Murepavadin (POL7080), a 14-amino acid (AA) cyclic peptide, is a highly effective and specific antibiotic. Murepavadin displays potent antimicrobial property against P. aeruginosa. The MIC50 and MIC90 values are both 0.12 mg/L. Murepavadin also targets lipopolysaccharide transporter D. Murepavadin may be utilized in the study of bacterial resistance.

Physicochemical Properties

Molecular Formula	C73H112N22O16
Molecular Weight	1553.81
Exact Mass	1552.862
CAS #	944252-63-5
Related CAS #	Murepavadin TFA
PubChem CID	91824766
Appearance	Typically exists as solid at room temperature
Density	1.4±0.1 g/cm3
Boiling Point	1894.3±65.0 °C at 760 mmHg
Flash Point	1099.4±34.3 °C
Vapour Pressure	0.0±0.3 mmHg at 25°C
Index of Refraction	1.660
LogP	-9.89
Hydrogen Bond Donor Count	22
Hydrogen Bond Acceptor Count	22
Rotatable Bond Count	21
Heavy Atom Count	111
Complexity	3200
Defined Atom Stereocenter Count	16
SMILES	C([C@@H]1NC(=O)[C@H]([C@H](O)C)NC(=O)C2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC2=CNC3C=CC=CC2=3)NC(=O)[C@H](CCN)NC(=O)[C@@H](CCN)NC(=O)[C@H](CCCN)NC(=O)[C@H](CCN)NC(=O)[C@H]([C@@H](C)CC)NC1=O)C1=CNC2C=CC=CC1=2
InChi Key	RIDRXGOBXZLKHZ-NZUANIILSA-N
InChi Code	InChI=1S/C73H112N22O16/c1-5-38(2)58-70(108)88-52(24-30-79)65(103)83-47(17-10-25-74)62(100)85-49(21-27-76)63(101)86-51(23-29-78)66(104)89-53(33-41-35-80-45-15-8-6-13-43(41)45)67(105)87-50(22-28-77)64(102)84-48(20-26-75)61(99)82-39(3)60(98)91-55(37-96)72(110)95-32-12-19-57(95)73(111)94-31-11-18-56(94)69(107)93-59(40(4)97)71(109)90-54(68(106)92-58)34-42-36-81-46-16-9-7-14-44(42)46/h6-9,13-16,35-36,38-40,47-59,80-81,96-97H,5,10-12,17-34,37,74-79H2,1-4H3,(H,82,99)(H,83,103)(H,84,102)(H,85,100)(H,86,101)(H,87,105)(H,88,108)(H,89,104)(H,90,109)(H,91,98)(H,92,106)(H,93,107)/t38-,39-,40+,47-,48-,49+,50-,51-,52-,53-,54-,55-,56-,57+,58-,59-/m0/s1
Chemical Name	(3R,9S,12S,15S,18S,21S,24S,27R,30S,33S,36S,39S,42S,45S)-15,18,24,27,33-pentakis(2-aminoethyl)-30-(3-aminopropyl)-36-[(2S)-butan-2-yl]-42-[(1R)-1-hydroxyethyl]-9-(hydroxymethyl)-21,39-bis(1H-indol-3-ylmethyl)-12-methyl-1,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazatricyclo[43.3.0.03,7]octatetracontane-2,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecone
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	MIC50: 0.12 mg/L(P. aeruginosa)[2] MIC90: 0.12 mg/L(P. aeruginosa)[2] IC50: 5.84 μM (gentamicin)[2]
ln Vitro	Murepavadin is active against P. aeruginosa, as evidenced by its 0.12 mg/L MIC50 and MIC90 values[2]. With an IC50 value of 5.84 μM, murepavadin inhibits the absorption of gentamicin by megalin in vitro[2].
ln Vivo	Murepavadin (sc; 0-100 mg/kg) is effective against infections caused by XDR isolates in pre-clinical animal models[2].
Animal Protocol	Animal/Disease Models: murine models of P. aeruginosa infection[2] Doses: 0-100 mg/kg Route of Administration: Subcutaneous, q24h or q12h Experimental Results: Resulted in an increase in survival rate to 100% and demonstrated Dramatically lower CFU levels both in the blood and in the peritoneal fluid at 2 and 10 mg/kg 1 h post-infection. Animal/Disease Models: Mouse, rat, rabbit, and monkey[2] Doses: 0-5 mg/kg Route of Administration: intraperitoneal (ip)or subcutaneous, single Experimental Results: Followed a two-compartment model following intravenous (iv)administration and decline of plasma concentrations. Distributed into the aqueous phase of the body, and systemic plasma clearance (CL) values were similar to the species-specific glomerular filtration rates (GFRs) . Had high bioavailability (67.79%) after subcutaneous (sc)( sc) administration in rats but had low oral bioavailability (<0.01%). Had a linear relationship between ELF AUC and unbound plasma AUC in mouse. Did not readily cross the blood/brain barrier.
References	[1]. New antibiotics for ventilator-associated pneumonia. Curr Opin Infect Dis. 2018 Jan 13. [2]. Murepavadin: a new antibiotic class in the pipeline. Expert Rev Anti Infect Ther. 2018 Apr;16(4):259-268.
Additional Infomation	Murepavadin is under investigation in clinical trial NCT02110459 (Pharmacokinetics and Safety of POL7080 in Patients With Renal Impairment).

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

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. Injection Formulations (e.g. IP/IV/IM/SC) 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). 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) Oral Formulations 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). 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 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	0.6436 mL	3.2179 mL	6.4358 mL
	5 mM	0.1287 mL	0.6436 mL	1.2872 mL
	10 mM	0.0644 mL	0.3218 mL	0.6436 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.