Tetracycline; protein synthesis of bacteria; Bacterial 30S ribosomal subunit (binds to the A site of the 30S subunit, inhibiting protein synthesis) [1][2][3]
Omadacycline is a novel, aminomethyl tetracycline antibiotic being developed for oral and intravenous (IV) administration to treat community-acquired bacterial infections such as acute bacterial skin and skin structure infections (ABSSSI), community-acquired bacterial pneumonia (CABP), and urinary tract infections (UTI). In vitro, omadacycline has activity against Gram-positive and Gram-negative aerobes, anaerobes, and atypical pathogens including Legionella and Chlamydia spp. Omadacycline offers once daily oral and IV dosing and a clinical tolerability and safety profile that compares favorably with contemporary antibiotics used across serious community-acquired infections where resistance has rendered many less effective. In studies in patients with complicated skin and skin structure infections, including those with MRSA infections, omadacycline exhibited an efficacy and tolerability profile that was comparable to linezolid. Ongoing and planned clinical studies are evaluating omadacycline as monotherapy for treating serious community-acquired bacterial infections including Acute Bacterial Skin and Skin Structure Infections (ABSSSI) and Community-Acquired Bacterial Pneumonia (CABP). This review provides an overview of the discovery, microbiology, nonclinical data, and available clinical safety and efficacy data for omadacycline, with reference to other contemporary tetracycline-derived antibiotics.

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- Antibacterial spectrum and activity: Omadacycline exhibited potent activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentrations (MIC90) of 0.25-1 μg/mL, Streptococcus pneumoniae (MIC90 0.06-0.25 μg/mL), and vancomycin-resistant Enterococcus (VRE, MIC90 0.5-2 μg/mL). It also showed activity against some Gram-negative bacteria such as Haemophilus influenzae (MIC90 2 μg/mL) and Moraxella catarrhalis (MIC90 0.25 μg/mL). The drug retained activity against tetracycline-resistant strains due to resistance to efflux pumps and ribosomal protection proteins [2][3]
- Time-kill kinetics: Against S. aureus (including MRSA) and S. pneumoniae, Omadacycline displayed concentration-dependent bactericidal activity at 2-4 times the MIC, achieving ≥3 log10 CFU/mL reduction in bacterial counts within 24 hours [2]
- Post-antibiotic effect (PAE): For S. aureus and S. pneumoniae, Omadacycline exhibited a PAE of 1.5-3 hours at 2-4 times the MIC [2]

Omadacycline is a novel, aminomethyl tetracycline antibiotic being developed for oral and intravenous (IV) administration to treat community-acquired bacterial infections such as acute bacterial skin and skin structure infections (ABSSSI), community-acquired bacterial pneumonia (CABP), and urinary tract infections (UTI). In vitro, omadacycline has activity against Gram-positive and Gram-negative aerobes, anaerobes, and atypical pathogens including Legionella and Chlamydia spp. Omadacycline offers once daily oral and IV dosing and a clinical tolerability and safety profile that compares favorably with contemporary antibiotics used across serious community-acquired infections where resistance has rendered many less effective. In studies in patients with complicated skin and skin structure infections, including those with MRSA infections, omadacycline exhibited an efficacy and tolerability profile that was comparable to linezolid. Ongoing and planned clinical studies are evaluating omadacycline as monotherapy for treating serious community-acquired bacterial infections including Acute Bacterial Skin and Skin Structure Infections (ABSSSI) and Community-Acquired Bacterial Pneumonia (CABP). This review provides an overview of the discovery, microbiology, nonclinical data, and available clinical safety and efficacy data for omadacycline, with reference to other contemporary tetracycline-derived antibiotics.

