CAS 1154757-24-0 Plazomicin (HCID 42613186)

기본 정보

CAS: 1154757-24-0
표준 SMILES: CN[C@@H]1[C@@H](O)[C@@H](O[C@@H]2[C@@H](O)[C@H](O[C@H]3OC(CNCCO)=CC[C@H]3N)[C@@H](N)C[C@H]2NC(=O)[C@@H](O)CCN)OC[C@]1(C)O
InChIKey: IYDYFVUFSPQPPV-PEXOCOHZSA-N
분자식: C25H48N6O10
평균 분자량: 592.7 g/mol
단동위원소 질량: 592.34319175

개요

Developed by Achaogen biopharmaceuticals, plazomicin is a next-generation aminoglycoside synthetically derived from [DB12604]. The structure of plazomicin was established via appending hydroxylaminobutyric acid to [DB12604] at position 1 and 2-hydroxyethyl group at position 6'. It was designed to evade all clinically relevant aminoglycoside-modifying enzymes, which contribute to the main resistance mechanism for aminoglycoside therapy. However, acquired resistance of aminoglycosides may arise through over expression of efflux pumps and ribosomal modification by bacteria, which results from amino acid or rRNA sequence mutations. Like other aminoglycosides, plazomicin is ineffective against bacterial isolates that produce 16S rRNA methyltransferases. Plazomicin mediates the antibacterial activity against pathogens including carbapenem-resistant (CRE) and extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. It mediates the antibacterial activity by binding to bacterial 30S ribosomal subunit and inhibiting protein synthesis. On June 28th, 2018, plazomicin sulfate was approved by the FDA for use in adult patients for the treatment of complicated urinary tract infections (cUTI) including Pyelonephritis. It is marketed as Zemdri and is administered via once-daily intravenous infusion.

이름 및 식별자

우선 이름: Plazomicin
IUPAC: (2S)-4-amino-N-[(1R,2S,3S,4R,5S)-5-amino-4-[[(2S,3R)-3-amino-6-[(2-hydroxyethylamino)methyl]-3,4-dihydro-2H-pyran-2-yl]oxy]-2-[(2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-(methylamino)oxan-2-yl]oxy-3-hydroxycyclohexyl]-2-hydroxybutanamide
영어명: Plazomicin
분자식: C25H48N6O10
분자량: 592.68

이름 및 동의어

Plazomicin1154757-24-0ACHN-490plazomicinaplazomicineplazomicinum(2S)-4-amino-N-[(1R,2S,3S,4R,5S)-5-amino-4-[[(2S,3R)-3-amino-6-[(2-hydroxyethylamino)methyl]-3,4-dihydro-2H-pyran-2-yl]oxy]-2-[(2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-(methylamino)oxan-2-yl]oxy-3-hydroxycyclohexyl]-2-hydroxybutanamideLYO9XZ250JACHN490Zemdri (plazomicin)DTXSID001031303(2S)-4-amino-N-((1R,2S,3S,4R,5S)-5-amino-4-(((2S,3R)-3-amino-6-((2-hydroxyethylamino)methyl)-3,4-dihydro-2H-pyran-2-yl)oxy)-2-((2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-(methylamino)oxan-2-yl)oxy-3-hydroxycyclohexyl)-2-hydroxybutanamide

이름 더 보기

Plazomicin APIIYDYFVUFSPQPPV-BPUQVFSTSA-NPirimicarb Impurity 9 (Ethirimol)O-2-AMino-2,3,4,6-tetradeoxy-6-[(2-hydroxyethyl)aMino]-α-D-glycero-hex-4-enopyranosyl-(1→4)-O-[3-deoxy-4-C-Methyl-3-(MethylaMino)-β-L-arabinopyranosyl-(1→6)]-N1-[(2S)-4-aMino-2-hydroxy-1-oxobutyl]-2-deoxy-D-streptaMineD-Streptamine, O-2-amino-2,3,4,6-tetradeoxy-6-[(2-hydroxyethyl)amino]-α-D-glycero-hex-4-enopyranosyl-(1→4)-O-[3-deoxy-4-C-methyl-3-(methylamino)-β-L-arabinopyranosyl-(1→6)]-N1-[(2S)-4-amino-2-hydroxy-1-oxobutyl]-2-deoxy-

