Mean MIC: 125 ng/mL (E. coli)[1] MIC50: 1 mg/mL (A. baumannii)[2] MIC90: 2 mg/mL (A. baumannii)[2]

With IC50s of 4.72±0.54 and 3.06±0.85 μM (freshly generated), tigecycline (0.63-30 µM, preincubated for 4 days, administered for 72 hours) inhibits AML2 cells and HL-60 cells. After one day of preincubation, tigecycline inhibits HL-60 and AML2 cells with IC50 values of 4.27±0.45 and 5.64±0.55 μM, respectively. 60 cells exhibited 3.95±0.39 μM and 4.09±0.41 μM IC50s (three days preincubation). Tigecycline reduced its capacity to kill TEX human leukemia cells after 4 days of preincubation in saline, as shown by the CellTiter Flour assay. IC50~5 µM when freshly synthesized to IC50 >50 µM after 4 days of preincubation[1].

In NOD/SCID mice, tigecycline (50 mg/kg) administered intraperitoneally twice a day for 11 days decreases tumor mass and volume[1]. Tigecycline in saline has the following values: peak plasma concentration (Cmax), terminal half-life (t1/2), area under the plasma concentration-time curve (AUC), clearance (CL), and volume of distribution (Vz), in that order: 22.8μg/mL, 108.9 min, 1912.2min*μg/mL, 26.1 mL/min/kg, and 4109.4 mL/kg. For Tigecycline in formulation (60 mg/mL pyruvate, 3 mg/mL ascorbic acid, pH 7 in saline), the peak plasma concentration (Cmax), the terminal half-life (t1/2), the area under the plasma concentration-time curve (AUC), the clearance (CL), and the volume of distribution (Vz) are 15.7μg/mL, 110.3 min, 2036.5 min*μg/mL, 24.6 mL/min/kg, and 3906.2 mL/kg, respectively.

Cell Viability Assay[1]
Cell Types: Human leukemic OCI-AML2, HL-60(ATCC) and TEX cell lines
Tested Concentrations: 0.63-30 µM
Incubation Duration: Preincubated for 4 days, treated for 72 hrs (hours)
Experimental Results: Inhibited AML2 cells and HL-60 cells with IC50s of 4.72±0.54 and 3.06±0.85 μM(freshly prepared).

Animal/Disease Models: NOD/SCID (severe combined immunodeficient) mouse with OCI-AML2 acute myeloid leukemia (AML) xenograft model[1]
Doses: 50 mg/kg
Route of Administration: intraperitoneal (ip)injection; twice a day; for 11 days
Experimental Results: decreased tumor volume and weight .

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Animal/Disease Models: NOD/SCID (severe combined immunodeficient) mouse[1]
Doses: 50 mg/kg
Route of Administration: intraperitoneal (ip)injection; 360 minutes
Experimental Results: The peak plasma concentration (Cmax), the terminal half-life (t1/2), area under the plasma concentration -time curve (AUC), clearance (CL) and volume of distribution (Vz) are 22.8 μg/mL, 108.9 min, 1912.2 min*μg/mL, 26.1 mL/min/kg, 4109.4 mL/kg, respectively.

[1]. Jitkova Y, et al. A novel formulation of tigecycline has enhanced stability and sustained antibacterial and antileukemic activity. PLoS One. 2014 May 28;9(5):e95281.
[2]. Falagas ME, et al. Activity of TP-6076 against carbapenem-resistant Acinetobacter baumannii isolates collected from inpatients in Greek hospitals. Int J Antimicrob Agents. 2018 Aug;52(2):269-271.

Tigecycline is a tetracycline derivative with its 5-hydroxyl and 6-methyl groups replaced by hydrogen atoms, and its 7- and 9-positions replaced by dimethylamino and (N-tert-butylglycyl)amino groups, respectively. It is a glycylcycline antibiotic with antibacterial activity against a variety of Gram-positive and Gram-negative bacteria, including tetracycline-resistant bacteria. It is used intravenously to treat complicated skin and soft tissue infections caused by susceptible bacteria. It is an antibacterial drug. It belongs to the tetracycline class of compounds and is a tert-α-hydroxy ketone. It is the conjugate base of tigecycline (1+). Tigecycline is a tetracycline antibacterial drug. It is a tetracycline derivative and can act as a protein synthesis inhibitor. It is used as a systemic antibacterial drug to treat complicated skin and intra-abdominal infections. Tigecycline is also used to treat community-acquired pneumonia. Tigecycline is a broad-spectrum, first-in-class glycylcycline antibiotic currently used to treat complicated skin infections, intra-abdominal infections, and community-acquired pneumonia. Furthermore, we have demonstrated that tigecycline possesses in vitro and in vivo anti-acute myeloid leukemia (AML) activity, attributed to its ability to inhibit mitochondrial translation. Tigecycline is relatively unstable after reconstitution, and this instability may limit its application in outpatient infusion therapy for infections and may hinder the development of optimal dosing regimens for AML. This study aimed to find a formulation that could improve the stability of the drug after reconstitution while maintaining its antibacterial and antileukemic activities. We tested a range of chemical additives to screen for excipients that could improve the stability of tigecycline solutions at room temperature for up to one week. We discovered a novel formulation containing the oxygen reducing agent ascorbic acid (3 mg/mL) and pyruvate (60 mg/mL) in physiological saline at pH 7.0, in which tigecycline (1 mg/mL) remains intact for at least 7 days under light-protected conditions. This formulation also maintained the drug's antibacterial and antileukemic activities in vitro. Furthermore, this novel formulation also preserved the antileukemic activity of tigecycline in vivo. Therefore, we identified and characterized a novel tigecycline formulation that retains its stability and efficacy after reconstitution. [1]

C33H55N5O20S4

969.2323

Tigecycline;220620-09-7;Tigecycline hydrochloride;197654-04-9;Tigecycline mesylate;1135871-27-0;Tigecycline hydrate;1229002-07-6

137628652

Typically exists as Light yellow to yellow solid at room temperature

IBOQJGSRFKTAPT-LFSRUXGMSA-N

InChI=1S/C29H39N5O8.4CH4O3S/c1-28(2,3)31-11-17(35)32-15-10-16(33(4)5)13-8-12-9-14-21(34(6)7)24(38)20(27(30)41)26(40)29(14,42)25(39)18(12)23(37)19(13)22(15)36;4*1-5(2,3)4/h10,12,14,21,31,36-37,40,42H,8-9,11H2,1-7H3,(H2,30,41)(H,32,35);4*1H3,(H,2,3,4)/t12-,14-,21-,29-;;;;/m0..../s1

(4S,4aS,5aR,12aR)-9-[[2-(tert-butylamino)acetyl]amino]-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide;methanesulfonic acid

Tigecycline tetramesylate; GAR-936 tetramesylate; Tigecycline (tetramesylate);

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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 (~103.09 mM)
H2O :~50 mg/mL (~51.54 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.)