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Chemistry

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Also known as: 1360457-46-0, Rpx7009, Rpx-7009, Vaborbactam [inn], Chembl3317857, 2-[(3r,6s)-2-hydroxy-3-[(2-thiophen-2-ylacetyl)amino]oxaborinan-6-yl]acetic acid
Molecular Formula
C12H16BNO5S
Molecular Weight
297.14  g/mol
InChI Key
IOOWNWLVCOUUEX-WPRPVWTQSA-N
FDA UNII
1C75676F8V

Vaborbactam
Vaborbactam is a -lactamase inhibitor based on a cyclic boronic acid pharmacophore. It has been used in trials investigating the treatment of bacterial infections in subjects with varying degrees of renal insufficiency. In August 2017, a combination antibacterial therapy under the market name Vabomere was approved by the FDA for the treatment of adult patients with complicated urinary tract infections (cUTI). Vabomere consists of vaborbactam and [Meropenem] for intravenous administration. Vaborbactam is added to the therapy to reduce the extent meropenem degradation by inhibiting the serine beta-lactamases expressed by the microorganism of target. The treatment aims to resolve infection-related symptoms of cUTI and achieve negative urine culture, when the infections are proven or strongly suspected to be caused by susceptible bacteria.
Vaborbactam is a beta Lactamase Inhibitor. The mechanism of action of vaborbactam is as a beta Lactamase Inhibitor.
1 2D Structure

Vaborbactam

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
2-[(3R,6S)-2-hydroxy-3-[(2-thiophen-2-ylacetyl)amino]oxaborinan-6-yl]acetic acid
2.1.2 InChI
InChI=1S/C12H16BNO5S/c15-11(7-9-2-1-5-20-9)14-10-4-3-8(6-12(16)17)19-13(10)18/h1-2,5,8,10,18H,3-4,6-7H2,(H,14,15)(H,16,17)/t8-,10-/m0/s1
2.1.3 InChI Key
IOOWNWLVCOUUEX-WPRPVWTQSA-N
2.1.4 Canonical SMILES
B1(C(CCC(O1)CC(=O)O)NC(=O)CC2=CC=CS2)O
2.1.5 Isomeric SMILES
B1([C@H](CC[C@H](O1)CC(=O)O)NC(=O)CC2=CC=CS2)O
2.2 Other Identifiers
2.2.1 UNII
1C75676F8V
2.3 Synonyms
2.3.1 Depositor-Supplied Synonyms

1. 1360457-46-0

2. Rpx7009

3. Rpx-7009

4. Vaborbactam [inn]

5. Chembl3317857

6. 2-[(3r,6s)-2-hydroxy-3-[(2-thiophen-2-ylacetyl)amino]oxaborinan-6-yl]acetic Acid

7. 1c75676f8v

8. 1,2-oxaborinane-6-acetic Acid, 2-hydroxy-3-((2-(2-thienyl)acetyl)amino)-, (3r,6s)-

9. 2-((3r,6s)-2-hydroxy-3-(2-(thiophen-2-yl)acetamido)-1,2-oxaborinan-6-yl)acetic Acid

10. Rpx 7009

11. Unii-1c75676f8v

12. Vaborbactam [mi]

13. Vaborbactam. Rpx7009

14. Vaborbactam (usan/inn)

15. Vaborbactam [usan:inn]

16. Vaborbactam [usan]

17. Vaborbactam [who-dd]

18. Schembl620289

19. Gtpl10871

20. Vaborbactam [orange Book]

21. Dtxsid901027690

22. Vabomere (vaborbactam + Meropenem)

23. Ex-a2589

24. Bdbm50089084

25. Mfcd28502176

26. Vabomere Component Vaborbactam

27. Akos032961376

28. Carbavance Component Vaborbactam

29. Cs-6445

30. Db12107

31. Compound 9f [pmid: 25782055]

32. Ncgc00510003-01

33. (3r,6s)-

34. 1575712-03-6

35. Bv163750

36. Hy-19930

37. Vaborbactam Component Of Carbavance

38. 2-hydroxy-3-((2-(2-thienyl)acetyl)amino)-

39. D10998

40. Q27252228

41. {(3r,6s)-2-hydroxy-3-[(thiophen-2-ylacetyl)amino]-1,2-oxaborinan-6-yl}acetic Acid; 2-((3r,6s)-2-hydroxy-3-(2-(thiophen-2-yl)acetamido)-1,2-oxaborinan-6-yl)acetic Acid; 2-[(3r,6s)-2-hydroxy-3-[(2-thiophen-2-ylacetyl)amino]oxaborinan-6-yl]acetic Acid; 1,2-oxaborinane-6-acetic Acid

