Enmetazobactam HI

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MedKoo CAT#: 124798

CAS#: 1379594-98-5 (HI)

Description: Enmetazobactam, also known as AAI-101, is a novel β-lactam/β-lactamase inhibitor. AAI101 is similar in structure to tazobactam, with one important difference. AAI101 possesses a strategically placed methyl group that gives the inhibitor a net neutral charge, enhancing bacterial cell penetration. AAI101 paired with cefepime, also a zwitterion, was approved for the treatment of serious Gram-negative infections. AAI101 was found to restore the activity of cefepime against class A ESBLs (e.g., CTX-M-15) and demonstrated increased potency compared to that of piperacillin-tazobactam when tested against an established isogenic panel.

Chemical Structure

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Enmetazobactam HI
CAS# 1379594-98-5 (HI)
Instruction

Theoretical Analysis

MedKoo Cat#: 124798
Name: Enmetazobactam HI
CAS#: 1379594-98-5 (HI)
Chemical Formula: C11H15IN4O5S
Exact Mass: 441.98
Molecular Weight: 442.230
Elemental Analysis: C, 29.88; H, 3.42; I, 28.70; N, 12.67; O, 18.09; S, 7.25

Price and Availability

This product is not in stock, which may be available by custom synthesis. For cost-effective reason, minimum order is 1g (price is usually high, lead time is 2~3 months, depending on the technical challenge). Quote less than 1g will not be provided. To request quote, please email to sales @medkoo.com or click below button.
Note: Price will be listed if it is available in the future.

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Related CAS #: 1001404-83-6 (free form)   1379594-98-5 (HI)    

Synonym: Enmetazobactam hydriodide; AAI-101; AAI-101; AAI-101,

IUPAC/Chemical Name: 1-(((2S,3S,5R)-2-carboxy-3-methyl-4,4-dioxido-7-oxo-4-thia-1-azabicyclo[3.2.0]heptan-3-yl)methyl)-3-methyl-1H-1,2,3-triazol-3-ium iodide

InChi Key: GSBNEXCMKCGSGW-GNPQZNTHSA-N

InChi Code: InChI=1S/C11H14N4O5S.HI/c1-11(6-14-4-3-13(2)12-14)9(10(17)18)15-7(16)5-8(15)21(11,19)20;/h3-4,8-9H,5-6H2,1-2H3;1H/t8-,9+,11+;/m1./s1

SMILES Code: [I-].[H][C@@]12CC(=O)N1[C@@H](C(O)=O)[C@](C)(CN3C=C[N+](C)=N3)S2(=O)=O

Appearance: To be determined

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: To be determined

Shelf Life: >2 years if stored properly

Drug Formulation: To be determined

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: The enzymological properties of AAI101 further revealed that AAI101 possessed a unique mechanism of β-lactamase inhibition compared to that of tazobactam. Additionally, upon reaction with AAI101, CTX-M-15 was modified to an inactive state. Notably, the in vivo efficacy of cefepime-AAI101 was demonstrated using a mouse septicemia model, indicating the ability of AAI101 to bolster significantly the therapeutic efficacy of cefepime in vivo The combination of AAI101 with cefepime represents a potential carbapenem-sparing treatment regimen for infections suspected to be caused by Enterobacteriaceae expressing ESBLs.

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 442.23 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.

Recalculate based on batch purity %
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:
In vitro protocol:
In vivo protocol:

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1: Bassetti M, Castaldo N, Fantin A, Giacobbe DR, Vena A. Antibiotic therapy for nonfermenting Gram-negative bacilli infections: future perspectives. Curr Opin Infect Dis. 2023 Dec 1;36(6):615-622. doi: 10.1097/QCO.0000000000000984. Epub 2023 Oct 16. PMID: 37846592.


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6: Hsu CK, Tsai WW, Lai CC. Cefepime/Enmetazobactam vs Piperacillin/Tazobactam and Complicated Urinary Tract Infection or Acute Pyelonephritis. JAMA. 2023 Feb 28;329(8):684-685. doi: 10.1001/jama.2022.22870. PMID: 36853255.


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8: Maki DG. In complicated UTI or pyelonephritis, cefepime-enmetazobactam increased success vs. piperacillin-tazobactam at 14 d. Ann Intern Med. 2023 Feb;176(2):JC21. doi: 10.7326/J22-0114. Epub 2023 Feb 7. PMID: 36745895.


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11: Kadry AA, El-Antrawy MA, El-Ganiny AM. Management of clinical infections of Escherichia coli by new β-lactam/β-lactamase inhibitor combinations. Iran J Microbiol. 2022 Aug;14(4):466-474. doi: 10.18502/ijm.v14i4.10232. PMID: 36721515; PMCID: PMC9867644.


12: Nussbaumer-Pröll A, Eberl S, Belley A, Knechtle P, Huband MD, Huynh HK, Zeitlinger M. Impact of surfactants and other body fluids on in vitro activity of a novel β-lactamase inhibitor enmetazobactam in combination with cefepime against clinical isolates of Klebsiella pneumoniae. J Antibiot (Tokyo). 2023 Mar;76(3):183-189. doi: 10.1038/s41429-022-00592-w. Epub 2023 Jan 23. PMID: 36690707.


13: Advani SD, Claeys K. Cefepime/Enmetazobactam for Complicated Urinary Tract Infections. JAMA. 2022 Oct 4;328(13):1299-1301. doi: 10.1001/jama.2022.15228. PMID: 36194235.


14: Kaye KS, Belley A, Barth P, Lahlou O, Knechtle P, Motta P, Velicitat P. Effect of Cefepime/Enmetazobactam vs Piperacillin/Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis: A Randomized Clinical Trial. JAMA. 2022 Oct 4;328(13):1304-1314. doi: 10.1001/jama.2022.17034. PMID: 36194218; PMCID: PMC9533186.


15: Hinchliffe P, Tooke CL, Bethel CR, Wang B, Arthur C, Heesom KJ, Shapiro S, Schlatzer DM, Papp-Wallace KM, Bonomo RA, Spencer J. Penicillanic Acid Sulfones Inactivate the Extended-Spectrum β-Lactamase CTX-M-15 through Formation of a Serine-Lysine Cross-Link: an Alternative Mechanism of β-Lactamase Inhibition. mBio. 2022 Jun 28;13(3):e0179321. doi: 10.1128/mbio.01793-21. Epub 2022 May 25. PMID: 35612361; PMCID: PMC9239225.


16: Lang PA, Raj R, Tumber A, Lohans CT, Rabe P, Robinson CV, Brem J, Schofield CJ. Studies on enmetazobactam clarify mechanisms of widely used β-lactamase inhibitors. Proc Natl Acad Sci U S A. 2022 May 3;119(18):e2117310119. doi: 10.1073/pnas.2117310119. Epub 2022 Apr 29. PMID: 35486701; PMCID: PMC9170034.


17: Shapiro S. Cefepime/Enmetazobactam Is a Clinically Effective Combination Targeting Extended-Spectrum β-Lactamase-Producing Enterobacterales. Antimicrob Agents Chemother. 2022 May 17;66(5):e0029822. doi: 10.1128/aac.00298-22. Epub 2022 Apr 26. PMID: 35471043; PMCID: PMC9112890.


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20: Saral Sariyer A. Three new inhibitors of class A β-lactamases evaluated by molecular docking and dynamics simulations methods: relebactam, enmetazobactam, and QPX7728. J Mol Model. 2022 Mar 4;28(4):76. doi: 10.1007/s00894-022-05073-3. PMID: 35243556.