Target Information
Target General Information | Top | |||||
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Target ID |
T38179
(Former ID: TTDS00228)
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Target Name |
Staphylococcus Beta-lactamase (Stap-coc blaZ)
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Synonyms |
blaZ; Cephalosporinase
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Gene Name |
Stap-coc blaZ
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 3 Target-related Diseases | + | ||||
1 | Bacterial infection [ICD-11: 1A00-1C4Z] | |||||
2 | Infectious gastroenteritis/colitis [ICD-11: 1A40] | |||||
3 | Urinary tract infection [ICD-11: GC08] | |||||
Function |
This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
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BioChemical Class |
Carbon-nitrogen hydrolase
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UniProt ID | ||||||
EC Number |
EC 3.5.2.6
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Sequence |
MKKLIFLIVIALVLSACNSNSSHAKELNDLEKKYNAHIGVYALDTKSGKEVKFNSDKRFA
YASTSKAINSAILLEQVPYNKLNKKVHINKDDIVAYSPILEKYVGKDITLKALIEASMTY SDNTANNKIIKEIGGIKKVKQRLKELGDKVTNPVRYEIELNYYSPKSKKDTSTPAAFGKT LNKLIANGKLSKENKKFLLDLMLNNKSGDTLIKDGVPKDYKVADKSGQAITYASRNDVAF VYPKGQSEPIVLVIFTNKDNKSDKPNDKLISETAKSVMKEF Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 4 Approved Drugs | + | ||||
1 | Ceftolozane/tazobactam | Drug Info | Approved | Discovery agent | [2] | |
2 | Clavulanate | Drug Info | Approved | Bacterial infection | [3] | |
3 | Meropenem + vaborbactam | Drug Info | Approved | Urinary tract infection | [4] | |
4 | Tazobactam | Drug Info | Approved | Bacterial infection | [5] | |
Clinical Trial Drug(s) | [+] 13 Clinical Trial Drugs | + | ||||
1 | CAZ AVI | Drug Info | Phase 3 | Serious infection | [6] | |
2 | Enmetazobactam | Drug Info | Phase 3 | Urinary tract infection | [7] | |
3 | Vaborbactam | Drug Info | Phase 3 | Urinary tract infection | [8] | |
4 | CXL | Drug Info | Phase 2 | Methicillin-resistant staphylococci infection | [9] | |
5 | MK-7655 | Drug Info | Phase 2 | Bacterial infection | [10] | |
6 | ETX0282 | Drug Info | Phase 1 | Urinary tract infection | [11] | |
7 | ME-1071 | Drug Info | Phase 1 | Bacterial infection | [12] | |
8 | OP-0595 | Drug Info | Phase 1 | Bacterial infection | [13] | |
9 | QPX7728 | Drug Info | Phase 1 | Bacterial infection | [14] | |
10 | QPX7831 | Drug Info | Phase 1 | Gram-negative bacterial infection | [15] | |
11 | RASV-Sp | Drug Info | Phase 1 | Streptococcus infection | [16] | |
12 | VNRX-5133 | Drug Info | Phase 1 | Bacterial infection | [17] | |
13 | XNW4107 | Drug Info | Phase 1 | Bacterial infection | [18] | |
Discontinued Drug(s) | [+] 9 Discontinued Drugs | + | ||||
1 | 2085-P | Drug Info | Discontinued in Phase 3 | Otitis media | [19] | |
2 | DA-7101 | Drug Info | Discontinued in Phase 3 | Gram-positive bacterial infection | [20] | |
3 | P1A | Drug Info | Discontinued in Phase 2 | Toxicity | [21] | |
4 | BRL-42715 | Drug Info | Terminated | Bacterial infection | [22] | |
5 | CL-186659 | Drug Info | Terminated | Bacterial infection | [23] | |
6 | Ro-48-1220 | Drug Info | Terminated | Bacterial infection | [24] | |
7 | Ro-48-5545 | Drug Info | Terminated | Bacterial infection | [25] | |
8 | Ro-48-8724 | Drug Info | Terminated | Multidrug resistant infection | [26] | |
9 | SB-236049 | Drug Info | Terminated | Bacterial infection | [27] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Modulator | [+] 8 Modulator drugs | + | ||||
1 | Ceftolozane/tazobactam | Drug Info | [28] | |||
