Tetracycline
55 clinical isolates of C. acnes are inhibited by seromycin. The drug's MIC values ranged from 0.5 to 16 µg/ml; the MIC50 was 0.5 µg/ml and the MIC90 was 4 µg/ml.Sarecycline works against organisms that are resistant to macrolides[1].
When it comes to enteric aerobic Gram-negative bacteria, serocycline hydrochloride shows very little activity[2].

55 clinical isolates of C. acnes are inhibited by seromycin. The drug's MIC values ranged from 0.5 to 16 µg/ml; the MIC50 was 0.5 µg/ml and the MIC90 was 4 µg/ml.Sarecycline works against organisms that are resistant to macrolides[1].
When it comes to enteric aerobic Gram-negative bacteria, serocycline hydrochloride shows very little activity[2].

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Sarecycline demonstrated in vitro activity against 55 clinical isolates of Cutibacterium acnes (formerly Propionibacterium acnes), with an MIC range of 0.5 to 16 µg/mL, an MIC50 of 0.5 µg/mL, and an MIC90 of 4 µg/mL. This activity was comparable to tetracycline, doxycycline, and minocycline. It also remained active against a subset of C. acnes isolates with high-level resistance to erythromycin (MIC ≥128 µg/mL). [1]
Against aerobic Gram-positive cocci, Sarecycline showed activity against methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MIC90: 0.5 µg/mL for both). For Staphylococcus epidermidis, the MIC90 was 2 µg/mL. It was more active than tetracycline and doxycycline against Staphylococcus haemolyticus (MIC90: 2 µg/mL). For Streptococcus pyogenes and Streptococcus agalactiae, MIC90 values were 8 µg/mL and 16 µg/mL, respectively. [1]
For Enterococcus faecalis (vancomycin-susceptible), Sarecycline had limited activity with an MIC90 of 32 µg/mL. Against Enterococcus faecium (both vancomycin-susceptible and -resistant), MIC90 values ranged from 16 to 32 µg/mL. [1]
Against aerobic Gram-negative bacilli (Enterobacteriaceae), Sarecycline was significantly less active than broad-spectrum tetracyclines. For Escherichia coli, the MIC90 was >64 µg/mL (vs. 2-32 µg/mL for comparators). For Klebsiella pneumoniae, the MIC90 was >64 µg/mL. It was largely inactive against Proteus mirabilis (MIC >64 µg/mL). Against a separate collection of contemporary Enterobacteriaceae isolates (from patients aged 11-40), Sarecycline showed reduced potency (16- to 32-fold lower based on MIC50 comparisons) compared to minocycline and doxycycline. [1]
Against representative Gram-positive anaerobic bacteria (e.g., Bifidobacterium spp., Clostridium spp., Lactobacillus spp.), Sarecycline showed a 4- to 8-fold reduced potency compared to doxycycline based on MIC distribution plots. Against Gram-negative anaerobes (e.g., Bacteroides spp., Prevotella spp.), Sarecycline was the least active tetracycline tested. [1]
In macromolecular biosynthesis assays using S. aureus ATCC 29213, Sarecycline inhibited protein synthesis in a concentration-dependent manner, reaching about 80% inhibition at 8 times the MIC. It had minimal effects on DNA, RNA, lipid, and cell wall synthesis at these concentrations. [1]
Spontaneous mutation frequency studies for Sarecycline against C. acnes showed low frequencies (approximately 10^-10) at 4x and 8x MIC, similar to minocycline and vancomycin. Against S. aureus and S. epidermidis, frequencies ranged from 10^-9 to 10^-8 at 4x and 8x MIC, similar to vancomycin. [1]
Against tetracycline-resistant S. aureus strains, Sarecycline was more active than tetracycline against strains carrying the efflux gene tet(K) (MIC range: 0.125-1 µg/mL vs. 16-64 µg/mL for tetracycline). However, its activity was decreased against strains carrying the ribosomal protection gene tet(M) (MIC: 8 µg/mL) or both tet(M) and tet(38) (MIC: 16-32 µg/mL). [1]

In a mouse model of neutropenic thigh infection, sarecycline hydrochloride (0.33–9 mg/kg; intravenous) exhibits strong efficacy against S. aureus[1]..