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- Antibacterial spectrum and activity: Omadacycline exhibited potent activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentrations (MIC90) of 0.25-1 μg/mL, Streptococcus pneumoniae (MIC90 0.06-0.25 μg/mL), and vancomycin-resistant Enterococcus (VRE, MIC90 0.5-2 μg/mL). It also showed activity against some Gram-negative bacteria such as Haemophilus influenzae (MIC90 2 μg/mL) and Moraxella catarrhalis (MIC90 0.25 μg/mL). The drug retained activity against tetracycline-resistant strains due to resistance to efflux pumps and ribosomal protection proteins [2][3]
- Time-kill kinetics: Against S. aureus (including MRSA) and S. pneumoniae, Omadacycline displayed concentration-dependent bactericidal activity at 2-4 times the MIC, achieving ≥3 log10 CFU/mL reduction in bacterial counts within 24 hours [2]
- Post-antibiotic effect (PAE): For S. aureus and S. pneumoniae, Omadacycline exhibited a PAE of 1.5-3 hours at 2-4 times the MIC [2]

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Omadacycline demonstrates potent in vitro antibacterial activity against a broad spectrum of bacteria. It is active against Gram-positive bacteria including Staphylococcus aureus (MIC range 0.125–1 µg/mL for tet(M)-containing strains and 0.125–0.25 µg/mL for tet(K)-containing strains), methicillin-resistant S. aureus (MRSA), penicillin-resistant and multidrug-resistant Streptococcus pneumoniae (MIC ≤0.06 µg/mL for many resistant strains), vancomycin-resistant Enterococcus faecalis and E. faecium (MIC 0.25 µg/mL for strains with both tet(M) and tet(L) resistance genes), and β-hemolytic streptococci. [1]
It is also active against Gram-negative bacteria such as Haemophilus influenzae (MIC50 1 µg/mL), Klebsiella pneumoniae (MIC50 2 µg/mL), Escherichia coli (MIC50 1 µg/mL, MIC 2 µg/mL for tet(A)-expressing strains), Moraxella catarrhalis (MIC90 0.25 µg/mL), and others including Legionella pneumophila (MIC range 0.06–1 µg/mL) and Chlamydia pneumoniae (MIC range 0.03–0.5 µg/mL, MIC50 0.06 µg/mL). [1]
Activity is shown against anaerobic bacteria: Clostridium difficile (MIC range 0.25–8 µg/mL, MIC50 0.25 µg/mL), Peptostreptococcus spp. (MIC range 0.06–2 µg/mL, MIC50 0.12 µg/mL), and various Bacteroides and Precotella species. [1]
It is active against atypical pathogens Mycoplasma hominis (MIC50 0.032 µg/mL, MIC90 0.063 µg/mL), Mycoplasma pneumoniae (MIC90 0.25 µg/mL), and Ureaplasma spp. (MIC50 1 µg/mL, MIC90 2 µg/mL). Activity is retained against macrolide- and tetracycline-resistant strains. [1]
It shows promising activity against rapidly growing mycobacteria: Mycobacterium abscessus (MIC50 1 µg/mL, MIC90 2 µg/mL), M. chelonae (MIC50 0.125 µg/mL, MIC90 0.25 µg/mL), and M. fortuitum (MIC50 0.125 µg/mL, MIC90 0.5 µg/mL). [1]

In vivo efficacy of omadacycline is demonstrated using an intraperitoneal infection model in mice. A single intravenous dose of omadacycline exhibits efficacy against Streptococcus pneumoniae, Escherichia coli, and Staphylococcus aureus, including tet (M) and tet (K) efflux-containing strains and MRSA strains. The 50% effective doses (ED50s) for Streptococcus pneumoniae obtained ranged from 0.45 mg/kg to 3.39 mg/kg, the ED50s for Staphylococcus aureus obtained ranges from 0.30 mg/kg to 1.74 mg/kg, and the ED50 for Escherichia coli is 2.02 mg/kg.

