Taniborbactam
(Synonyms: VNRX-5133) 目录号 : GC32353
Taniborbactam是一种有效的β-lactamase抑制剂，对β-lactamase不同亚型SHV-5，KPC-2，VIM-2和AmpC的IC50值<100nM，对OXA-1的IC50值为0.1-1μM，可用于细菌感染的研究。
Cas No.:1613267-49-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Taniborbactam is a potent inhibitor of β-lactamase, with IC50s of <100 nM for SHV-5, KPC-2, VIM-2, and AmpC β-lactamase, and 0.1 to 1 μM for OXA-1 β-lactamase, used in the research of bacterial infections[1].
Taniborbactam (Example 15) is a potent inhibitor of β-lactamase, with IC50s of <100 nM for SHV-5, KPC-2, VIM-2, and AmpC β-lactamase, and 0.1 to 1 μM for OXA-1 β-lactamase, used in the research of bacterial infections[1].
[1]. Christopher J. Burns, et al. Beta-lactamase inhibitors. WO2014089365A1
| Cas No. | 1613267-49-4 | SDF | |
| 别名 | VNRX-5133 | ||
| Canonical SMILES | OC(C1=C(OB(O)[C@@H](NC(C[C@@H]2CC[C@@H](NCCN)CC2)=O)C3)C3=CC=C1)=O | ||
| 分子式 | C19H28BN3O5 | 分子量 | 389.25 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.569 mL | 12.8452 mL | 25.6904 mL |
| 5 mM | 0.5138 mL | 2.569 mL | 5.1381 mL |
| 10 mM | 0.2569 mL | 1.2845 mL | 2.569 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Activity of cefiderocol, imipenem/relebactam, cefepime/Taniborbactam and cefepime/zidebactam against ceftolozane/tazobactam- and ceftazidime/avibactam-resistant Pseudomonas aeruginosa
J Antimicrob Chemother 2022 Sep 30;77(10):2809-2815.PMID:35904000DOI:10.1093/jac/dkac241.
Objectives: To evaluate the activity of cefiderocol, imipenem/relebactam, cefepime/Taniborbactam and cefepime/zidebactam against a clinical and laboratory collection of ceftolozane/tazobactam- and ceftazidime/avibactam-resistant Pseudomonas aeruginosa 尾-lactamase mutants. Methods: The activity of cefiderocol, imipenem/relebactam, cefepime/Taniborbactam, cefepime/zidebactam and comparators was evaluated against a collection of 30 molecularly characterized ceftolozane/tazobactam- and/or ceftazidime/avibactam-resistant P. aeruginosa isolates from patients previously treated with cephalosporins. To evaluate how the different 尾-lactamases in the clinical isolates affected the resistance to these agents, a copy of each blaPDC, blaOXA-2 and blaOXA-10 ancestral and mutant allele from the clinical isolates was cloned in pUCp24 and expressed in dual blaPDC-oprD (for blaPDC-like genes) or single oprD (for blaOXA-2-like and blaOXA-10-like genes) PAO1 knockout mutants. MICs were determined using reference methodologies. Results: For all isolates, MICs were higher than 4 and/or 8 mg/L for ceftolozane/tazobactam and ceftazidime/avibactam, respectively. Cefiderocol was the most active agent, showing activity against all isolates, except one clinical isolate that carried an R504C substitution in PBP3 (MIC = 16 mg/L). Imipenem/relebactam was highly active against all isolates, except two clinical isolates that carried the VIM-20 carbapenemase. Cefepime/zidebactam and cefepime/Taniborbactam displayed activity against most of the isolates, but resistance was observed in some strains with PBP3 amino acid substitutions or that overexpressed mexAB-oprM or mexXY efflux pumps. Evaluation of transformants revealed that OXA-2 and OXA-10 extended-spectrum variants cause a 2-fold increase in the MIC of cefiderocol relative to parental enzymes. Conclusions: Cefiderocol, imipenem/relebactam, cefepime/Taniborbactam and cefepime/zidebactam show promising and complementary in vitro activity against ceftolozane/tazobactam- and ceftazidime/avibactam-resistant P. aeruginosa. These agents may represent potential therapeutic options for ceftolozane/tazobactam- and ceftazidime/avibactam-resistant P. aeruginosa infections.
Activity of 尾-lactam/Taniborbactam (VNRX-5133) combinations against carbapenem-resistant Gram-negative bacteria
J Antimicrob Chemother 2021 Jan 1;76(1):160-170.PMID:33305800DOI:10.1093/jac/dkaa391.
