This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Solithromycin
Accession Number
DB09308
Type
Small Molecule
Groups
Investigational
Description

Solithromycin is a ketolide antibiotic undergoing clinical development for the treatment of community-acquired pneumonia (CAP) and other infections.

Structure
Thumb
Synonyms
Not Available
External IDs
CEM 101 / CEM-101 / OP 1068 / OP-1068
Categories
UNII
9U1ETH79CK
CAS number
760981-83-7
Weight
Average: 845.0088
Monoisotopic: 844.474620535
Chemical Formula
C43H65FN6O10
InChI Key
IXXFZUPTQVDPPK-ZAWHAJPISA-N
InChI
InChI=1S/C43H65FN6O10/c1-12-32-43(8)35(50(40(55)60-43)19-14-13-18-49-23-30(46-47-49)28-16-15-17-29(45)21-28)26(4)33(51)24(2)22-41(6,56-11)37(27(5)36(53)42(7,44)39(54)58-32)59-38-34(52)31(48(9)10)20-25(3)57-38/h15-17,21,23-27,31-32,34-35,37-38,52H,12-14,18-20,22,45H2,1-11H3/t24-,25-,26+,27+,31+,32-,34-,35-,37-,38+,41-,42+,43-/m1/s1
IUPAC Name
(3aS,4R,7S,9R,10R,11R,13R,15R,15aR)-1-{4-[4-(3-aminophenyl)-1H-1,2,3-triazol-1-yl]butyl}-10-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-4-ethyl-7-fluoro-11-methoxy-3a,7,9,11,13,15-hexamethyl-tetradecahydro-1H-oxacyclotetradeca[4,3-d][1,3]oxazole-2,6,8,14-tetrone
SMILES
[H][C@]12N(CCCCN3C=C(N=N3)C3=CC(N)=CC=C3)C(=O)O[C@]1(C)[C@@]([H])(CC)OC(=O)[C@@](C)(F)C(=O)[C@]([H])(C)[C@@]([H])(O[C@]1([H])O[C@]([H])(C)C[C@]([H])(N(C)C)[C@@]1([H])O)[C@@](C)(C[C@@]([H])(C)C(=O)[C@]2([H])C)OC

Pharmacology

Indication

Investigated for the treatment of community-acquired pneumonia (CAP).