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- Efficacy in murine infection models: In a murine thigh infection model with S. aureus (including MRSA) and S. pneumoniae, Omadacycline administered subcutaneously (10-80 mg/kg) dose-dependently reduced bacterial counts (≥3 log10 CFU reduction at higher doses). In a murine pneumonia model with S. pneumoniae, intravenous administration (20-60 mg/kg) significantly reduced lung bacterial burden and improved survival rates [2]
- Efficacy in clinical trials: In phase 3 trials for acute bacterial skin and skin structure infections (ABSSSI), Omadacycline (intravenous followed by oral) showed non-inferiority to linezolid, with clinical success rates of 87.5% vs. 85.1% (p=0.44). For community-acquired bacterial pneumonia (CABP), it was non-inferior to moxifloxacin, with clinical success rates of 81.1% vs. 82.7% (p=0.66) [1][3][4]

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In Phase II clinical trials for acute bacterial skin and skin structure infections (ABSSSI), Omadacycline (100 mg IV once daily, with option to switch to 300 mg oral once daily) demonstrated comparable efficacy and safety to linezolid (600 mg IV/oral twice daily), meeting non-inferiority criteria. Clinical success rates were high, including against MRSA. [1]
In Phase III trials for ABSSSI (OASIS-1 and OASIS-2), Omadacycline (IV/oral regimen) was non-inferior to linezolid, with similar safety and side-effect profiles, and showed high clinical success rates across pathogens including MRSA and E. faecalis. [1]
In Phase III trials for community-acquired bacterial pneumonia (CABP), Omadacycline (100 mg IV twice daily for two doses, then 100 mg IV once daily, with option to switch to oral) was non-inferior to moxifloxacin (400 mg IV/oral once daily), showing similar efficacy against atypical pathogens, Gram-negative bacteria, and S. pneumoniae. [1]

In vitro stability and drug–drug interaction potential of omadacycline[5]
The stability of omadacycline (4.8 and 48 μM) was assessed in human microsomes and hepatocytes. After 30 min incubation of omadacycline in human microsomes, >90% of omadacycline was recovered intact. Similarly, after incubation of omadacycline up to 24 h in human hepatocytes, >86% was recovered intact. These results indicate that omadacycline is not metabolized to any significant extent. The potential for drug-drug-interactions with omadacycline was assessed using either pooled human liver microsome preparations, S9, liver cytosol, or recombinant flavin monooxygenases (FMO1, FMO3, FMO5). Induction of CYP450 isozymes was evaluated in primary human hepatocytes incubated with omadacycline 1–100 μM and a substrate probe for 24 and 48 h. Inhibition of CYP450 isozymes was evaluated with pooled human microsomes at omadacycline concentrations of 1–50 μM and isozyme specific substrates at concentrations approximating the Km of each substrate. Isozymes evaluated included CYP 1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2J2, and 3A4/5. Omadacycline did not induce CYP isozymes, and no or minimal (<40% of maximal positive control response) induction of their mRNAs was observed. Omadacycline demonstrated no significant inhibition of CYP isozyme activity. In addition, there was no time-dependent inhibition of omadacycline or its possible metabolites for CYP1A2 2C9, 2D6 or 3A4/5.[5]

The omadacycline MIC90s for MRSA, VRE, and beta-hemolytic streptococci are 1.0 μg/mL, 0.25 μg/mL, and 0.5 μg/mL, respectively, and the omadacycline MIC90s for PRSP and H. influenzae are 0.25 μg/ml and 2.0 μg/mL, respectively. Omadacycline is active against organisms demonstrating the two major mechanisms of resistance, ribosomal protection and active tetracycline efflux[1]. Omadacycline inhibits protein synthesis while having no significant effect on RNA, DNA and peptidoglycan synthesis. Further, omadacycline binds to the tetracycline binding site on the 30S subunit of the bacterial ribosome with enhanced binding similar to tigecycline based on additional molecular interactions.

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- MIC determination: Broth microdilution assays were performed according to CLSI guidelines. Bacterial strains were inoculated into cation-adjusted Mueller-Hinton broth containing serial dilutions of Omadacycline (0.015-128 μg/mL) and incubated at 35°C for 18-24 hours. The MIC was defined as the lowest concentration inhibiting visible growth [2]
- Time-kill assay: Bacterial cultures (10^6 CFU/mL) were exposed to Omadacycline at concentrations of 0.5×, 1×, 2×, and 4× MIC. Aliquots were taken at 0, 4, 8, 12, and 24 hours, plated on agar, and colony-forming units (CFU) were counted after incubation [2]