Background: Boronates are of growing interest as 尾-lactamase inhibitors. The only marketed analogue, vaborbactam, principally targets KPC carbapenemases, but Taniborbactam (VNRX-5133, Venatorx) has a broader spectrum. Methods: MICs of cefepime and meropenem were determined combined with Taniborbactam or avibactam for carbapenem-resistant UK isolates. 尾-Lactamase genes and porin alterations were sought by PCR or sequencing. Results: Taniborbactam potentiated partner 尾-lactams against: (i) Enterobacterales with KPC, other class A, OXA-48-like, VIM and NDM (not IMP) carbapenemases; and (ii) Enterobacterales inferred to have combinations of ESBL or AmpC activity and impermeability. Potentiation of cefepime (the partner for clinical development) by Taniborbactam was slightly weaker than by avibactam for Enterobacterales with KPC or OXA-48-like carbapenemases, but MICs of cefepime/Taniborbactam were similar to those of ceftazidime/avibactam, and the spectrum was wider. MICs of cefepime/Taniborbactam nonetheless remained >8 + 4 mg/L for 22%-32% of NDM-producing Enterobacterales. Correlates of raised cefepime/Taniborbactam MICs among these NDM Enterobacterales were a cefepime MIC >128 mg/L, particular STs and, for Escherichia coli only: (i) the particular blaNDM variant (even though published data suggest all variants are inhibited similarly); (ii) inserts in PBP3; and (iii) raised aztreonam/avibactam MICs. Little or no potentiation of cefepime or meropenem was seen for Pseudomonas aeruginosa and Acinetobacter baumannii with MBLs, probably reflecting slower uptake or stronger efflux. Potentiation of cefepime was seen for Stenotrophomonas maltophilia and Elizabethkingia meningoseptica, which have both chromosomal ESBLs and MBLs. Conclusions: Taniborbactam broadly reversed cefepime or meropenem non-susceptibility in Enterobacterales and, less reliably, in non-fermenters.
Safety and Pharmacokinetics of Taniborbactam (VNRX-5133) with Cefepime in Subjects with Various Degrees of Renal Impairment
Antimicrob Agents Chemother 2022 Sep 20;66(9):e0025322.PMID:35920662DOI:10.1128/aac.00253-22.
Taniborbactam, an investigational 尾-lactamase inhibitor that is active against both serine- and metallo-尾-lactamases, is being developed in combination with cefepime to treat serious infections caused by multidrug-resistant Gram-negative bacteria. Anticipating the use of cefepime-taniborbactam in patients with impaired renal function, an open-label, single-dose clinical study was performed to examine the pharmacokinetics of both drugs in subjects with various degrees of renal function. Hemodialysis-dependent subjects were also studied to examine the amounts of cefepime and Taniborbactam dialyzed. Single intravenous infusions of 2 g cefepime and 0.5 g Taniborbactam coadministered over 2 h were examined, with hemodialysis-dependent subjects receiving doses both on- and off-dialysis. No subjects experienced serious adverse events or discontinued treatment due to adverse events. The majority of adverse events observed were mild in severity, and there were no trends in the safety of cefepime-taniborbactam related to declining renal function or the timing of hemodialysis. Clinically significant and similar decreases in drug clearance with declining renal function were observed for both cefepime and Taniborbactam. The respective decreases in geometric mean clearance for subjects with mild, moderate, and severe renal impairment compared to subjects with normal renal function were 18%, 63%, and 78% for cefepime and 15%, 63%, and 81% for Taniborbactam, respectively. Decreases in clearance were similar for both drugs and were shown to be proportional to decreases in renal function. Both cefepime and Taniborbactam were dialyzable, with similar amounts removed during 4 h of hemodialysis. This study is registered at ClinicalTrials.gov as NCT03690362.
Activity of cefepime/Taniborbactam and comparators against whole genome sequenced ertapenem-non-susceptible Enterobacterales clinical isolates: CANWARD 2007-19
JAC Antimicrob Resist 2022 Feb 7;4(1):dlab197.PMID:35156028DOI:10.1093/jacamr/dlab197.