2 | CAZ AVI | Drug Info | [30] | |||
3 | CXL | Drug Info | [33] | |||
4 | 2085-P | Drug Info | [43] | |||
5 | P1A | Drug Info | [44] | |||
6 | CL-186659 | Drug Info | [43] | |||
7 | Ro-48-1220 | Drug Info | [46] | |||
8 | Ro-48-8724 | Drug Info | [48] | |||
Inhibitor | [+] 61 Inhibitor drugs | + | ||||
1 | Clavulanate | Drug Info | [29] | |||
2 | Meropenem + vaborbactam | Drug Info | [4] | |||
3 | Tazobactam | Drug Info | [1] | |||
4 | Enmetazobactam | Drug Info | [31] | |||
5 | Vaborbactam | Drug Info | [32] | |||
6 | MK-7655 | Drug Info | [34] | |||
7 | ETX0282 | Drug Info | [35] | |||
8 | ME-1071 | Drug Info | [36] | |||
9 | OP-0595 | Drug Info | [37] | |||
10 | QPX7728 | Drug Info | [38] | |||
11 | QPX7831 | Drug Info | [39] | |||
12 | VNRX-5133 | Drug Info | [41] | |||
13 | XNW4107 | Drug Info | [42] | |||
14 | DA-7101 | Drug Info | [20] | |||
15 | BRL-42715 | Drug Info | [45] | |||
16 | Ro-48-5545 | Drug Info | [47] | |||
17 | SB-236049 | Drug Info | [27] | |||
18 | (P-Iodophenylacetylamino)Methylphosphinic Acid | Drug Info | [49] | |||
19 | 1-Aminopropane-1,2,3-tricarboxylic acid | Drug Info | [50] | |||
20 | 2-(N-Morpholino)-Ethanesulfonic Acid | Drug Info | [49] | |||
21 | 2-(Sulfanylmethyl)phenylphosphonic acid | Drug Info | [51] | |||
22 | 2-mercaptophenylphosphonic acid | Drug Info | [51] | |||
23 | 2-Methyl-2,4-Pentanediol | Drug Info | [49] | |||
24 | 2-phenyl-1H-imidazole-4-carboxylic acid | Drug Info | [52] | |||
25 | 3-Amino-3-(methoxycarbonyl)-1,5-pentandioic acid | Drug Info | [50] | |||
26 | 3-ethoxycarbonylpyroglutamate | Drug Info | [50] | |||
27 | 3-Nitrophenylboronic Acid | Drug Info | [49] | |||
28 | 4,4'-Biphenyldiboronic Acid | Drug Info | [49] | |||
29 | 4-(Carboxyvin-2-Yl)Phenylboronic Acid | Drug Info | [49] | |||
30 | 4-Carboxyphenylboronic Acid | Drug Info | [49] | |||
31 | 4-iodo-acetamido phenylboronic acid | Drug Info | [49] | |||
32 | 4-Methyl-3-(2-oxo-azetidin-1-yl)-benzoic acid | Drug Info | [53] | |||
33 | 4-[(METHYLSULFONYL)AMINO]BENZOIC ACID | Drug Info | [52] | |||
34 | 5-Fluoro-2-sulfanyl-phenylphosphonic acid | Drug Info | [51] | |||
35 | 5-hydroxymethylbenzo[b]thiophen-2-ylboronic acid | Drug Info | [54] | |||
36 | 5-methyl-benzo[b]thiophen-2-ylboronic acid | Drug Info | [54] | |||
37 | Acetate Ion | Drug Info | [49] | |||
38 | Acylated Ceftazidime | Drug Info | [49] | |||
39 | Alpha-Sulfanyl(2,4-dichlorobenzyl)phosphonic acid | Drug Info | [51] | |||
40 | Alpha-Sulfanyl(2-methoxybenzyl)phosphonic acid | Drug Info | [51] | |||
41 | Alpha-Sulfanyl(4-bromobenzyl)phosphonic acid | Drug Info | [51] | |||
42 | Alpha-Sulfanyl(4-chlorobenzyl)phosphonic acid | Drug Info | [51] | |||
43 | Alpha-Sulfanyl(4-fluorobenzyl)phosphonic acid | Drug Info | [51] | |||
44 | Alpha-Sulfanylbenzylphosphonic acid | Drug Info | [51] | |||
45 | Alpha-Sulfanylpropylphosphonic acid | Drug Info | [51] | |||
46 | Benzo[b]thiophen-2-ylboronic acid | Drug Info | [49], [54] | |||
47 | Carbamic Acid | Drug Info | [49] | |||
48 | Clavulanate+Amoxicillin | Drug Info | [55] | |||
49 | Degraded Cephaloridine | Drug Info | [49] | |||
50 | Diisopropyl 1-mercaptopropylphosphonate | Drug Info | [51] | |||
51 | Diisopropyl 2-(sulfanylmethyl)phenylphosphonate | Drug Info | [51] | |||
52 | Diisopropyl mercapto(phenyl)methylphosphonate | Drug Info | [51] | |||
53 | Hydrolyzed Cephalothin | Drug Info | [49] | |||
54 | M-Aminophenylboronic Acid | Drug Info | [49] | |||
55 | N-2-Thiophen-2-Yl-Acetamide Boronic Acid | Drug Info | [49] | |||
56 | PCNOTAXIME GROUP | Drug Info | [52] | |||
57 | Sucrose | Drug Info | [56] | |||