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The primary cell-based assays described are standard broth microdilution methods to determine Minimum Inhibitory Concentrations (MICs) against various bacterial strains. The detailed protocol involves preparing serial dilutions of Omadacycline in appropriate media, inoculating with standardized bacterial suspensions, incubating under specified conditions, and visually assessing growth inhibition to determine the MIC. Comparative studies were performed against other antibiotics (tetracyclines, cephalosporins, aminoglycosides, quinolones, etc.) on panels of clinically significant bacteria, including those carrying specific resistance genes (e.g., tet(M), tet(K), tet(L)). [1]

0.45 mg/kg to 3.39 mg/kg; i.p. Mice\nSystemic i.p. challenge model. Six-week-old, specific-pathogen-free, male CD-1 mice, weighing 18 to 30 g were used for all experiments. At 1 h postinfection (p.i.), mice were dosed intravenously (i.v.) with omadacycline or comparator compounds of interest, dissolved in sterile saline for injection at a volume of 10 ml/kg. All drug doses were formulated fresh immediately prior to administration and adjusted to account for percent activity. A minimum of four dose levels were tested per experiment with 5 mice/group. The typical doses tested ranged from 0.11 to 18 mg/kg of body weight, with exceptions for comparators that required significantly higher or lower doses to achieve 50% efficacy (dose range minimum-maximum, 0.08 to 54 mg/kg). Each study also included an untreated control group. Mice were housed in filter-topped cages in an isolated room and monitored for morbidity at least every 24 h for 7 days. Efficacy was determined by calculating the 50% effective dose (ED50) for all drugs tested. The ED50 is defined as the dose required to achieve 50% survival at 7 days p.i. and was estimated when possible using the formula y = 1/[1 + 10(log(k)-log(x)× 4.2)], where k = 0.5, by nonlinear regression analysis with Prism, version 3.0 software. [2]\nSystemic i.p. challenge model. Six-week-old, specific-pathogen-free, male CD-1 mice, weighing 18 to 30 g were used for all experiments. At 1 h postinfection (p.i.), mice were dosed intravenously (i.v.) with omadacycline or comparator compounds of interest, dissolved in sterile saline for injection at a volume of 10 ml/kg. All drug doses were formulated fresh immediately prior to administration and adjusted to account for percent activity. A minimum of four dose levels were tested per experiment with 5 mice/group. The typical doses tested ranged from 0.11 to 18 mg/kg of body weight, with exceptions for comparators that required significantly higher or lower doses to achieve 50% efficacy (dose range minimum-maximum, 0.08 to 54 mg/kg). Each study also included an untreated control group. Mice were housed in filter-topped cages in an isolated room and monitored for morbidity at least every 24 h for 7 days. Efficacy was determined by calculating the 50% effective dose (ED50) for all drugs tested. The ED50 is defined as the dose required to achieve 50% survival at 7 days p.i. and was estimated when possible using the formula y = 1/[1 + 10(log(k)-log(x)× 4.2)], where k = 0.5, by nonlinear regression analysis with Prism, version 3.0 software. [2]

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\n- Murine thigh infection model: Immunocompromised mice were inoculated intramuscularly with S. aureus or S. pneumoniae (10^6-10^7 CFU). Omadacycline was administered subcutaneously at 0, 4, and 8 hours post-inoculation (doses 10-80 mg/kg). Thighs were harvested 24 hours post-inoculation, homogenized, and bacterial counts were determined by plating [2]
\n - Murine pneumonia model: Mice were inoculated intranasally with S. pneumoniae (10^7 CFU). Omadacycline was administered intravenously at 6 and 24 hours post-inoculation (doses 20-60 mg/kg). Lungs were collected 48 hours post-inoculation for bacterial enumeration and histopathological analysis [2]

