PF-5081090 | CAS#1312473-63-4 | LpxC inhibitor

MedKoo Cat#: 531333 | Name: PF-5081090

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

PF-5081090 is a potent inhibitor of LpxC, a metalloenzyme required for the synthesis of lipid A, an essential component of the outer membrane of Gram-negative bacteria. The IC50 for enzyme inhibition is 1.1 nM and the minimal inhibitory concentration (MIC) for inhibiting growth of Pseudomonas aeruginosa growth is 0.008 mg/mL.

Chemical Structure

PF-5081090

CAS#1312473-63-4

Theoretical Analysis

MedKoo Cat#: 531333

Name: PF-5081090

CAS#: 1312473-63-4

Chemical Formula: C18H21FN2O6S

Exact Mass: 412.1104

Molecular Weight: 412.43

Elemental Analysis: C, 52.42; H, 5.13; F, 4.61; N, 6.79; O, 23.28; S, 7.77

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 550.00	2 Weeks
25mg	USD 1,225.00	2 Weeks

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Related CAS #

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Synonym

PF-5081090; PF 5081090; PF5081090; PF-05081090, PF05081090, PF 05081090

IUPAC/Chemical Name

(2R)-4-[4-(2-Fluoro-4-methoxyphenyl)-2-oxo-2H-pyridin-1-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

InChi Key

DNVUWHWBCMGQLU-GOSISDBHSA-N

InChi Code

InChI=1S/C18H21FN2O6S/c1-18(17(23)20-24,28(3,25)26)7-9-21-8-6-12(10-16(21)22)14-5-4-13(27-2)11-15(14)19/h4-6,8,10-11,24H,7,9H2,1-3H3,(H,20,23)/t18-/m1/s1

SMILES Code

O=C(NO)[C@@](S(=O)(C)=O)(C)CCN1C=CC(C2=CC=C(OC)C=C2F)=CC1=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

PF-5081090 (LpxC-4) is a potent LpxC inhibitor, is a rapidly bactericidal with broad-spectrum activity.

In vitro activity:

As shown in Table 2, 32 mg/liter of PF-5081090 resulted in increased susceptibility to rifampin in all strains, with all strains demonstrating an MIC of ≤0.03 in the presence of the LpxC inhibitor, representing a more than 1,000-fold reduction in the case of two strains demonstrating rifampin MICs of 32 mg/liter in the absence of inhibitor. PF-5081090 also increased susceptibility to vancomycin and azithromycin, resulting in reductions in MICs of between 8- and 16-fold for all strains except Ab-84, which did not demonstrate increased susceptibility to azithromycin in the presence of PF-5081090 (Table 2). Reference: Antimicrob Agents Chemother. 2016 Jul 22;60(8):5076-9. https://pubmed.ncbi.nlm.nih.gov/27270288/

In vivo activity:

Efficacy of LpxC-4 in an acute (48-h) mouse pneumonia model was achieved against PA-1950 with an ED50 of <25 mg/kg. This result was consistent with an estimated LpxC-4 ED50 of 16.8 mg/kg against PA-1950 in the neutropenic thigh model. Normalizing the dose to free drug exposure and considering an MIC of 0.25 µg/ml, the ED50s in the thigh and lung endpoint studies correspond to free AUC/MICs of 7.2 and 10.7, respectively, suggesting similar exposure requirements for both models. Reference: mBio. 2014 Sep 30;5(5):e01551-14. https://pubmed.ncbi.nlm.nih.gov/25271285/

Preparing Stock Solutions

The following data is based on the product molecular weight 412.43 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. García-Quintanilla M, Caro-Vega JM, Pulido MR, Moreno-Martínez P, Pachón J, McConnell MJ. Inhibition of LpxC Increases Antibiotic Susceptibility in Acinetobacter baumannii. Antimicrob Agents Chemother. 2016 Jul 22;60(8):5076-9. doi: 10.1128/AAC.00407-16. PMID: 27270288; PMCID: PMC4958213. 2. Tomaras AP, McPherson CJ, Kuhn M, Carifa A, Mullins L, George D, Desbonnet C, Eidem TM, Montgomery JI, Brown MF, Reilly U, Miller AA, O'Donnell JP. LpxC inhibitors as new antibacterial agents and tools for studying regulation of lipid A biosynthesis in Gram-negative pathogens. mBio. 2014 Sep 30;5(5):e01551-14. doi: 10.1128/mBio.01551-14. PMID: 25271285; PMCID: PMC4196226.

In vitro protocol:

In vivo protocol:

1. Tomaras AP, McPherson CJ, Kuhn M, Carifa A, Mullins L, George D, Desbonnet C, Eidem TM, Montgomery JI, Brown MF, Reilly U, Miller AA, O'Donnell JP. LpxC inhibitors as new antibacterial agents and tools for studying regulation of lipid A biosynthesis in Gram-negative pathogens. mBio. 2014 Sep 30;5(5):e01551-14. doi: 10.1128/mBio.01551-14. PMID: 25271285; PMCID: PMC4196226.

1: García-Quintanilla M, Caro-Vega JM, Pulido MR, Moreno-Martínez P, Pachón J, McConnell MJ. Inhibition of LpxC Increases Antibiotic Susceptibility in Acinetobacter baumannii. Antimicrob Agents Chemother. 2016 Jul 22;60(8):5076-9. doi: 10.1128/AAC.00407-16. Print 2016 Aug. PubMed PMID: 27270288; PubMed Central PMCID: PMC4958213. Niu Z, Lei P, Wang Y, Wang J, Yang J, Zhang J. Small molecule LpxC inhibitors against gram-negative bacteria: Advances and future perspectives. Eur J Med Chem. 2023 May 5;253:115326. doi: 10.1016/j.ejmech.2023.115326. Epub 2023 Mar 31. PMID: 37023679.