Objectives: This study assessed in vitro activities of cefepime/Taniborbactam and comparator antimicrobial agents against ertapenem-non-susceptible Enterobacterales (ENSE) clinical isolates collected from the CANWARD study 2007-19, and associations between MIC and various mechanisms of 尾-lactam resistance identified using WGS. Methods: A total of 179 ENSE (MIC 鈮?1 mg/L) isolates underwent susceptibility testing using reference CLSI broth microdilution. WGS was performed using the Illumina NextSeq platform. Carbapenemases, ESBLs and other 尾-lactamases were identified using ResFinder 4.0. Alterations in ompC/F and ftsI (PBP3) were identified by comparing extracted sequences to the appropriate NCBI reference gene. Porin alterations were analysed with Provean v1.1.3. Specific alterations of interest in PBP3 included a YRIN or YRIK insertion after P333. Results: Cefepime/Taniborbactam was highly active (MIC50/MIC90, 0.5/2 mg/L; 177/179 isolates inhibited at 鈮?8 mg/L) against ENSE with various antimicrobial resistance phenotypes. Thirteen (7.3%) of the 179 ENSE isolates demonstrated cefepime/Taniborbactam MIC values 鈮?4 mg/L and possessed combinations of 尾-lactam resistance mechanisms, including a carbapenemase and/or ESBL and/or other 尾-lactamase genes, as well as alterations in OmpC and/or OmpF and/or PBP3. Of the two Escherichia coli isolates that demonstrated a cefepime/Taniborbactam MIC of 32 mg/L, one possessed NDM-5, OXA-181 and TEM-1B, an OmpC alteration and P333_Y334insYRIN in PBP3, while the second contained CTX-M-71, a truncated OmpF and a large alteration in OmpC (F182_R195delinsMTTNGRDDVFE). Conclusions: Cefepime/Taniborbactam was highly active against ENSE with various antimicrobial resistance phenotypes/genotypes. ENSE isolates with cefepime/Taniborbactam MIC values 鈮?4 mg/L possessed combinations of 尾-lactam resistance mechanisms, including 尾-lactamase genes, as well as alterations in OmpC and/or OmpF and/or PBP3.
Clinical exposure-response relationship of cefepime/Taniborbactam against Gram-negative organisms in the murine complicated urinary tract infection model
J Antimicrob Chemother 2022 Feb 2;77(2):443-447.PMID:34747449DOI:10.1093/jac/dkab405.
Objectives: Complicated urinary tract infections (cUTIs) are frequently encountered in hospitals and ICUs. Increasingly, the causative pathogens harbour enzymatic resistance mechanisms. Taniborbactam is a novel 尾-lactamase inhibitor with activity against Ambler class A, B, C and D 尾-lactamases. Herein, we assessed the efficacy of cefepime alone and the combination cefepime/Taniborbactam in a neutropenic murine cUTI model. Methods: Eighteen cefepime-resistant clinical isolates (9 Enterobacterales, 3 Pseudomonas aeruginosa and 6 Stenotrophomonas maltophilia; cefepime MIC = 32 to >512 mg/L) were assessed. Cefepime/Taniborbactam MICs ranged from 0.06 to 128 mg/L. Human-simulated plasma regimens (HSRs) of cefepime alone and in combination with Taniborbactam were developed in the murine cUTI model. The efficacy of cefepime HSR and cefepime/Taniborbactam HSR was determined as the change in log10 cfu/kidney at 48 h compared with 48 h controls. Results: Mean 卤 SD initial bacterial burden was 5.66 卤 0.56 log10 cfu/kidney, which increased to 9.05 卤 0.39 log10 cfu/kidney at 48 h. The cefepime HSR was ineffective, as bacterial burden was similar to untreated controls (-0.14 卤 0.40 change in log10 cfu/kidney). In contrast, cefepime/Taniborbactam exhibited substantial killing, with log10 cfu/kidney changes of -5.48 卤 1.3, -4.79 卤 0.3 and -5.04 卤 0.7 for ESBL/AmpC-, KPC- and OXA-48-harbouring Enterobacterales, respectively. Cefepime/Taniborbactam also exhibited robust killing of P. aeruginosa (-6.5 卤 0.26) and S. maltophilia (-5.66 卤 0.71). Conclusions: Humanized exposures of cefepime/Taniborbactam achieved robust killing of Enterobacterales, P. aeruginosa and S. maltophilia harbouring ESBL, AmpC, KPC and/or OXA-48. These data support the role of cefepime/Taniborbactam for cUTI treatment for cefepime/Taniborbactam MICs up to 32 mg/L.