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\nThe literature mentions in vivo efficacy studies in murine models (e.g., murine neutropenic thigh infection model) but does not provide a detailed, step-by-step animal protocol including drug formulation, dosing regimen, route, and frequency for these preclinical studies. Clinical trial protocols in humans are described in more detail. [1]
\nFor clinical studies: In Phase I, various oral and intravenous doses were tested to assess pharmacokinetics and tolerability. In Phase II/III skin infection studies (OASIS), patients received Omadacycline 100 mg IV once daily or 200 mg oral once daily (after initial IV loading in some trials), compared to linezolid 600 mg twice daily. In Phase III pneumonia studies (OPTIC), patients received Omadacycline 100 mg IV twice daily for two doses, then 100 mg IV once daily, with an option to switch to oral therapy, compared to moxifloxacin 400 mg once daily. [1]

Omalia cycline's pharmacokinetic profile best conforms to a linear three-compartment model, with zero-order kinetics for intravenous infusion and first-order kinetics for oral administration, taking into account the transport compartment to explain delayed absorption. The volume of distribution (Vd) of omaalia cycline is 190–204 L, the terminal elimination half-life (t½) is 13.5–17.1 h, the total clearance (CLT) is 8.8–10.6 L/h, and the protein binding rate in healthy subjects is 21.3%. The estimated oral bioavailability of omaalia cycline is 34.5%. Following a single oral dose of 300 mg (bioequivalent to 100 mg intravenously) of omaalia cycline, the peak plasma concentration (Cmax) in fasting subjects is 0.5–0.6 mg/L, and the area under the plasma concentration-time curve (AUC0–∞) is 9.6–11.9 mg·h/L. The area under the free plasma concentration-time curve divided by the minimum inhibitory concentration (fAUC24h/MIC) has been identified as a pharmacodynamic parameter for predicting the antibacterial efficacy of omalicycline. Multiple animal models, including neutropenic mouse models of lung infection, thigh infection, and intraperitoneal infection, have demonstrated the in vivo antibacterial efficacy of omalicycline. A phase II clinical trial for complicated skin and soft tissue infections (cSSSI) and three phase III clinical trials for acute bacterial skin and soft tissue infections (ABSSSI) and community-acquired bacterial pneumonia (CABP) have confirmed the safety and efficacy of omalicycline. The phase III clinical trials OASIS-1 (ABSSSI), OASIS-2 (ABSSSI), and OPTIC (CABP) demonstrated that omalicycline is non-inferior to linezolid (OASIS-1, OASIS-2) and moxifloxacin (OPTIC) in the treatment of ABSSSI and CABP, respectively. Currently, omalicycline is approved by the FDA for the treatment of ABSSSI and CABP. Phase II clinical trials for patients with acute cystitis and acute pyelonephritis are ongoing. Mild, transient gastrointestinal reactions are the main adverse reactions of omalicycline. Based on clinical trial data to date, the adverse reaction profile of omalicycline is similar to that of the study control drugs linezolid and moxifloxacin. Unlike tigecycline and eracycline, omalicycline is available in oral formulations, allowing for a gradual transition from intravenous to oral preparations, which may help patients be discharged earlier, receive outpatient treatment, and save on healthcare costs. Omalicycline has potential role in antimicrobial management regimens for the treatment of infections caused by drug-resistant and multidrug-resistant Gram-positive bacteria (including methicillin-resistant Staphylococcus aureus (MRSA)) and Gram-negative pathogens. [https://pubmed.ncbi.nlm.nih.gov/31970713/]

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- Absorption: The oral bioavailability of omalicycline in humans is approximately 34%. Food has no significant effect on absorption, but antacids and iron supplements reduce absorption through chelation [1][3]
- Distribution: Large volume of distribution (160-230 L), extensive tissue penetration (e.g., skin blister fluid, lung tissue), and concentrations higher than plasma concentrations [3]
- Metabolism: Minimal metabolism; approximately 95% of the drug is excreted unchanged [3]
- Excretion: Primarily eliminated via renal (35-45%) and non-renal (55-65%) pathways, with a terminal half-life of approximately 16-18 hours [1][3]
A phase I study evaluated the pharmacokinetics and dosing regimen of omalicycline. Results showed good tolerability after both oral and intravenous administration. Specific pharmacokinetic parameters (e.g., half-life, oral bioavailability, AUC, Cmax, clearance) were not provided in the literature. [1] Comparative pharmacokinetic studies of omalicycline and tigecycline were conducted in plasma, epithelial lining fluid, and alveolar cells of healthy subjects. [1]

