WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H314272
CAS#: 760981-83-7
Description: Solithromycin, also known as CEM-101 and OP-1068, is a 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 pathogens, including macrolide-resistant strains. Solithromycin has activity against a wide variety of pathogens, and further research is being conducted for other infections.
Hodoodo Cat#: H314272
Name: Solithromycin
CAS#: 760981-83-7
Chemical Formula: C43H65FN6O10
Exact Mass: 844.47
Molecular Weight: 845.010
Elemental Analysis: C, 61.12; H, 7.75; F, 2.25; N, 9.95; O, 18.93
Synonym: CEM101; CEM101; CEM 101; OP1068; OP1068; OP 1068; Solithromycin
IUPAC/Chemical Name: (3aS,4R,7R,9R,10R,11R,13R,15S,15aR)-1-(4-(4-(3-aminophenyl)-1H-1,2,3-triazol-1-yl)butyl)-10-(((2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-4-ethyl-7-fluoro-11-methoxy-3a,7,9,11,13,15-hexamethyloctahydro-1H-[1]oxacyclotetradecino[4,3-d]oxazole-2,6,8,14(7H,9H)-tetraone
InChi Key: IXXFZUPTQVDPPK-QIFQIIIXSA-N
InChi Code: 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
SMILES Code: CC[C@@H]1[C@]2(C)[C@H](N(CCCCN3C=C(C4=CC(N)=CC=C4)N=N3)C(O2)=O)[C@H](C)C([C@H](C)C[C@@](C)(OC)[C@H](O[C@H]5[C@H](O)[C@@H](N(C)C)C[C@@H](C)O5)[C@@H](C)C([C@@](C)(F)C(O1)=O)=O)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO.
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Solithromycin (CEM-101) is an antimicrobial agent that binds to the large 50S subunit of the ribosome, with IC50s of 7.5 ng/mL, 40 ng/mL, and 125 ng/mL for Streptococcus pneumonia, Staphylococcus aureus, and Haemophilus influenzae, respectively. |
| In vitro activity: | The MIC50 and the MIC90 of solithromycin were ≤0.008 and 0.015 µg/ml against erythromycin-susceptible strains, which were respectfully at least 4-fold and 3-fold lower than that of penicillin, the first-line agent both for intrapartum antibiotic prophylaxis and for the treatment of GBS infections in adults. Against erythromycin-resistant strains, solithromycin had a MIC50 of 0.03 µg/ml and a MIC90 of 0.125 µg/ml. The MIC50 of penicillin was 0.032 and comparable to that of solithromycin, whereas the MIC90 of penicillin was 2.7-fold lower than that of solithromycin against erythromycin-resistant strains. Reference: Antimicrob Agents Chemother. 2014 Mar; 58(3): 1693–1698. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957870/ |
| In vivo activity: | Pilot studies in animals infected with NTHi 1086 (MIC/MBC, 8/16 μg/ml [believed to be above the susceptible breakpoint]) administered at 25, 50, or 150 mg/kg per orogastric tube were performed to obtain plasma and middle ear fluid samples for determination of the appropriate dose for future studies. Solithromycin administered at 150 mg/kg/dose daily for 3 days was used in all subsequent studies except where a different dose is specified. The concentration-time curves of solithromycin in plasma and MEF are illustrated in Fig. 1. Solithromycin (at 150 mg/kg/day for 3 days) demonstrated peak plasma and extracellular MEF concentrations of 2.2 and 1.7 μg/ml at 2 and 8 h, respectively, after administration of the first dose. By day 3, the Cmax values increased to 4.5 μg/ml in plasma and 4.28 μg/ml in extracellular MEF at 4 and 8 h, respectively. The 24-h plasma AUC0–24 values were 27.4 and 54 μg · h/ml after dose 1 and dose 3, respectively. The 24-h extracellular MEF AUC0–24 values were 28.2 and 98.6 μg · h/ml after dose 1 and dose 3, respectively. Reference: Antimicrob Agents Chemother. 2016 Sep; 60(9): 5533–5538. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997842/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 44.8 | 53.06 | |