Pharmacodynamics
Not Available
Mechanism of action
Not Available
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Solithromycin.Approved, Investigational
AcetyldigitoxinThe serum concentration of Acetyldigitoxin can be increased when it is combined with Solithromycin.Approved
AcetyldigoxinThe serum concentration of Acetyldigoxin can be increased when it is combined with Solithromycin.Experimental
AlfentanilThe serum concentration of Alfentanil can be increased when it is combined with Solithromycin.Approved, Illicit
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Solithromycin.Approved, Illicit, Investigational
Ambroxol acefyllinateThe metabolism of Ambroxol acefyllinate can be decreased when combined with Solithromycin.Experimental, Investigational
AminophyllineThe metabolism of Aminophylline can be decreased when combined with Solithromycin.Approved
AtorvastatinThe risk or severity of adverse effects can be increased when Solithromycin is combined with Atorvastatin.Approved
BromocriptineThe serum concentration of Bromocriptine can be increased when it is combined with Solithromycin.Approved, Investigational
BuspironeThe metabolism of Buspirone can be decreased when combined with Solithromycin.Approved, Investigational
CabergolineThe serum concentration of Cabergoline can be increased when it is combined with Solithromycin.Approved
CarbamazepineThe metabolism of Carbamazepine can be decreased when combined with Solithromycin.Approved, Investigational
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Solithromycin.Approved, Investigational, Withdrawn
ClorindioneThe serum concentration of Clorindione can be increased when it is combined with Solithromycin.Experimental
CyclosporineThe metabolism of Cyclosporine can be decreased when combined with Solithromycin.Approved, Investigational, Vet Approved
CymarinThe serum concentration of Cymarin can be increased when it is combined with Solithromycin.Experimental
DeslanosideThe serum concentration of Deslanoside can be increased when it is combined with Solithromycin.Approved
DicoumarolThe serum concentration of Dicoumarol can be increased when it is combined with Solithromycin.Approved
DigitoxinThe serum concentration of Digitoxin can be increased when it is combined with Solithromycin.Approved, Investigational
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Solithromycin.Approved
Digoxin Immune Fab (Ovine)The serum concentration of Digoxin Immune Fab (Ovine) can be increased when it is combined with Solithromycin.Approved
DihydroergotamineThe serum concentration of Dihydroergotamine can be increased when it is combined with Solithromycin.Approved, Investigational
DiphenadioneThe serum concentration of Diphenadione can be increased when it is combined with Solithromycin.Experimental
DisopyramideSolithromycin may increase the QTc-prolonging activities of Disopyramide.Approved
Ergoloid mesylateThe serum concentration of Ergoloid mesylate can be increased when it is combined with Solithromycin.Approved
ErgonovineThe serum concentration of Ergonovine can be increased when it is combined with Solithromycin.Approved
ErgotamineThe serum concentration of Ergotamine can be increased when it is combined with Solithromycin.Approved
EstazolamThe serum concentration of Estazolam can be increased when it is combined with Solithromycin.Approved, Illicit
Ethyl biscoumacetateThe serum concentration of Ethyl biscoumacetate can be increased when it is combined with Solithromycin.Withdrawn
FluindioneThe serum concentration of Fluindione can be increased when it is combined with Solithromycin.Approved, Investigational
GanciclovirThe metabolism of Ganciclovir can be decreased when combined with Solithromycin.Approved, Investigational
GitoformateThe serum concentration of Gitoformate can be increased when it is combined with Solithromycin.Experimental
Lanatoside CThe serum concentration of Lanatoside C can be increased when it is combined with Solithromycin.Experimental
MethylergometrineThe serum concentration of Methylergometrine can be increased when it is combined with Solithromycin.Approved
MetildigoxinThe serum concentration of Metildigoxin can be increased when it is combined with Solithromycin.Experimental
MidazolamThe serum concentration of Midazolam can be increased when it is combined with Solithromycin.Approved, Illicit
OleandrinThe serum concentration of Oleandrin can be increased when it is combined with Solithromycin.Experimental, Investigational
OuabainThe serum concentration of Ouabain can be increased when it is combined with Solithromycin.Approved
PeruvosideThe serum concentration of Peruvoside can be increased when it is combined with Solithromycin.Experimental
PhenindioneThe serum concentration of Phenindione can be increased when it is combined with Solithromycin.Approved, Investigational
PhenprocoumonThe serum concentration of Phenprocoumon can be increased when it is combined with Solithromycin.Approved, Investigational
ProscillaridinThe serum concentration of Proscillaridin can be increased when it is combined with Solithromycin.Experimental
QuinineThe serum concentration of Quinine can be increased when it is combined with Solithromycin.Approved
RepaglinideThe serum concentration of Repaglinide can be increased when it is combined with Solithromycin.Approved, Investigational
RifabutinThe metabolism of Rifabutin can be decreased when combined with Solithromycin.Approved, Investigational
RifampicinThe metabolism of Rifampicin can be decreased when combined with Solithromycin.Approved
RifaximinThe metabolism of Rifaximin can be decreased when combined with Solithromycin.Approved, Investigational
SirolimusThe metabolism of Sirolimus can be decreased when combined with Solithromycin.Approved, Investigational
TacrolimusThe serum concentration of Tacrolimus can be increased when it is combined with Solithromycin.Approved, Investigational
TemsirolimusThe risk or severity of adverse effects can be increased when Solithromycin is combined with Temsirolimus.Approved
TerfenadineThe serum concentration of Terfenadine can be increased when it is combined with Solithromycin.Approved, Withdrawn
TheophyllineThe metabolism of Theophylline can be decreased when combined with Solithromycin.Approved
TioclomarolThe serum concentration of Tioclomarol can be increased when it is combined with Solithromycin.Experimental
TriazolamThe serum concentration of Triazolam can be increased when it is combined with Solithromycin.Approved, Investigational
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Solithromycin.Approved
VinblastineThe serum concentration of Vinblastine can be increased when it is combined with Solithromycin.Approved
VincamineThe serum concentration of Vincamine can be increased when it is combined with Solithromycin.Experimental
VincristineThe serum concentration of Vincristine can be increased when it is combined with Solithromycin.Approved, Investigational
VindesineThe serum concentration of Vindesine can be increased when it is combined with Solithromycin.Approved, Investigational
VinflunineThe serum concentration of Vinflunine can be increased when it is combined with Solithromycin.Approved, Investigational
VinorelbineThe serum concentration of Vinorelbine can be increased when it is combined with Solithromycin.Approved, Investigational
WarfarinThe serum concentration of Warfarin can be increased when it is combined with Solithromycin.Approved
Food Interactions
Not Available