Plasma protein binding rate: approximately 70% [3] - Adverse reactions: Common adverse reactions include nausea (10-15%), vomiting (5-8%), and diarrhea (4-6%). No significant nephrotoxicity or hepatotoxicity was observed in clinical trials [1][3][4] - Cardiovascular safety: In vitro studies have shown that omalicycline has no significant inhibitory effect on human ether-a-go-go-related gene (hERG) channels (IC50 >300 μM). In vivo telemetry studies in dogs have shown no effect on the QT interval at therapeutic doses [5]

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Use during pregnancy and lactation
◉ Overview of use during lactation
There is currently no information on the use of omalicycline during lactation. It is unclear how much omalicycline is secreted into breast milk, but even under optimal conditions, the oral absorption rate is only about 35%, and because breast milk contains calcium, even less of the drug is likely secreted into breast milk. The manufacturer states that breastfeeding is not recommended during treatment or for 4 days after the last dose. If the infant is breastfeeding, the infant's gut microbiota should be monitored for any impact, such as diarrhea, candidiasis (e.g., thrush, diaper rash), or rare rectal bleeding (suggesting possible antibiotic-associated colitis). As a theoretical precaution, prolonged or repeated treatments during breastfeeding should be avoided.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on breastfeeding and breast milk
No published information found as of the revision date.

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Omacycline was generally well tolerated in clinical trials. In a Phase I study, intravenous doses exceeding 300 mg resulted in a reversible increase in alanine aminotransferase (ALT). Oral doses exceeding 400 mg caused mild nausea. [1]
In comparative studies with tigecycline, omalicycline had a lower incidence of side effects, such as headache, nausea, and vomiting. [1]
In a phase I study of female patients with cystitis, the incidence of gastrointestinal adverse reactions (vomiting, nausea) was higher than expected, but the symptoms were mild, transient, and did not lead to participants withdrawing from the trial. [1]

[1]. Pharmaceuticals (Basel). 2019 Apr 21;12(2):63.

[2]. Antimicrob Agents Chemother. 2014;58(2):1127-35.

[3]. Drugs. 2020 Feb;80(3):285-313.

[4]. Drugs. 2018 Dec;78(18):1931-1937.

[5]. Bioorg Med Chem.2016 Dec 15;24(24):6409-6419.

Omaliacycline (Nuzyra®) is a novel aminomethylcycline drug that was approved by the U.S. Food and Drug Administration (FDA) in 2018 and belongs to the tetracycline class of antimicrobial drugs. It can be used to treat community-acquired pneumonia and acute bacterial skin and soft tissue infections. The drug was developed and commercialized by Paratek Pharmaceuticals. Omaliacycline is a semi-synthetic compound derived from minocycline that can evade a wide range of resistance mechanisms, including efflux pumps and targeted protection mechanisms, and has been shown to be effective against a variety of bacteria. [1] Omaliacycline is the first intravenous and oral 9-aminomethylcycline drug to enter the clinical development stage for the treatment of a variety of infectious diseases, including acute bacterial skin and soft tissue infections (ABSSSI), community-acquired bacterial pneumonia (CABP), and urinary tract infections (UTI). This study determined the in vitro activity of omalicycline against a variety of Gram-positive clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), group A and B β-hemolytic streptococci, penicillin-resistant Streptococcus pneumoniae (PRSP), and Haemophilus influenzae. The MIC90 values of omalicycline against MRSA, VRE, and β-hemolytic streptococci were 1.0 μg/ml, 0.25 μg/ml, and 0.5 μg/ml, respectively, while the MIC90 values against PRSP and Haemophilus influenzae were 0.25 μg/ml and 2.0 μg/ml, respectively. Omalicycline is effective against pathogens exhibiting two main resistance mechanisms (ribosomal protection and active tetracycline efflux). The in vivo efficacy of omalicycline was confirmed using a mouse intraperitoneal infection model. A single intravenous injection of omaclocycline is effective against Streptococcus pneumoniae, Escherichia coli, and Staphylococcus aureus, including strains carrying tet(M) and tet(K) efflux genes, as well as methicillin-resistant Staphylococcus aureus (MRSA) strains. The median effective dose (ED50) against Streptococcus pneumoniae ranges from 0.45 mg/kg to 3.39 mg/kg, against Staphylococcus aureus from 0.30 mg/kg to 1.74 mg/kg, and against Escherichia coli from 2.02 mg/kg. These results demonstrate the drug's potent in vivo efficacy, including activity against strains containing common resistance determinants. Omaclocycline exhibits activity in vitro against a variety of Gram-positive bacteria and some Gram-negative pathogens, including strains containing resistance determinants, and this activity translates into potent efficacy in vivo. [2]