58 | Thiophene-2-ylboronic acid | Drug Info | [54] | |||
59 | Tribenzyl 2-aminopropane-1,2,3-tricarboxylate | Drug Info | [50] | |||
60 | Triethyl 2-aminopropane-1,2,3-tricarboxylate | Drug Info | [50] | |||
61 | [[N-(Benzyloxycarbonyl)Amino]Methyl]Phosphate | Drug Info | [49] |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: Degraded Cephaloridine | Ligand Info | |||||
Structure Description | Structures of the acyl-enzyme complex of the staphylococcus aureus beta-lactamase mutant GLU166ASP:ASN170GLN with degraded cephaloridine | PDB:1GHM | ||||
Method | X-ray diffraction | Resolution | 1.86 Å | Mutation | Yes | [57] |
PDB Sequence |
KELNDLEKKY
40 NAHIGVYALD50 TKSGKEVKFN61 SDKRFAYAST71 SKAINSAILL81 EQVPYNKLNK 93 KVHINKDDIV103 AYSPILEKYV113 GKDITLKALI123 EASMTYSDNT133 ANNKIIKEIG 143 GIKKVKQRLK153 ELGDKVTNPV163 RYDIELQYYS173 PKSKKDTSTP183 AAFGKTLNKL 193 IANGKLSKEN203 KKFLLDLMLN213 NKSGDTLIKD223 GVPKDYKVAD233 KSGQAITYAS 243 RNDVAFVYPK253 GQSEPIVLVI263 FTNKDNKSDK273 PNDKLISETA283 KSVMKEF |
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Ligand Name: [[N-(Benzyloxycarbonyl)Amino]Methyl]Phosphate | Ligand Info | |||||
Structure Description | STRUCTURE OF A PHOSPHONATE-INHIBITED BETA-LACTAMASE. AN ANALOG OF THE TETRAHEDRAL TRANSITION STATE(SLASH)INTERMEDIATE OF BETA-LACTAM HYDROLYSIS | PDB:1BLH | ||||
Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [58] |
PDB Sequence |
KELNDLEKKY
40 NAHIGVYALD50 TKSGKEVKFN61 SDKRFAYAST71 SKAINSAILL81 EQVPYNKLNK 93 KVHINKDDIV103 AYSPILEKYV113 GKDITLKALI123 EASMTYSDNT133 ANNKIIKEIG 143 GIKKVKQRLK153 ELGDKVTNPV163 RYEIELNYYS173 PKSKKDTSTP183 AAFGKTLNKL 193 IANGKLSKEN203 KKFLLDLMLN213 NKSGDTLIKD223 GVPKDYKVAD233 KSGQAITYAS 243 RNDVAFVYPK253 GQSEPIVLVI263 FTNKDNKSDK273 PNDKLISETA283 KSVMKEF |
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Click to View More Binding Site Information of This Target with Different Ligands |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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There is no similarity protein (E value < 0.005) for this target
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Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Selection of TNF-alpha binding affibody molecules using a beta-lactamase protein fragment complementation assay. N Biotechnol. 2009 Nov 30;26(5):251-9. | |||||
REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
REF 3 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 065063. | |||||
REF 4 | 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85. | |||||
REF 5 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
REF 6 | ClinicalTrials.gov (NCT01644643) Ceftazidime-Avibactam for the Treatment of Infections Due to Ceftazidime Resistant Pathogens. U.S. National Institutes of Health. | |||||
REF 7 | ClinicalTrials.gov (NCT03687255) Safety and Efficacy Study of Cefepime-AAI101 in the Treatment of Complicated Urinary Tract Infections. U.S. National Institutes of Health. | |||||
REF 8 | ClinicalTrials.gov (NCT02166476) Efficacy/Safety of Meropenem-Vaborbactam Compared to Piperacillin-Tazobactam in Adults With cUTI and AP. U.S. National Institutes of Health. | |||||
REF 9 | Clinical pipeline report, company report or official report of AstraZeneca. | |||||
REF 10 | Clinical pipeline report, company report or official report of Merck (May 7, 2015). | |||||
REF 11 | ClinicalTrials.gov (NCT03491748) A Phase 1, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral ETX0282 Administered in Healthy Subjects. U.S.National Institutes of Health. | |||||
REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027139) | |||||
REF 13 | ClinicalTrials.gov (NCT02134834) A Phase I Study to Assess Safety, Tolerability and Pharmacokinetics of OP0595. U.S. National Institutes of Health. | |||||
REF 14 | ClinicalTrials.gov (NCT05072444) A Phase 1, Randomized, Double-Blind, Single-Dose, Drug-Drug Interaction Study to Determine the Impact of Co-administration of QPX7728 on the Pharmacokinetics of QPX2014 in Healthy Adult Subjects. U.S.National Institutes of Health. | |||||
REF 15 | ClinicalTrials.gov (NCT04578873) A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Single- and Multiple-Dose Study of the Safety, Tolerability, and Pharmacokinetics of Oral QPX7831 in Healthy Adult Subjects. U.S.National Institutes of Health. | |||||
REF 16 | Rapid, Sensitive Recovery of Recombinant Attenuated Salmonella enterica Serovar Typhi Vaccine Strains from Human Blood. Clin Vaccine Immunol. 2013 September; 20(9): 1473-1478. | |||||
REF 17 | ClinicalTrials.gov (NCT02955459) VNRX-5133 SAD/MAD Safety and PK in Healthy Adult Volunteers. U.S. National Institutes of Health. | |||||
REF 18 | ClinicalTrials.gov (NCT04802863) A Phase 1, Open-label Study to Evaluate the Safety and Intrapulmonary Pharmacokinetics of XNW4107, Imipenem and Cilastatin in Healthy Subjects. U.S.National Institutes of Health. | |||||
REF 19 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001248) | |||||
REF 20 | Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98. | |||||
REF 21 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020134) | |||||
REF 22 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001128) | |||||
REF 23 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004648) | |||||
REF 24 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004684) | |||||
REF 25 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008139) | |||||
REF 26 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008187) | |||||
REF 27 | Identification of a series of tricyclic natural products as potent broad-spectrum inhibitors of metallo-beta-lactamases. Antimicrob Agents Chemother. 2002 Jun;46(6):1880-6. | |||||
REF 28 | 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81. | |||||
REF 29 | A sensitive coupled HPLC/electrospray mass spectrometry assay for SPM-1 metallo-beta-lactamase inhibitors. Assay Drug Dev Technol. 2009 Apr;7(2):170-9. | |||||
REF 30 | NXL104 irreversibly inhibits the -lactamase from Mycobacterium tuberculosis. Biochemistry. 2012 Jun 5;51(22):4551-7. | |||||
REF 31 | Pharmacodynamics of Cefepime Combined with the Novel Extended-Spectrum--Lactamase (ESBL) Inhibitor Enmetazobactam for Murine Pneumonia Caused by ESBL-Producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2020 May 21;64(6):e00180-20. | |||||
REF 32 | Vaborbactam: Spectrum of Beta-Lactamase Inhibition and Impact of Resistance Mechanisms on Activity in Enterobacteriaceae. Antimicrob Agents Chemother. 2017 Oct 24;61(11):e01443-17. | |||||
REF 33 | Beta-Lactam Antibiotics Renaissance. Antibiotics. 2014, 3(2), 193-215. | |||||
REF 34 | Discovery of MK-7655, a beta-lactamase inhibitor for combination with Primaxin . Bioorg Med Chem Lett. 2014 Feb 1;24(3):780-5. | |||||
REF 35 | Interactions of the Diazabicyclooctane Serine beta-Lactamase Inhibitor ETX1317 with Target Enzymes. ACS Infect Dis. 2021 Jan 8;7(1):114-122. | |||||
REF 36 | Multidrug-resistant Gram-negative bacterial infections: are you ready for the challenge. Curr Clin Pharmacol. 2014 Feb;9(1):27-38. | |||||
