Tetracycline; protein synthesis of bacteria; Bacterial 30S ribosomal subunit (binds to the A site of the 30S subunit, inhibiting protein synthesis) [1][2][3]

- 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 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.

- 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 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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Omadacycline demonstrates broad-spectrum in vitro antibacterial activity. Minimal Inhibitory Concentration (MIC) testing was performed against various bacterial strains, including those with known resistance genes. Against Gram-positive bacteria: For Staphylococcus aureus carrying the tet(M) gene, the MIC range was 0.125–1 µg/mL; for strains carrying tet(K), the MIC range was 0.125–0.25 µg/mL. For multidrug and methicillin-resistant S. aureus (MRSA), the MIC range was 0.25–0.5 µg/mL (MIC50 and MIC90 both 0.5 µg/mL). For Enterococcus faecalis and E. faecium (including vancomycin-resistant strains), MICs were as low as 0.125–0.5 µg/mL against ribosomal protection strains (tet(M), tet(S)) and 0.25 µg/mL against efflux strains (tet(L)). For Streptococcus pneumoniae (including penicillin- and multidrug-resistant strains), MIC values were ≤0.06 µg/mL. For S. pyogenes and S. agalactiae (beta-hemolytic streptococci), the MIC range was ≤0.06–0.5 µg/mL. Against Gram-negative bacteria: For Escherichia coli carrying the tet(A) efflux gene, the MIC was 2 µg/mL. For Haemophilus influenzae and Klebsiella pneumoniae, MIC50 values were 1 µg/mL and 2 µg/mL, respectively. Activity was also shown against anaerobes (e.g., Clostridium difficile MIC range 0.25-8 µg/mL), atypical pathogens (e.g., Legionella pneumophila MIC range 0.06–1 µg/mL; Chlamydia pneumoniae MIC range 0.03–0.5 µg/mL), Mycoplasma spp. (e.g., M. hominis MIC50 0.032 µg/mL, MIC90 0.063 µg/mL), and rapidly growing mycobacteria (e.g., Mycobacterium abscessus MIC50 1 µg/mL, MIC90 2 µg/mL). [1]

- 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 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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he clinical efficacy of omadacycline was demonstrated in human Phase II and III trials. For acute bacterial skin and skin structure infections, in the OASIS-1 and OASIS-2 studies, intravenous (IV) or oral omadacyclinewas non-inferior to linezolid, with high clinical success rates against pathogens including MRSA andE. faecalis. For community-acquired bacterial pneumonia, in the OPTIC study, IV omadacycline was non-inferior to moxifloxacin. [1]

In vitro stability and drug–drug interaction potential of omadacycline[6]
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.

- 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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Omadacycline MIC90s for MRSA, VRE, and beta-hemolytic streptococci are 1.0 μg/mL, 0.25 μg/mL, and 0.5 μg/mL, correspondingly. For PRSP and H. influenzae, the corresponding omadacycline MIC90s are 0.25 μg/ml and 2.0 μg/mL. Omadacycline exhibits efficacy against organisms that exhibit both ribosomal protection and active tetracycline efflux, the two main mechanisms of resistance[1]. Omadacycline has little effect on the synthesis of DNA, RNA, or peptidoglycans, but it inhibits the synthesis of proteins. Furthermore, omadacycline exhibits enhanced binding, comparable to tigecycline, to the tetracycline binding site on the 30S subunit of the bacterial ribosome due to additional molecular interactions.

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The minimum inhibitory concentration (MIC) was determined using the broth microdilution method according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Bacterial isolates were subcultured twice onto appropriate solid medium prior to testing. Testing was performed in Mueller-Hinton broth, with horse or sheep blood supplementation for fastidious organisms. The MIC was defined as the lowest concentration inhibiting visible growth. [2]
A multiplex PCR assay was used to detect and identify tetracycline resistance genes (tet(K), tet(L), tet(A), tet(B), tet(M), tet(O), tet(S)) in bacterial isolates. [2]

