Juq 395 |verified| Now
| Model | Pathogen | Dosing Regimen | Outcome | |-------|----------|----------------|---------| | (immunocompetent CD‑1 mice) | MRSA (ATCC 43300) | 10 mg kg⁻¹ i.p., q12 h, 48 h | 4.8 log₁₀ CFU reduction vs. untreated; comparable to linezolid (5.1 log₁₀). | | Neutropenic thigh (Swiss albino mice) | Klebsiella pneumoniae (NDM‑1) | 20 mg kg⁻¹ p.o., q8 h, 24 h | 3.2 log₁₀ reduction; synergy with colistin (FIC = 0.5). | | Galleria mellonella infection model | Acinetobacter baumannii (carbapenem‑resistant) | 5 mg kg⁻¹ i.p., q12 h | 85 % survival at 72 h vs. 20 % in control. | | Pharmacokinetics (rat, oral) | — | 30 mg kg⁻¹ | C_max = 3.1 µg mL⁻¹; AUC₀‑∞ = 28 µg·h mL⁻¹; t₁/₂ ≈ 8 h. |
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: Crystallography (2.1 Å resolution) reveals that Juq‑395 occupies a pocket adjacent to the catalytic Cys115, inducing a conformational shift that blocks substrate access without covalently modifying the cysteine. This allosteric mechanism is distinct from fosfomycin, which covalently alkylates Cys115. | Model | Pathogen | Dosing Regimen |
The structural novelty of Juq‑395 lies in its within the quinazolinone core, which enables a tight, non‑covalent interaction with the active site of MurA (enolpyruvyl‑shikimate‑phosphate synthase). This binding mode circumvents the classic resistance mechanism—production of β‑lactamases—because the target enzyme is not a β‑lactam substrate. | | Galleria mellonella infection model | Acinetobacter
: Inhibition of MurA halts synthesis of the lipid‑II precursor, leading to rapid cell‑wall depletion and osmotic lysis. Time‑kill curves show a ≥ 3 log₁₀ CFU mL⁻¹ reduction within 4 h against MRSA, Enterococcus faecium (VRE), and carbapenem‑resistant Enterobacter cloacae .
: Surface plasmon resonance (SPR) studies demonstrate a K_D of 4 nM, with a slow dissociation rate (k_off ≈ 1 × 10⁻³ s⁻¹), indicating a tight, quasi‑irreversible interaction.
In the rapidly expanding landscape of antimicrobial research, has emerged in the last few years as a promising synthetic compound with a unique mode of action against multidrug‑resistant (MDR) bacteria. First reported in a 2022 patent filing by the biotech firm JuqBio Inc. , Juq‑395 is a small‑molecule inhibitor that targets the bacterial cell‑wall biosynthetic pathway in a manner distinct from existing β‑lactams, glycopeptides, and newer lipoglycopeptides. Because antimicrobial resistance (AMR) is now a leading global health threat—estimated to cause 10 million deaths per year by 2050—new agents such as Juq‑395 are of considerable scientific, clinical, and economic interest.