2.4 Create Date
2012-03-05
3 Chemical and Physical Properties
Molecular Weight 297.14 g/mol
Molecular Formula C12H16BNO5S
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count6
Rotatable Bond Count5
Exact Mass297.0842240 g/mol
Monoisotopic Mass297.0842240 g/mol
Topological Polar Surface Area124 Ų
Heavy Atom Count20
Formal Charge0
Complexity370
Isotope Atom Count0
Defined Atom Stereocenter Count2
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Indication

Indicated in combination with meropenem for the treatment of patients 18 years of age and older with complicated urinary tract infections (cUTI) including pyelonephritis caused by the following susceptible microorganisms: _Escherichia coli_, _Klebsiella pneumoniae_, and _Enterobacter cloacae_ species complex.


FDA Label


Treatment of Gram-negative bacterial infections


5 Pharmacology and Biochemistry
5.1 Pharmacology

Vaborbactam shows no antibacterial activity alone; it serves to restore the antibacterial activity of other antibacterial agents such as meropenem by attenuating their degradation by inhibiting certain serine beta-lactamases of microorganisms. Vaborbactam does not decrease the activity of meropenem against meropenem-susceptible organisms. Vaborbactam in combination with meropenem, which is a penem antibacterial drug, potentiates the bactericidal actions of meropenem against carbapenem-resistant KPC-containing _Escherichia coli_, _Klebsiella pneumoniae_, and _Enterobacter cloacae_ in a concentration-dependent manner. It restored the antimicrobial activity of meropenem in animal models of infection caused by some meropenem non-susceptible KPC-producing Enterobacteriaceae.


5.2 MeSH Pharmacological Classification

Anti-Bacterial Agents

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)


beta-Lactamase Inhibitors

Endogenous substances and drugs that inhibit or block the activity of BETA-LACTAMASES. (See all compounds classified as beta-Lactamase Inhibitors.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
VABORBACTAM
5.3.2 FDA UNII
1C75676F8V
5.3.3 Pharmacological Classes
Mechanisms of Action [MoA] - beta Lactamase Inhibitors
5.4 Absorption, Distribution and Excretion

Absorption

The peak plasma concentrations (Cmax) and AUC of vaborbactam increase in a dose-proportional manner. In healthy adult subjects, the Cmax following administration of multiple 2 g dose as a 3-hour infusion was 55.6 mg/L and AUC was 588 mgh/L. In patients with the same dosing regimen, the Cmax was 71.3 mg/L and AUC was 835 mgh/L at steady state. The exposure of vaborbactam in terms of Cmax and AUC are not expected to change with repeated dosing, and there was no evidence of accumulation of vaborbactam in plasma in a repeated dosing study.


Route of Elimination

Vaborbactam predominantly undergoes renal excretion, where about 75 to 95% of the dose is excreted unchanged in the urine over a 24 to 48 hour period.


Volume of Distribution

The steady-state volume of distribution of vaborbactam in patients was 18.6 L.


Clearance

The mean renal clearance for vaborbactam was 8.9 L/h. The mean non-renal clearance for vaborbactam was 2.0 L/h indicating nearly complete elimination of vaborbactam by the renal route. The clearance of vaborbactam in healthy subjects following administration of multiple doses of 2 g as a 3-hour infusion was 10.9 L/h. The clearance of vaborbactam in patients following administration of 2 g by 3 hour infusion was 7.95 L/h.


5.5 Metabolism/Metabolites

Vaborbactam does not undergo metabolism.


5.6 Biological Half-Life

The half life of vaborbactam in healthy subjects following multiple 2 g dose administration as a 3-hour infusion was 1.68 hours. The half life of vaborbactam following administration of 2 g by 3 hour infusion was 2.25 hours.