- 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]
- 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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Systemic 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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A systemic intraperitoneal (i.p.) challenge model in mice was used to evaluate efficacy.
Six-week-old, specific-pathogen-free, male CD-1 mice (weighing 18–30 g) were acclimated for one week.
Bacteria (S. pneumoniae, S. aureus, or E. coli) were grown to approximately 1×10⁹ CFU/ml, serially diluted in sterile PBS, and the infectious dose confirmed by plating.
Septicemia was induced by i.p. injection of 500 µL of bacterial suspension in 4.5% bacteriological mucin. The infectious doses for different strains are specified in the document (e.g., ~6.85×10⁵ CFU/mouse for S. pneumoniae PBS1339).
At 1 hour post-infection, mice were treated intravenously (i.v.) with a single dose of omadacycline or comparator antibiotics. Drugs were dissolved in sterile saline and administered at a volume of 10 ml/kg. Doses were freshly formulated and adjusted for percent activity. Tested dose ranges were typically from 0.11 to 18 mg/kg (with some exceptions from 0.08 to 54 mg/kg).
Each experiment included at least four dose levels with 5 mice per group, plus an untreated control group.
Mice were monitored for morbidity every 24 hours for 7 days. The 50% effective dose (ED₅₀), defined as the dose required for 50% survival at 7 days post-infection, was calculated using nonlinear regression analysis. [2]

Absorption: The oral bioavailability of omalicycline in humans is approximately 34%. Food has little effect on absorption, but antacids and iron supplements can reduce absorption through chelation [1][3]
- Distribution: Large volume of distribution (160-230 liters), high tissue permeability (e.g., skin blister fluid, lung tissue), and its concentration is higher than that in plasma [3]
- Metabolism: Very little metabolism; approximately 95% of the drug is excreted unchanged [3]
- Excretion: Primarily excreted via the kidneys (35-45%) and non-renal routes (55-65%), with a terminal half-life of approximately 16-18 hours [1][3]

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The pharmacokinetics of omalicycline best fits a linear three-compartment model, with zero-order kinetics for intravenous infusion and first-order kinetics for oral administration, and the transport compartment is taken into account to explain delayed absorption. Omacycline has a volume of distribution (Vd) of 190 to 204 L, a terminal elimination half-life (t½) of 13.5 to 17.1 hours, a total clearance (CLT) of 8.8 to 10.6 L/h, and a protein binding rate of 21.3% in healthy subjects. The estimated oral bioavailability of omacycline is 34.5%. Following a single oral dose of 300 mg (bioequivalent to 100 mg intravenously) of omacycline in fasting subjects, the peak plasma concentration (Cmax) ranged from 0.5 to 0.6 mg/L, and the area under the plasma concentration-time curve (AUC0-∞) ranged from 9.6 to 11.9 mg·h/L. The ratio of the plasma area under the drug concentration-time curve to the minimum inhibitory concentration (fAUC24h/MIC) has been established as a pharmacodynamic parameter for predicting the antibacterial efficacy of omacycline. 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), respectively. Currently, omalicycline has been approved by the U.S. Food and Drug Administration (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 associated with the use of omalicycline. Based on clinical trial data to date, the adverse reaction profile of omalicycline is similar to that of the control drugs linezolid and moxifloxacin studied. Unlike tigecycline and eracycline, omalicycline is available in oral formulations, allowing for a gradual transition from intravenous to oral formulations, which may help patients be discharged earlier, receive outpatient treatment, and save costs. Omalicycline has potential applications 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 bacteria. [https://pubmed.ncbi.nlm.nih.gov/31970713/]

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A phase I clinical study investigated the pharmacokinetics and dosage of oral and intravenous omalicycline. Both routes of administration showed good tolerability. The specific pharmacokinetic parameters (e.g., half-life, oral bioavailability, absorption, distribution, metabolism, excretion) are not detailed in this reference [1].

