Novobiocin

Novobiocin (Albamycin; Cathomycin) sodium is an orally active antibiotic and Hsp-90 antagonist that also inhibits the Polθ helicase/ATPase domain with IC₅₀ values of 24 μM and 15-17 μM, respectively. Novobiocin sodium binds to Hsp90, GyrB, and POLθ, inhibiting their ATPase activity and ssDNA binding. Novobiocin sodium inhibits molecular chaperone function and DNA repair, and induces apoptosis and genomic instability. Novobiocin sodium exhibits bactericidal and antiparasitic activities. Novobiocin sodium inhibits tumor growth in vivo. Novobiocin sodium is used for research on equine piroplasmosis, ovarian cancer, breast cancer, anthrax, and melioidosis^{[1][2][3][4][5][6]}. In Vitro:Novobiocin (1-200 μM; 96 h) sodium inhibits the growth of Theileria equi and Babesia caballi in a dose-dependent manner, with IC₅₀ values of 165 μM and 84.85 μM, respectively, and causes parasite death at high doses^[1].
Novobiocin (1-2000 μM; 24 h) sodium shows low cytotoxicity against horse PBMCs, with a CC₅₀ of 11.63 mM and an SSI of 70.47, indicating its safety for mammalian cells^[1].
Novobiocin (1-2000 μM; 90 min) sodium shows extremely low hemolytic activity against horse erythrocytes, with a CC₅₀ of 261.97 mM and an SSI of 1587, indicating its safety for host erythrocytes^[1].
Novobiocin sodium inhibits MMEJ repair but not HR repair in U2OS cells^[3].
Novobiocin sodium increases IR-induced RAD51 and γH2AX foci formation in U2OS cells^[3].
Novobiocin sodium induces chromosomal aberrations and radial chromosomes in BRCA1^-/- RPE1 cells^[3].
Novobiocin (120 nM-1 mM; 1 h pre-incubation, 2 h reaction) sodium is a non-ATP-competitive inhibitor of Polθ-ATPase activity^[4].
Novobiocin (4 mM; 30 min) sodium binds to the allosteric site of the Polθ-ATPase domain, affecting ATP hydrolysis and stabilizing the core of this domain^[4].
Novobiocin sodium blocks the binding of Polθ to ssDNA in vitro^[4].
Novobiocin (500 μM; 30 min) sodium stabilizes the Polθ-ATPase domain^[4].
Novobiocin (500 μM; 1 h) sodium promotes tetramerization of the Polθ-ATPase domain^[4].
Novobiocin (50-200 μM; 24 h) sodium blocks the binding of intracellular Polθ to ssDNA in a dose-dependent manner^[4].
Novobiocin (200 μM; 2 h) sodium treatment leads to the accumulation of ssDNA gaps in RPE1 TP53^-/- BRCA1^-/- cells^[4].
Novobiocin (1 day) sodium exhibits MIC values ranging from 0.25 to 16 μg mL^-1 against N. gonorrhoeae DSM9188 and its mutant strains derived from single-colony isolation, with its primary target being the ParE subunit of DNA topoisomerase IV^[2].
Novobiocin sodium exhibits low in vitro effective concentrations against both Bacillus anthracis and Burkholderia pseudomallei^[5].
Novobiocin sodium specifically inhibits the ATPase activity of purified POLθ in vitro, with an IC₅₀ of 24 μM^[3].
Novobiocin (12-14 days) sodium selectively reduces the viability of BRCA1^-/- and BRCA2^-/- RPE1 cells compared with isogenic WT cells^[3].
Novobiocin sodium shows increased resistance in POLQ-deficient U2OS cells^[3].
Novobiocin sodium acts synergistically with Rucaparib (HY-10617A) to reduce the survival rate of BRCA1^-/- RPE1 cells and decrease the IC₅₀ of Rucaparib^[3].
Novobiocin sodium synergizes with Olaparib in HR-deficient TOV21G + EV cells, reducing the IC₅₀ of Olaparib by more than 40-fold^[3].
Novobiocin sodium is cytotoxic to multiple PARPi-resistant clones derived from RPE1-BRCA1-/- cells^[3].
Novobiocin (25-100 μM) sodium induces dose-dependent apoptosis in BRCA1^-/- RPE1 cells but does not induce apoptosis in WT RPE1 cells^[3]. In Vivo:Novobiocin (5-100 mg/kg; i.p.; single administration) sodium shows no organ toxicity in mice at 50 mg/kg body weight, and this dose is considered the NOAEL^[1].
Novobiocin (100 mg/kg; i.p.; twice daily; 35 days) sodium strongly inhibits the growth of Brca1-deficient GEMM-derived tumors and extends overall survival by 3-fold compared with the vehicle group^[3].
Novobiocin (100 mg/kg; i.p.; twice daily; 4 weeks) sodium specifically inhibits the growth of FANCF-deficient HR-defective tumors in vivo ^[3].
Novobiocin (75 mg/kg; i.p.; twice daily; 4 weeks) sodium alone induces tumor regression and, in combination with Olaparib (HY-10162), achieves tumor regression in the HR-deficient DF83 PDX model^[3].
Novobiocin (75 mg/kg; i.p.; twice daily; 4 weeks) sodium significantly inhibits tumor growth in the PARPi-resistant DF59 PDX model^[3].
Novobiocin (75 mg/kg; i.p.; twice daily; 4 weeks) sodium does not inhibit tumor growth in the DF149 PDX model with normal HR function, which is associated with low POLθ expression^[3].
Novobiocin (1.25-2.5 mg; i.p.; 1-3 times) sodium confers high protection against lethal intraperitoneal B. pseudomallei infection in BALB/c mice and promotes sterile immunity in most surviving mice^[5].
Novobiocin (2.5 mg; i.p.; 2-5 doses) sodium significantly prolongs time to death but does not significantly improve overall survival in the highly lethal inhalational anthrax model in A/J mice^[5].
Novobiocin (2.5 mg; i.p.; 4 doses; 7 days) sodium provides 70% protection against lethal aerosolized B. pseudomallei infection in BALB/c mice, and bacterial burden is typically undetectable in the tissues of surviving mice^[5].
Novobiocin (2.5 mg; i.p.; 3 doses) sodium significantly synergizes with live attenuated vaccine, improving survival and prolonging time to death in a lethal aerosol B. pseudomallei model^[5].