REF 37 | OP0595, a new diazabicyclooctane: mode of action as a serine -lactamase inhibitor, antibiotic and -lactam 'enhancer'. J Antimicrob Chemother. 2015 Oct;70(10):2779-86. | |||||
REF 38 | QPX7728, An Ultra-Broad-Spectrum B-Lactamase Inhibitor for Intravenous and Oral Therapy: Overview of Biochemical and Microbiological Characteristics. Front Microbiol. 2021 Jul 5;12:697180. | |||||
REF 39 | Selection of QPX7831, an Orally Bioavailable Prodrug of Boronic Acid beta-Lactamase Inhibitor QPX7728. J Med Chem. 2021 Dec 9;64(23):17523-17529. | |||||
REF 40 | WO patent application no. 2010,0456,20, Recombinant bacterium capable of eliciting an immune response against streptococcus pneumoniae. | |||||
REF 41 | Discovery of Taniborbactam (VNRX-5133): A Broad-Spectrum Serine- and Metallo--lactamase Inhibitor for Carbapenem-Resistant Bacterial Infections. J Med Chem. 2020 Mar 26;63(6):2789-2801. | |||||
REF 42 | In vitro and in vivo activities of a novel beta-lactamase inhibitor combination imipenem/XNW4107 against recent clinical Gram-negative bacilli from China. J Glob Antimicrob Resist. 2022 Dec;31:1-9. | |||||
REF 43 | US patent application no. 2004,0023,290, Novel therapeutic agents that modulate enzymatic processes. | |||||
REF 44 | IPSAT P1A, a class A beta-lactamase therapy for the prevention of penicillin-induced disruption to the intestinal microflora. Curr Opin Investig Drugs. 2009 Aug;10(8):838-44. | |||||
REF 45 | In vitro evaluation of BRL 42715, a novel beta-lactamase inhibitor. Antimicrob Agents Chemother. 1989 Sep;33(9):1580-7. | |||||
REF 46 | Comparative in vitro activity of apalcillin alone and combined with Ro 48-1220, a novel penam beta-lactamase inhibitor. Clin Microbiol Infect. 1995 Feb;1(2):86-100. | |||||
REF 47 | Potentiation of beta-lactams against Pseudomonas aeruginosa strains by Ro 48-1256, a bridged monobactam inhibitor of AmpC beta-lactamases. J Antimicrob Chemother. 1997 Sep;40(3):335-43. | |||||
REF 48 | Activity of a broad-spectrum cephalosporin (Ro 48-8391) alone and in combination with two novel beta-lactamase inhibitors (Ro 48-5545 and Ro 48-8724). Diagn Microbiol Infect Dis. 1998 Oct;32(2):85-94. | |||||
REF 49 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
REF 50 | Discovery of novel lipophilic inhibitors of OXA-10 enzyme (class D beta-lactamase) by screening amino analogs and homologs of citrate and isocitrate. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3593-7. | |||||
REF 51 | Mercaptophosphonate compounds as broad-spectrum inhibitors of the metallo-beta-lactamases. J Med Chem. 2010 Jul 8;53(13):4862-76. | |||||
REF 52 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
REF 53 | N-aryl 3-halogenated azetidin-2-ones and benzocarbacephems, inhibitors of beta-lactamases. J Med Chem. 1988 Feb;31(2):370-4. | |||||
REF 54 | Optimizing cell permeation of an antibiotic resistance inhibitor for improved efficacy. J Med Chem. 2007 Nov 15;50(23):5644-54. | |||||
REF 55 | Emerging therapies for the treatment and prevention of otitis media. Expert Opin Emerg Drugs. 2006 May;11(2):251-64. | |||||
REF 56 | Ten S, Maclaren N: Insulin resistance syndrome in children. J Clin Endocrinol Metab. 2004 Jun;89(6):2526-39. | |||||
REF 57 | Structures of the acyl-enzyme complexes of the Staphylococcus aureus beta-lactamase mutant Glu166Asp:Asn170Gln with benzylpenicillin and cephaloridine. Biochemistry. 2001 Feb 27;40(8):2351-8. | |||||
REF 58 | Structure of a phosphonate-inhibited beta-lactamase. An analog of the tetrahedral transition state/intermediate of beta-lactam hydrolysis. J Mol Biol. 1993 Nov 5;234(1):165-78. |
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