References

General References
  1. Reinert RR: Clinical efficacy of ketolides in the treatment of respiratory tract infections. J Antimicrob Chemother. 2004 Jun;53(6):918-27. Epub 2004 Apr 29. [PubMed:15117934]
  2. Menache D: Replacement therapy in patients with hereditary antithrombin III deficiency. Semin Hematol. 1991 Jan;28(1):31-8. [PubMed:2017690]
  3. Farrell DJ, Sader HS, Castanheira M, Biedenbach DJ, Rhomberg PR, Jones RN: Antimicrobial characterisation of CEM-101 activity against respiratory tract pathogens, including multidrug-resistant pneumococcal serogroup 19A isolates. Int J Antimicrob Agents. 2010 Jun;35(6):537-43. doi: 10.1016/j.ijantimicag.2010.01.026. Epub 2010 Mar 7. [PubMed:20211548]
  4. McGhee P, Clark C, Kosowska-Shick KM, Nagai K, Dewasse B, Beachel L, Appelbaum PC: In vitro activity of CEM-101 against Streptococcus pneumoniae and Streptococcus pyogenes with defined macrolide resistance mechanisms. Antimicrob Agents Chemother. 2010 Jan;54(1):230-8. doi: 10.1128/AAC.01123-09. Epub 2009 Nov 2. [PubMed:19884376]
  5. Putnam SD, Castanheira M, Moet GJ, Farrell DJ, Jones RN: CEM-101, a novel fluoroketolide: antimicrobial activity against a diverse collection of Gram-positive and Gram-negative bacteria. Diagn Microbiol Infect Dis. 2010 Apr;66(4):393-401. doi: 10.1016/j.diagmicrobio.2009.10.013. [PubMed:20022192]
  6. Putnam SD, Sader HS, Farrell DJ, Biedenbach DJ, Castanheira M: Antimicrobial characterisation of solithromycin (CEM-101), a novel fluoroketolide: activity against staphylococci and enterococci. Int J Antimicrob Agents. 2011 Jan;37(1):39-45. doi: 10.1016/j.ijantimicag.2010.08.021. [PubMed:21075602]
  7. Llano-Sotelo B, Dunkle J, Klepacki D, Zhang W, Fernandes P, Cate JH, Mankin AS: Binding and action of CEM-101, a new fluoroketolide antibiotic that inhibits protein synthesis. Antimicrob Agents Chemother. 2010 Dec;54(12):4961-70. doi: 10.1128/AAC.00860-10. Epub 2010 Sep 20. [PubMed:20855725]
External Links
PubChem Compound
25242512
PubChem Substance
310265196
ChemSpider
25056854
ChEMBL
CHEMBL1232510
HET
EM1
Wikipedia
Solithromycin
PDB Entries
4www

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentBacterial Infections2
1CompletedTreatmentGonorrhoea1
2CompletedTreatmentCommunity-Acquired Bacterial Pneumonia (CABP)1
2CompletedTreatmentNonalcoholic Steatohepatitis1
2CompletedTreatmentUncomplicated Urogenital Gonorrhea1
2TerminatedTreatmentPulmonary Disease, Chronic Obstructive1
2, 3RecruitingTreatmentCommunity-Acquired Bacterial Pneumonia (CABP)1
3CompletedTreatmentCommunity-Acquired Bacterial Pneumonia (CABP)2
3CompletedTreatmentUncomplicated Urogenital Gonorrhea1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0167 mg/mLALOGPS
logP4.22ALOGPS
logP5.76ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)12.8ChemAxon
pKa (Strongest Basic)7.68ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area197.87 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity230.73 m3·mol-1ChemAxon
Polarizability90.81 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as aminoglycosides. These are molecules or a portion of a molecule composed of amino-modified sugars.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Aminoglycosides
Alternative Parents
Phenyl-1,2,3-triazoles / Aniline and substituted anilines / Oxazolidinones / Oxanes / Alpha-haloketones / Carbamate esters / Heteroaromatic compounds / 1,2-aminoalcohols / Trialkylamines / Secondary alcohols
show 15 more
Substituents
Aminoglycoside core / Phenyltriazole / Phenyl-1,2,3-triazole / Aniline or substituted anilines / Monocyclic benzene moiety / Oxane / Oxazolidinone / Benzenoid / Heteroaromatic compound / Alpha-haloketone
show 37 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Kuper JI, D'Aprile M: Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease. Clin Pharmacokinet. 2000 Sep;39(3):203-14. [PubMed:11020135]

Drug created on November 12, 2015 09:46 / Updated on August 02, 2018 06:17