Toxicity/Toxicokinetics - Plasma protein binding: ~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 showed that omalicycline had no significant inhibitory effect on human ether-a-go-go-related gene (hERG) channels (IC50 >300 μM). In vivo telemetry studies in dogs showed 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 recommends against breastfeeding during treatment and for 4 days after the last dose. If the infant is being breastfed, the infant's gut microbiota should be closely monitored for any impact, such as diarrhea, candidiasis (e.g., thrush, diaper rash), or rare hematochezia (suggesting possible antibiotic-associated colitis). As a theoretical precaution, breastfeeding women should avoid prolonged or repeated use of the drug.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

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In a Phase I study, intravenous doses of omalicycline exceeding 300 mg resulted in a reversible increase in alanine aminotransferase. Oral doses exceeding 400 mg resulted in mild nausea. 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 and transient and did not lead to withdrawal from the trial. [1]

[1]. Omadacycline: A Newly Approved Antibacterial from the Class of Tetracyclines. Pharmaceuticals (Basel). 2019 Apr 21;12(2):63.

[2]. In vitro and in vivo antibacterial activities of omadacycline, a novel aminomethylcycline. Antimicrob Agents Chemother. 2014;58(2):1127-35.

[3]. Omadacycline: A Novel Oral and Intravenous Aminomethylcycline Antibiotic Agent. Drugs. 2020 Feb;80(3):285-313.

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

[5]. In Vitro and In Vivo Assessments of Cardiovascular Effects with Omadacycline. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5247-53.

[6]. Discovery, pharmacology, and clinical profile of omadacycline, a novel aminomethylcycline antibiotic. Bioorg Med Chem.2016 Dec 15;24(24):6409-6419.

Omadacycline is a semi-synthetic aminomethylcycline antibiotic, a subclass of tetracycline antibiotics, designed to overcome tetracycline resistance mechanisms (efflux pumps and ribosomal 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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Omadacycline (Nuzyra®) is a novel aminomethylcycline antibiotic, a semi-synthetic derivative of minocycline, which was approved by the FDA in October 2018. It is administered as a tosylate salt, once daily orally or intravenously. It is indicated for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and soft tissue infections. Its main advantage lies in its ability to evade extensive efflux and ribosomal protection resistance mechanisms, thereby maintaining activity against a wide range of Gram-positive, Gram-negative, anaerobic, and atypical bacteria, including many drug-resistant strains. Clinical trials are currently underway for its use in the treatment of urinary tract infections (cystitis and acute pyelonephritis). [1]

C36H48N4O10S

728.86

728.309

C, 59.33; H, 6.64; N, 7.69; O, 21.95; S, 4.40

1075240-43-5

Omadacycline;389139-89-3;Omadacycline hydrochloride;1196800-39-1;Omadacycline-d9;2272886-41-4;Omadacycline mesylate;1196800-40-4

54746485

White to yellow solid powder

4.736

7

13

8

51

1350

4

S(C1C([H])=C([H])C(C([H])([H])[H])=C([H])C=1[H])(=O)(=O)O[H].O([H])[C@@]12C(=C(C(N([H])[H])=O)C([C@]([H])([C@]1([H])C([H])([H])[C@]1([H])C([H])([H])C3=C(C([H])=C(C([H])([H])N([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C(=C3C(=C1C2=O)O[H])O[H])N(C([H])([H])[H])C([H])([H])[H])N(C([H])([H])[H])C([H])([H])[H])=O)O[H]

SETFNHZTVGTBHC-XGLFQKEBSA-N

InChI=1S/C29H40N4O7.C7H8O3S/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;1-6-2-4-7(5-3-6)11(8,9)10/h10,13,16,21,31,34,36-37,40H,8-9,11-12H2,1-7H3,(H2,30,39);2-5H,1H3,(H,8,9,10)/t13-,16-,21-,29-;/m0./s1

(4S,4aS,5aR,12aS)-4,7-bis(dimethylamino)-3,10,12,12a-tetrahydroxy-9-((neopentylamino)methyl)-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide 4-methylbenzenesulfonate

PTK 0796 tosylate; PTK-0796; PTK0796; Omadacycline (tosylate); Omadacycline tosylate [USAN]; Omadacycline tosilate; Amadacyclintosylate

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)

DMSO : 12.5 100 mg/mL ( 137.2 mM )
Water : 100 mg/mL
Ethanol : 100 mg/mL

Solubility in Formulation 1: 50 mg/mL (68.60 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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