAP) and other infections. It is expected to be the first macrolide
Macrolide
The macrolides are a group of drugs whose activity stems from the presence of a macrolide ring, a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered...
antibiotic available in intravenous
Intravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
, oral, and pediatric suspension formulations in over 20 years.
Solithromycin exhibits excellent in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
activity against a broad spectrum of Gram-positive respiratory tract pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
s, including macrolide-resistant strains. Solithromycin has activity against a wide variety of pathogens and further research is being conducted for other infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s.
May 2011 : Solithromycin is in a Phase 2 clinical trial for serious community-acquired bacterial pneumonia (CABP) and in a Phase 1 clinical trial with an intravenous formulation.
Sept 2011 : Encouraging results from the phase 2 clinical trial versus levofloxacin
Levofloxacin
Levofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class and is used to treat severe or life-threatening bacterial infections or bacterial infections that have failed to respond to other antibiotic classes. It is sold under various brand names, such as Levaquin and...
.
Structure
X-ray crystallographyX-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
studies have shown that solithromycin, the first fluoroketolide in clinical development, has a third region of interactions with the bacterial ribosome, as compared with two binding sites for other ketolides.
The only currently marketed ketolide, telithromycin
Telithromycin
Telithromycin is the first ketolide antibiotic to enter clinical use. It is used to treat mild to moderate respiratory infections. Telithromycin is sold under the brand name of Ketek....
, suffers from rare, but serious side effects
Side effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequences of the use of a drug.Occasionally, drugs are...
. Recent studies have shown this to be likely due to the presence of the pyridine
Pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one C-H group replaced by a nitrogen atom...
-imidazole
Imidazole
Imidazole is an organic compound with the formula C3H4N2. This aromatic heterocyclic is a diazole and is classified as an alkaloid. Imidazole refers to the parent compound, whereas imidazoles are a class of heterocycles with similar ring structure, but varying substituents...
group of the telithromycin side chain acting as an antagonist towards various nicotinic acetylcholine receptor
Nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the postsynaptic side of the neuromuscular junction...
s. Since solithromycin, like azithromycin
Azithromycin
Azithromycin is an azalide, a subclass of macrolide antibiotics. Azithromycin is one of the world's best-selling antibiotics...
and clarithromycin
Clarithromycin
Clarithromycin is a macrolide antibiotic used to treat pharyngitis, tonsillitis, acute maxillary sinusitis, acute bacterial exacerbation of chronic bronchitis, pneumonia , skin and skin structure infections...
, lacks this chemical moiety, it is not expected to cause the adverse events seen with Ketek (telithromycin).