| DMF | 5.0 | 5.92 | |
| Ethanol | 25.0 | 29.59 |
The following data is based on the product molecular weight 845.01 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Yao W, Xu G, Li D, Bai B, Wang H, Cheng H, Zheng J, Sun X, Lin Z, Deng Q, Yu Z. Staphylococcus aureus with an erm-mediated constitutive macrolide-lincosamide-streptogramin B resistance phenotype has reduced susceptibility to the new ketolide, solithromycin. BMC Infect Dis. 2019 Feb 19;19(1):175. doi: 10.1186/s12879-019-3779-8. PMID: 30782125; PMCID: PMC6381629. 2. Piccinelli G, Fernandes P, Bonfanti C, Caccuri F, Caruso A, De Francesco MA. In vitro activity of solithromycin against erythromycin-resistant Streptococcus agalactiae. Antimicrob Agents Chemother. 2014;58(3):1693-8. doi: 10.1128/AAC.02210-13. Epub 2013 Dec 30. Erratum in: Antimicrob Agents Chemother. 2018 Oct 24;62(11): PMID: 24379197; PMCID: PMC3957870. 3. Okusanya OO, Forrest A, Bhavnani SM, Fernandes P, Ambrose PG, Andes DR. Pharmacokinetic/Pharmacodynamic Evaluation of Solithromycin against Streptococcus pneumoniae Using Data from a Neutropenic Murine Lung Infection Model. Antimicrob Agents Chemother. 2019 Jul 25;63(8):e02606-18. doi: 10.1128/AAC.02606-18. PMID: 31182534; PMCID: PMC6658793. 4. Figueira M, Fernandes P, Pelton SI. Efficacy of Solithromycin (CEM-101) for Experimental Otitis Media Caused by Nontypeable Haemophilus influenzae and Streptococcus pneumoniae. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5533-8. doi: 10.1128/AAC.00863-16. PMID: 27401563; PMCID: PMC4997842. |
| In vitro protocol: | 1. Yao W, Xu G, Li D, Bai B, Wang H, Cheng H, Zheng J, Sun X, Lin Z, Deng Q, Yu Z. Staphylococcus aureus with an erm-mediated constitutive macrolide-lincosamide-streptogramin B resistance phenotype has reduced susceptibility to the new ketolide, solithromycin. BMC Infect Dis. 2019 Feb 19;19(1):175. doi: 10.1186/s12879-019-3779-8. PMID: 30782125; PMCID: PMC6381629. 2. Piccinelli G, Fernandes P, Bonfanti C, Caccuri F, Caruso A, De Francesco MA. In vitro activity of solithromycin against erythromycin-resistant Streptococcus agalactiae. Antimicrob Agents Chemother. 2014;58(3):1693-8. doi: 10.1128/AAC.02210-13. Epub 2013 Dec 30. Erratum in: Antimicrob Agents Chemother. 2018 Oct 24;62(11): PMID: 24379197; PMCID: PMC3957870. |
| In vivo protocol: | 1. Okusanya OO, Forrest A, Bhavnani SM, Fernandes P, Ambrose PG, Andes DR. Pharmacokinetic/Pharmacodynamic Evaluation of Solithromycin against Streptococcus pneumoniae Using Data from a Neutropenic Murine Lung Infection Model. Antimicrob Agents Chemother. 2019 Jul 25;63(8):e02606-18. doi: 10.1128/AAC.02606-18. PMID: 31182534; PMCID: PMC6658793. 2. Figueira M, Fernandes P, Pelton SI. Efficacy of Solithromycin (CEM-101) for Experimental Otitis Media Caused by Nontypeable Haemophilus influenzae and Streptococcus pneumoniae. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5533-8. doi: 10.1128/AAC.00863-16. PMID: 27401563; PMCID: PMC4997842. |
1: Jamieson BD, Ciric S, Fernandes P. Safety and Pharmacokinetics of Solithromycin in Subjects with Hepatic Impairment. Antimicrob Agents Chemother. 2015 Apr 13. pii: AAC.04652-14. [Epub ahead of print] PubMed PMID: 25870056.
