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
DrugInteraction
(R)-warfarinThe serum concentration of (R)-warfarin can be increased when it is combined with Solithromycin.
(S)-WarfarinThe serum concentration of (S)-Warfarin can be increased when it is combined with Solithromycin.
3-isobutyl-1-methyl-7H-xanthineThe metabolism of 3-isobutyl-1-methyl-7H-xanthine can be decreased when combined with Solithromycin.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Solithromycin.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Solithromycin.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Solithromycin.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Solithromycin.
7-DeazaguanineThe metabolism of 7-Deazaguanine can be decreased when combined with Solithromycin.
7,9-DimethylguanineThe metabolism of 7,9-Dimethylguanine can be decreased when combined with Solithromycin.
8-azaguanineThe metabolism of 8-azaguanine can be decreased when combined with Solithromycin.
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 November 02, 2018 07:01