5.7 Mechanism of Action

Vaborbactam is a cyclic boronic acid pharmacophore -lactamase inhibitor that elicits potent inhibition of _Klebsiella pneumoniae_ carbapenemase (KPC) enzymes and other Ambler class A and C enzymes such as serine -lactamases that confer resistance to commonly-used antibiotics such as Carbapenems. Vaborbactam is a potent inhibitor of class A carbapenemases, such as KPC, as well as an inhibitor of other class A (CTX-M, SHV, TEM) and class C (P99, MIR, FOX) beta-lactamases. Vaborbactam interacts with -lactamases of Ambler classes A and C via precovalent and covalent binding. It exerts no inhibitory actions on class D or class B carbapenemases. The production of contemporary -lactamase by bacterial isolates potentiate the degradation of -lactam antibiotic agents, rendering them clinically ineffective and posing challenges for patients receiving the standard antibiotic therapy. In combination with meropenem, varborbactam acts as a non-suicidal beta-lactamase inhibitor that protects meropenem from degradation mediated by serine beta-lactamases such as _Klebsiella pneumoniae_ carbapenemase (KPC).


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ABOUT THIS PAGE

Vaborbactam Manufacturers

A Vaborbactam manufacturer is defined as any person or entity involved in the manufacture, preparation, processing, compounding or propagation of Vaborbactam, including repackagers and relabelers. The FDA regulates Vaborbactam manufacturers to ensure that their products comply with relevant laws and regulations and are safe and effective to use. Vaborbactam API Manufacturers are required to adhere to Good Manufacturing Practices (GMP) to ensure that their products are consistently manufactured to meet established quality criteria.

click here to find a list of Vaborbactam manufacturers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PhamaCompass.

Vaborbactam Suppliers

A Vaborbactam supplier is an individual or a company that provides Vaborbactam active pharmaceutical ingredient (API) or Vaborbactam finished formulations upon request. The Vaborbactam suppliers may include Vaborbactam API manufacturers, exporters, distributors and traders.

click here to find a list of Vaborbactam suppliers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PharmaCompass.

Vaborbactam GMP

Vaborbactam Active pharmaceutical ingredient (API) is produced in GMP-certified manufacturing facility.

GMP stands for Good Manufacturing Practices, which is a system used in the pharmaceutical industry to make sure that goods are regularly produced and monitored in accordance with quality standards. The FDA’s current Good Manufacturing Practices requirements are referred to as cGMP or current GMP which indicates that the company follows the most recent GMP specifications. The World Health Organization (WHO) has its own set of GMP guidelines, called the WHO GMP. Different countries can also set their own guidelines for GMP like China (Chinese GMP) or the EU (EU GMP).

PharmaCompass offers a list of Vaborbactam GMP manufacturers, exporters & distributors, which can be sorted by USDMF, JDMF, KDMF, CEP (COS), WC, API price, and more, enabling you to easily find the right Vaborbactam GMP manufacturer or Vaborbactam GMP API supplier for your needs.

Vaborbactam CoA

A Vaborbactam CoA (Certificate of Analysis) is a formal document that attests to Vaborbactam's compliance with Vaborbactam specifications and serves as a tool for batch-level quality control.

Vaborbactam CoA mostly includes findings from lab analyses of a specific batch. For each Vaborbactam CoA document that a company creates, the USFDA specifies specific requirements, such as supplier information, material identification, transportation data, evidence of conformity and signature data.

Vaborbactam may be tested according to a variety of international standards, such as European Pharmacopoeia (Vaborbactam EP), Vaborbactam JP (Japanese Pharmacopeia) and the US Pharmacopoeia (Vaborbactam USP).

Inform the supplier about your product requirements, specifying if you need a product with particular monograph like EP (Ph. Eur.), USP, JP, BP, or any other quality. In addition, clarify whether you need hydrochloride (HCl), anhydricum, base, micronisatum or a specific level of purity. To find reputable suppliers, utilize the filters and select those certified by GMP, FDA, or any other certification as per your requirement.
For your convenience, we have listed synonyms and CAS numbers to help you find the best supplier. The use of synonyms and CAS numbers can be helpful in identifying potential suppliers, but it is crucial to note that they might not always indicate the exact same product. It is important to confirm the product details with the supplier before making a purchase to ensure that it meets your requirements.
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