2: Vandevelde NM, Tulkens PM, Muccioli GG, Van Bambeke F. Modulation of the activity of moxifloxacin and solithromycin in an in vitro pharmacodynamic model of Streptococcus pneumoniae naive and induced biofilms. J Antimicrob Chemother. 2015 Feb 23. pii: dkv032. [Epub ahead of print] PubMed PMID: 25712316.
3: Farrell DJ, Mendes RE, Jones RN. Antimicrobial Activity of Solithromycin against Serotyped Macrolide-Resistant Streptococcus pneumoniae Isolates Collected from U.S. Medical Centers in 2012. Antimicrob Agents Chemother. 2015 Apr;59(4):2432-4. doi: 10.1128/AAC.04568-14. Epub 2015 Jan 20. PubMed PMID: 25605359; PubMed Central PMCID: PMC4356815.
4: Keelan JA, Pugazhenthi K. Trans-placental passage and anti-inflammatory effects of solithromycin in the human placenta. Placenta. 2014 Dec;35(12):1043-8. doi: 10.1016/j.placenta.2014.09.009. Epub 2014 Sep 22. PubMed PMID: 25280973.
5: Miura Y, Payne MS, Keelan JA, Noe A, Carter S, Watts R, Spiller OB, Jobe AH, Kallapur SG, Saito M, Stock SJ, Newnham JP, Kemp MW. Maternal intravenous treatment with either azithromycin or solithromycin clears Ureaplasma parvum from the amniotic fluid in an ovine model of intrauterine infection. Antimicrob Agents Chemother. 2014 Sep;58(9):5413-20. doi: 10.1128/AAC.03187-14. Epub 2014 Jun 30. PubMed PMID: 24982089; PubMed Central PMCID: PMC4135857.
6: Jensen JS, Fernandes P, Unemo M. In vitro activity of the new fluoroketolide solithromycin (CEM-101) against macrolide-resistant and -susceptible Mycoplasma genitalium strains. Antimicrob Agents Chemother. 2014 Jun;58(6):3151-6. doi: 10.1128/AAC.02411-14. Epub 2014 Mar 17. PubMed PMID: 24637681; PubMed Central PMCID: PMC4068426.
7: Piccinelli G, Fernandes P, Bonfanti C, Caccuri F, Caruso A, De Francesco MA. In vitro activity of solithromycin against erythromycin-resistant Streptococcus agalactiae. Antimicrob Agents Chemother. 2014;58(3):1693-8. doi: 10.1128/AAC.02210-13. Epub 2013 Dec 30. PubMed PMID: 24379197; PubMed Central PMCID: PMC3957870.
8: Mallegol J, Fernandes P, Melano RG, Guyard C. Antimicrobial activity of solithromycin against clinical isolates of Legionella pneumophila serogroup 1. Antimicrob Agents Chemother. 2014;58(2):909-15. doi: 10.1128/AAC.01639-13. Epub 2013 Nov 25. PubMed PMID: 24277019; PubMed Central PMCID: PMC3910839.
9: Keelan JA, Kemp MW, Payne MS, Johnson D, Stock SJ, Saito M, Fernandes P, Newnham JP. Maternal administration of solithromycin, a new, potent, broad-spectrum fluoroketolide antibiotic, achieves fetal and intra-amniotic antimicrobial protection in a pregnant sheep model. Antimicrob Agents Chemother. 2014;58(1):447-54. doi: 10.1128/AAC.01743-13. Epub 2013 Nov 4. PubMed PMID: 24189250; PubMed Central PMCID: PMC3910757.
10: Mallegol J, Fernandes P, Seah C, Guyard C, Melano RG. Determination of in vitro activity of solithromycin at different pHs and its intracellular activity tested against clinical isolates of Neisseria gonorrhoeae from a laboratory collection. Antimicrob Agents Chemother. 2013 Jun 24. [Epub ahead of print] PubMed PMID: 23796936; PubMed Central PMCID: PMC3754335.
