Enmetazobactam HI | CAS#1379594-98-5 | ESBL inhibitor

MedKoo Cat#: 124798 | Name: Enmetazobactam HI

Description:

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

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

Enmetazobactam HI

CAS#1379594-98-5 (HI)

Theoretical Analysis

MedKoo Cat#: 124798

Name: Enmetazobactam HI

CAS#: 1379594-98-5 (HI)

Chemical Formula: C11H15IN4O5S

Exact Mass: 441.9800

Molecular Weight: 442.23

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 currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.

Bulk Inquiry

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.

Instruction

View handling instruction

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.

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

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PMID: 37107124; PMCID: PMC10135111. 4: Hung KC, Tsai WW, Hsu CW, Lai CC, Tang HJ, Chen IW. Clinical efficacy and safety of novel antibiotics for complicated urinary tract infection: A systematic review and meta-analysis of randomized controlled trials. Int J Antimicrob Agents. 2023 Jul;62(1):106830. doi: 10.1016/j.ijantimicag.2023.106830. Epub 2023 Apr 24. PMID: 37100354. 5: Severance ZC, Nuñez JI, Le-McClain AT, Malinky CA, Bensen RC, Fogle RS, Manginelli GW, Sakers SH, Falcon EC, Bui RH, Snead KJ, Bourne CR, Burgett AWG. Structure-Activity Relationships of Ligand Binding to Oxysterol-Binding Protein (OSBP) and OSBP-Related Protein 4. J Med Chem. 2023 Mar 23;66(6):3866-3875. doi: 10.1021/acs.jmedchem.2c01025. Epub 2023 Mar 14. PMID: 36916802; PMCID: PMC10786236. 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. 7: Kaye KS, Belley A, Velicitat P. Cefepime/Enmetazobactam vs Piperacillin/Tazobactam and Complicated Urinary Tract Infection or Acute Pyelonephritis-Reply. JAMA. 2023 Feb 28;329(8):685. doi: 10.1001/jama.2022.22873. PMID: 36853252. 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. 9: Vázquez-Ucha JC, Alonso-Garcia I, Guijarro-Sánchez P, Lasarte-Monterrubio C, Álvarez-Fraga L, Cendón-Esteve A, Outeda M, Maceiras R, Peña-Escolano A, Martínez-Guitián M, Arca-Suárez J, Bou G, Beceiro A; GEMARA-SEIMC/REIPI Enterobacterales Study Group. Activity of aztreonam in combination with novel β-lactamase inhibitors against metallo-β-lactamase-producing Enterobacterales from Spain. Int J Antimicrob Agents. 2023 Apr;61(4):106738. doi: 10.1016/j.ijantimicag.2023.106738. Epub 2023 Feb 3. PMID: 36736925. 10: Kadry AA, El-Antrawy MA, El-Ganiny AM. Impact of short chain fatty acids (SCFAs) on antimicrobial activity of new β-lactam/β-lactamase inhibitor combinations and on virulence of Escherichia coli isolates. J Antibiot (Tokyo). 2023 Apr;76(4):225-235. doi: 10.1038/s41429-023-00595-1. Epub 2023 Feb 1. PMID: 36726014; PMCID: PMC10040337. 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. 18: Vázquez-Ucha JC, Lasarte-Monterrubio C, Guijarro-Sánchez P, Oviaño M, Álvarez-Fraga L, Alonso-García I, Arca-Suárez J, Bou G, Beceiro A. Reply to Shapiro, "Cefepime/Enmetazobactam Is a Clinically Effective Combination Targeting Extended-Spectrum β-Lactamase-Producing Enterobacterales". Antimicrob Agents Chemother. 2022 May 17;66(5):e0035322. doi: 10.1128/aac.00353-22. Epub 2022 Apr 26. PMID: 35471039; PMCID: PMC9112983. 19: Principe L, Lupia T, Andriani L, Campanile F, Carcione D, Corcione S, De Rosa FG, Luzzati R, Stroffolini G, Steyde M, Decorti G, Di Bella S. Microbiological, Clinical, and PK/PD Features of the New Anti-Gram-Negative Antibiotics: β-Lactam/β-Lactamase Inhibitors in Combination and Cefiderocol-An All-Inclusive Guide for Clinicians. Pharmaceuticals (Basel). 2022 Apr 12;15(4):463. doi: 10.3390/ph15040463. PMID: 35455461; PMCID: PMC9028825. 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.