물성

구조 계산 물성

XLogP: -6.2
극성 표면적: 269 Å²
수소 결합 공여자 수: 11
수소 결합 수용자 수: 15
회전 가능 결합 수: 13
무거운 원자 수: 41
형식 전하: 0
복잡도: 873

실험 및 물리화학적 성질

DrugsPharmaceuticals -> Listed in ZINC15

Human Drugs · 2건

Breast Feeding; Lactation; Milk, Human; Antibacterial Agents; Anti-Infective Agents; Aminoglycosides

Reserve group antibiotics

물리화학적 성질

녹는점: 185 °C · >185°C (dec.)
끓는 점: 896.4 · 896.4±65.0 °C(Predicted)
밀도: 1.4 · 1.40±0.1 g/cm3(Predicted)
저장 조건: -20 °C · Hygroscopic, -20°C Freezer, Under inert atmosphere
용해도: 물(약간 용해됨)
물리적 상태: 고체
산도 계수 (pKa): 13.11 · 13.11±0.20(Predicted)
색상: 옅은 노랑

안전 및 규제

독성 정보

HepatotoxicityIntravenous therapy with plazomicin has been linked to only rare instances of serum enzyme elevations (

Effects During Pregnancy and Lactation◉ Summary of Use during Lactation

화학 및 산업

약리 정보

ATC Code · 3건

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

J01GB14

Protein BindingThe extent of plasma protein binding in humans is approximately 20%. The degree of protein binding was concentration-independent across the range tested in vitro (5 to 100 mcg/mL).

Pharmacodynamics · 1건

Plazomicin exerts its antibacterial activity in a dose-dependent manner with a post-antibiotic effect ranging from 0.2 to 2.6 hours at 2X MIC against _Enterobacteriaceae_, as demonstrated by _in vitro_ studies. In clinical trials comprising of hospitalized adult patients with cUTI (including pyelonephritis), resolution or improvement of clinical cUTI symptoms and a microbiological outcome of eradication were observed at day 5 following the first dose administration of plazomicin. Plazomicin has shown to elicit nephrotoxic, ototoxic, and neuromuscular blocking effects. In clinical trials, it did not induce any clinically relevant QTc-prolonging effects.

Mechanism of Action · 1건

Plazomicin exerts a bactericidal action against susceptible bacteria by binding to bacterial 30S ribosomal subunit. Aminoglycosides typically bind to the ribosomal aminoacyl-tRNA site (A-site) and induce a conformational change to further facilitate the binding between the rRNA and the antibiotic. This leads to codon misreading and mistranslation of mRNA during bacterial protein synthesis. Plazomicin demonstrates potency against _Enterobacteriaceae_, including species with multidrug-resistant phenotypes such as carbapenemase-producing bacteria and isolates with resistance to all other aminoglycosides. Its antibacterial activity is not inhibited by aminoglycoside modifying enzymes (AMEs) produced by bacteria, such as acetyltransferases (AACs), phosphotransferases (APHs), and nucleotidyltransferases (ANTs). Plazomicin was shown to be effective against _Enterobacteriaceae_ in presence of some beta-lactamases. In clinical settings and _in vivo_, bacteria shown to be susceptible toward plazomicin include _Escherichia_ _coli_, _Klebsiella pneumoniae_, _Proteus mirabilis_, and _Enterobacter cloacae_. Other aerobic bacteria that may be affected by plazomicin are _Citrobacter freundii_, _Citrobacter koseri_, _Enterobacter aerogenes_, _Klebsiella oxytoca_, _Morganella morganii_, _Proteus vulgaris_, _Providencia stuartii_, and _Serratia marcescens_.

화합물 노트

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Plazomicin