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- Omacycline is a semi-synthetic aminomethylcycline antibiotic, belonging to a subclass of tetracycline antibiotics, designed to overcome tetracycline resistance mechanisms (efflux pumps and ribosome protection) [1][2][3]
- Approved indications include acute bacterial skin and soft tissue infections (ABSSSI) and community-acquired bacterial pneumonia (CABP) in adults. It is available in both intravenous and oral formulations and can be used for sequential therapy [1][3][4]
- Once daily (intravenous: 300 mg initial dose, followed by 100 mg daily; oral: 450 mg initial dose, followed by 300 mg daily) [3][4]

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Omacycline (Nuzyra®) is a novel aminomethylcycline antibiotic, a semi-synthetic derivative of minocycline, which was approved by the U.S. Food and Drug Administration (FDA) in 2018 for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and soft tissue infections (ABSSSI). [1]
Compared to older generation tetracycline antibiotics, its main advantage lies in its ability to circumvent major tetracycline resistance mechanisms: ribosomal protection (e.g., mediated by Tet(M), Tet(O)) and efflux pumps (e.g., mediated by Tet(K), Tet(L)). It remains effective against a variety of multidrug-resistant bacteria. [1]
It is administered orally or intravenously once daily in the form of tosylate. [1]
Ongoing clinical trials are evaluating its use in the treatment of urinary tract infections (cystitis and acute pyelonephritis). [1]

C30H44N4O10S

652.76

652.277

C, 55.20; H, 6.79; N, 8.58; O, 24.51; S, 4.91

1196800-40-4

Omadacycline;389139-89-3;Omadacycline tosylate;1075240-43-5;Omadacycline hydrochloride;1196800-39-1;Omadacycline-d9;2272886-41-4

74891320

Solid powder

7

13

7

45

1230

4

CS(=O)(O)=O.O=C(C(C1=O)=C(O)[C@@H](N(C)C)[C@]2([H])C[C@]3([H])CC4=C(C(C3=C(O)[C@@]21O)=O)C(O)=C(CNCC(C)(C)C)C=C4N(C)C)N

BRTZQVQPPVIFKG-XGLFQKEBSA-N

InChI=1S/C29H40N4O7.CH4O3S/c1-28(2,3)12-31-11-14-10-17(32(4)5)15-8-13-9-16-21(33(6)7)24(36)20(27(30)39)26(38)29(16,40)25(37)18(13)23(35)19(15)22(14)34;1-5(2,3)4/h10,13,16,21,31,34-35,38,40H,8-9,11-12H2,1-7H3,(H2,30,39);1H3,(H,2,3,4)/t13-,16-,21-,29-;/m0./s1

(4S,4aS,5aR,12aR)-4,7-Bis(dimethylamino)-9-[(2,2-dimethylpropylamino)methyl]-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide; mesylate

PTK-0796; PTK 0796; PTK0796; (4S,4aS,5aR,12aR)-4,7-bis(dimethylamino)-9-[(2,2-dimethylpropylamino)methyl]-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide;methanesulfonic acid; PTK 0796 mesylate; Nuzyra; Amadacyclin;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)