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In a murine systemic intraperitoneal infection model, a single subcutaneous dose of Sarecycline showed efficacy against S. aureus RN450-1 with a 50% protective dose (PD50) of 0.25 mg/kg, comparable to doxycycline (PD50: 0.3 mg/kg) and less potent than minocycline (PD50: 0.03 mg/kg). [1]
In the same model against Escherichia coli PBS1478, Sarecycline did not demonstrate efficacy even at the highest tested dose of 40 mg/kg (PD50 >40 mg/kg), whereas doxycycline and minocycline had PD50 values of 5.72 mg/kg and 6.95 mg/kg, respectively. [1]
In a murine neutropenic thigh infection model with S. aureus RN450-1, Sarecycline administered intravenously achieved a 2-log10 reduction in bacterial burden with an ED50 of 8.23 mg/kg, comparable to doxycycline (ED50: 8.31 mg/kg). [1]

The primary cell-based assays described are standard antimicrobial susceptibility tests. For anaerobic bacteria (including C. acnes), the reference agar dilution method was used according to guidelines. Bacteria were grown on appropriate agar plates (e.g., brucella agar for C. acnes) under anaerobic conditions. Serial dilutions of antibiotics were incorporated into the agar. Plates were inoculated with standardized bacterial suspensions and incubated anaerobically (e.g., 48 hours at 35°C for C. acnes). The MIC was defined as the lowest concentration inhibiting visible growth. [1]
For aerobic bacteria, the reference broth microdilution (BMD) method was used. Serial two-fold dilutions of antibiotics were prepared in cation-adjusted Mueller-Hinton broth in microtiter plates. Bacterial suspensions were adjusted to a 0.5 McFarland standard and diluted to a final inoculum density. The diluted suspension was added to the wells. Plates were incubated aerobically (e.g., 18-24 hours at 35°C), and the MIC was read as the lowest concentration with no visible growth. [1]
Macromolecular biosynthesis assays were performed in S. aureus ATCC 29213 cultures grown to early exponential phase. To assess effects on DNA, RNA, or protein synthesis, cultures containing Sarecycline (at multiples of the MIC) were incubated for 5 minutes before adding radiolabeled precursors ([³H]thymidine, [³H]uridine, or [³H]leucine). Reactions proceeded for 15-30 minutes at room temperature and were stopped by adding cold trichloroacetic acid. Precipitates were collected, and radioactivity was measured using a liquid scintillation counter. For cell wall and lipid synthesis, similar procedures were followed using [³H]N-acetylglucosamine and [³H]glycerol as precursors, respectively. [1]

Animal Model: Female SD-1 mice (A murine neutropenic thigh wound infection model)[1]
Dosage: 0.33, 1, 3, or 9 mg/kg
Administration: Intravenously
Result: at a dose similar to doxycycline, achieved a 2-log10 reduction in the bacterial burden in the thigh (ED50s of 8.23 and 8.32 mg/kg, respectively).

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1. Murine Systemic Intraperitoneal Infection Model: Six-week-old, specific-pathogen-free, male CD-1 mice (up to 30 g) were used. For S. aureus RN450-1 infection, bacteria were grown overnight in Mueller-Hinton broth to ~1x10^9 CFU/mL, diluted in phosphate-buffered saline (PBS), and mixed with a 5% bacteriological mucin suspension. Mice were infected intraperitoneally with 3.5x10^8 to 7.4x10^8 CFU. For E. coli PBS1478 infection, a similar process was used, with an inoculum of 6.5x10^7 to 1.6x10^8 CFU. At 1 hour post-infection, mice were treated subcutaneously with a single dose of Sarecycline, doxycycline, or minocycline dissolved in sterile water. Doses were adjusted for the active moiety percentage. Doses ranged from 0.01 to 0.5 mg/kg for S. aureus studies and from 0.5 to 40 mg/kg for E. coli studies. Survival was monitored for 48 hours to determine the PD50 (dose required for 50% survival). [1]
2. Murine Neutropenic Thigh Infection Model: Female SD-1 mice were rendered neutropenic by intraperitoneal injections of cyclophosphamide (150 mg/kg on day -4 and 100 mg/kg on day -1). On day 0, mice were infected by intramuscular injection of 1x10^6 CFU of S. aureus RN450-1 into the left thigh. At 2 and 6 hours post-infection, mice were treated intravenously with Sarecycline or doxycycline at doses of 0.33, 1, 3, or 9 mg/kg in sterile water. At 24 hours post-infection, thighs were removed, homogenized, and plated on trypticase soy agar with 5% sheep blood to determine bacterial burden. The ED50 was defined as the dose required to achieve a 2-log10 reduction in CFU compared to the untreated control. [1]