11: Kobayashi Y, Wada H, Rossios C, Takagi D, Charron C, Barnes PJ, Ito K. A novel macrolide/fluoroketolide, solithromycin (CEM-101), reverses corticosteroid insensitivity via phosphoinositide 3-kinase pathway inhibition. Br J Pharmacol. 2013 Jul;169(5):1024-34. doi: 10.1111/bph.12187. PubMed PMID: 23758162; PubMed Central PMCID: PMC3696326.
12: Oldach D, Clark K, Schranz J, Das A, Craft JC, Scott D, Jamieson BD, Fernandes P. Randomized, double-blind, multicenter phase 2 study comparing the efficacy and safety of oral solithromycin (CEM-101) to those of oral levofloxacin in the treatment of patients with community-acquired bacterial pneumonia. Antimicrob Agents Chemother. 2013 Jun;57(6):2526-34. doi: 10.1128/AAC.00197-13. Epub 2013 Mar 18. PubMed PMID: 23507282; PubMed Central PMCID: PMC3716175.
13: Kobayashi Y, Wada H, Rossios C, Takagi D, Higaki M, Mikura S, Goto H, Barnes PJ, Ito K. A novel macrolide solithromycin exerts superior anti-inflammatory effect via NF-κB inhibition. J Pharmacol Exp Ther. 2013 Apr;345(1):76-84. doi: 10.1124/jpet.112.200733. Epub 2013 Jan 28. PubMed PMID: 23359665.
14: Rodgers W, Frazier AD, Champney WS. Solithromycin inhibition of protein synthesis and ribosome biogenesis in Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. Antimicrob Agents Chemother. 2013 Apr;57(4):1632-7. doi: 10.1128/AAC.02316-12. Epub 2013 Jan 14. PubMed PMID: 23318809; PubMed Central PMCID: PMC3623315.
15: Rodvold KA, Gotfried MH, Still JG, Clark K, Fernandes P. Comparison of plasma, epithelial lining fluid, and alveolar macrophage concentrations of solithromycin (CEM-101) in healthy adult subjects. Antimicrob Agents Chemother. 2012 Oct;56(10):5076-81. doi: 10.1128/AAC.00766-12. Epub 2012 Jul 16. PubMed PMID: 22802254; PubMed Central PMCID: PMC3457395.
16: Golparian D, Fernandes P, Ohnishi M, Jensen JS, Unemo M. In vitro activity of the new fluoroketolide solithromycin (CEM-101) against a large collection of clinical Neisseria gonorrhoeae isolates and international reference strains, including those with high-level antimicrobial resistance: potential treatment option for gonorrhea? Antimicrob Agents Chemother. 2012 May;56(5):2739-42. doi: 10.1128/AAC.00036-12. Epub 2012 Feb 21. PubMed PMID: 22354296; PubMed Central PMCID: PMC3346660.
17: Wittlin S, Ekland E, Craft JC, Lotharius J, Bathurst I, Fidock DA, Fernandes P. In vitro and in vivo activity of solithromycin (CEM-101) against Plasmodium species. Antimicrob Agents Chemother. 2012 Feb;56(2):703-7. doi: 10.1128/AAC.05039-11. Epub 2011 Nov 14. PubMed PMID: 22083475; PubMed Central PMCID: PMC3264280.
18: Still JG, Schranz J, Degenhardt TP, Scott D, Fernandes P, Gutierrez MJ, Clark K. Pharmacokinetics of solithromycin (CEM-101) after single or multiple oral doses and effects of food on single-dose bioavailability in healthy adult subjects. Antimicrob Agents Chemother. 2011 May;55(5):1997-2003. doi: 10.1128/AAC.01429-10. Epub 2011 Jan 31. PubMed PMID: 21282444; PubMed Central PMCID: PMC3088205.
19: 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 PMID: 21075602.
20: Farrell DJ, Castanheira M, Sader HS, Jones RN. The in vitro evaluation of solithromycin (CEM-101) against pathogens isolated in the United States and Europe (2009). J Infect. 2010 Dec;61(6):476-83. doi: 10.1016/j.jinf.2010.08.010. Epub 2010 Sep 8. PubMed PMID: 20831882.