Seracycline is taken orally once daily at a dose of 1.5 mg/kg, either on an empty stomach or with food, as food intake has no effect on its bioavailability. It is less likely to cross the blood-brain barrier than other tetracyclines. Specific pharmacokinetic parameters, such as half-life, oral bioavailability, absorption, distribution, metabolism, and excretion, have not yet been provided. [2]

In the phase III study, the most common adverse events included nausea (3.2% in the saracycline group and 1.7% in the placebo group), nasopharyngitis, headache, and vomiting. Vulvovaginal candidiasis/fungal infection was reported in 1.1% to 1.2% of subjects treated with saracycline. No significant increase in phototoxicity, dizziness, pseudotumor cerebri, tinnitus, vertigo, or esophagitis was observed compared with the placebo group. [2]

[1]. Antimicrob Agents Chemother. 2018;63(1):e01297-18.

[2]. Future Microbiol. 2019;14(14):1235-1242.

[3]. Proc Natl Acad Sci U S A. 2020;117(34):20530-20537.

[4]. J Drugs Dermatol.2018 Mar 1;17(3):333-338.

See also: Saracycline hydrochloride (note moved to).

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Saracycline is described as the first narrow-spectrum tetracycline antibiotic specifically for the treatment of moderate to severe acne vulgaris. It is an oral aminomethylcycline with a unique modification at the C-7 site. [1]
It has completed two Phase III clinical trials, achieving the primary efficacy endpoint of 12 weeks for the treatment of acne. [1]
Compared to broad-spectrum tetracyclines such as doxycycline and minocycline, it has narrow-spectrum antibacterial activity and lower antibacterial activity against aerobic Gram-negative bacteria and anaerobic bacteria in the gut, and is therefore thought to potentially reduce disruption to the gut microbiota and its associated adverse effects (e.g., diarrhea, candidiasis). [1]
The drug’s antibacterial effect against Propionibacterium acnes is achieved by inhibiting protein synthesis, which may also downregulate the production of inflammatory proteins/enzymes, thereby producing an anti-inflammatory effect. [1]

C24H30CLN3O8

523.97

523.172

C, 55.02; H, 5.77; Cl, 6.77; N, 8.02; O, 24.43

1035979-44-2

Sarecycline;1035654-66-0

71296095

Light yellow to yellow solid powder

1.908

6

10

5

36

1010

4

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])([H])N(C([H])([H])[H])OC([H])([H])[H])C([H])=C([H])C(=C3C(=C1C2=O)O[H])O[H])N(C([H])([H])[H])C([H])([H])[H])=O)O[H]

APPRLAGZQKOUFL-FIPJBXKNSA-N

InChI=1S/C24H29N3O8.ClH/c1-26(2)18-13-8-11-7-12-10(9-27(3)35-4)5-6-14(28)16(12)19(29)15(11)21(31)24(13,34)22(32)17(20(18)30)23(25)33;/h5-6,11,13,18,28,30-31,34H,7-9H2,1-4H3,(H2,25,33);1H/t11-,13-,18-,24-;/m0./s1

(4S,4aS,5aR,12aS)-4-(dimethylamino)-3,10,12,12a-tetrahydroxy-7-((methoxy(methyl)amino)methyl)-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide hydrochloride

WC-3035 HCl; WC 3035 hydrochloride; WC3035; P005672 hydrochloride; P-005672; P 005672; P005672; trade name: Seysara

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, avoid exposure to moisture.

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

DMSO : ~100 mg/mL (~190.85 mM)

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.)