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Chemical Structure| 4008-48-4 Chemical Structure| 4008-48-4

Structure of Nitroxoline
CAS No.: 4008-48-4

Chemical Structure| 4008-48-4

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Nitroxoline is an antibiotic towards gram negative bacilli and can to treat the urinary tract infections.

Synonyms: 8-Hydroxy-5-nitroquinoline; 5-Nitro-8-quinolinol; Nitroxoline, 5-nitrox, 5-NOK, Cysto-saar plus, Nibiol

4.5 *For Research Use Only !

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Product Citations

Product Citations

Williams, Michael J ; Ronayne, Conor T ; Schumacher, Tanner J ; Johnson, Kayla M ; Wittmer, Mattew D ; Johnson, Joseph L , et al.

Abstract: Reprogrammed cancer cell proliferation requires high levels of protein synthesis and concomitant folding and processing. N-terminal methionine amino peptidases (MetAP) are a class of enzymes that cleave the initiator methionine amino acids to allow for peptide maturation and co-translational processing. Specifically, based on its role in protein synthesis, MetAP2 has been found to be upregulated in cancer cells and has been explored as a potential anticancer target. Cellular perturbations that impinge on protein synthesis activate cellular stress pathways, including the integrated stress response and mTORC1. Nitroxoline, a MetAP2 inhibitor has been explored as an anticancer agent but is hampered by poor pharmacokinetic properties. Here, we synthesize a few O-substituted silyl and nonsilyl nitroxoline analogs to diversify the nitroxoline template to reduce metabolic vulnerability. In vitro MetAP2 and cancer cell proliferation inhibition assays demonstrate that synthesized analogs retain potency when compared to the parent nitroxoline. Mechanistically, we show that the lead candidate compound 3 and nitroxoline activate ATF4 mediated stress responses through non-canonical mTORC1. These results further implicate MetAP2 protein processing in mTORC1 nutrient sensing pathways and provide novel synthetic analogs of nitroxoline for potential cancer treatment.

Keywords: nitroxoline ; MetAP2 ; integrated stress response ; ATF4 ; mTORC1

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Product Details of Nitroxoline

CAS No. :4008-48-4
Formula : C9H6N2O3
M.W : 190.16
SMILES Code : OC1=C2N=CC=CC2=C([N+]([O-])=O)C=C1
Synonyms :
8-Hydroxy-5-nitroquinoline; 5-Nitro-8-quinolinol; Nitroxoline, 5-nitrox, 5-NOK, Cysto-saar plus, Nibiol
MDL No. :MFCD00006791
InChI Key :RJIWZDNTCBHXAL-UHFFFAOYSA-N
Pubchem ID :19910

Safety of Nitroxoline

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301+H311+H331-H315-H319-H335
Precautionary Statements:P261-P280-P305+P351+P338-P311
Class:6.1
UN#:2811
Packing Group:

Related Pathways of Nitroxoline

DNA

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
U251 glioblastoma cells 5–80 µg/mL 4-24 hours U251 cells were most sensitive to nitroxoline (IC50=6 mg/mL), with significant growth inhibition observed within 4 hours at 10 mg/mL. Neuro Oncol. 2015 Jan;17(1):53-62.
L-02 0.5, 8, 4, and 1 µM 48 hours Evaluate the cytotoxicity of ASN-1733, with an IC50 of approximately 49.61 µg/mL Emerg Microbes Infect. 2024 Dec;13(1):2294854.
T24/CIS cells 0, 2.5, 5, 10, 20, 40 μM 24, 48, 72 hours To evaluate the inhibitory effect of NTX on the proliferation of T24/CIS cells, results showed that NTX inhibited cell proliferation in a time- and dose-dependent manner. Int J Biol Sci. 2021 Jul 25;17(12):3255-3267.
T24/DOX cells 0, 2.5, 5, 10, 20, 40 μM 24, 48, 72 hours To evaluate the inhibitory effect of NTX on the proliferation of T24/DOX cells, results showed that NTX inhibited cell proliferation in a time- and dose-dependent manner. Int J Biol Sci. 2021 Jul 25;17(12):3255-3267.
UM-UC-3 20 µM 24 hours Evaluate migration capacity Int J Biol Sci. 2022 Aug 8;18(13):5207-5220.
T24 10 µM 24 hours Evaluate migration capacity Int J Biol Sci. 2022 Aug 8;18(13):5207-5220.
J82 20 µM 48 hours Analyze circRNA expression profile Int J Biol Sci. 2022 Aug 8;18(13):5207-5220.
U87 glioblastoma cells 5, 10, 20, 40, 60, 80, 100 mg/mL 24 hours Nitroxoline inhibited U87 cell proliferation in a dose-dependent manner (IC50=50 mg/mL). Low doses (5-20 mg/mL) induced G0/G1 cell-cycle arrest, while high doses (40-60 mg/mL) triggered apoptosis via caspase 3 activation and PARP cleavage. Neuro Oncol. 2015 Jan;17(1):53-62.
Treg 300 µM Nitroxoline significantly increased the ion-current through human K2P18.1 channels, leading to increased Treg numbers Cell Res. 2022 Jan;32(1):72-88.
BxPC-3 41.2 μM 48 hours Nitroxoline significantly decreased the viability of BxPC-3 cells with an IC50 value of 41.2 μM. J Exp Clin Cancer Res. 2018 Sep 21;37(1):236.
Capan-2 16.9 μM 48 hours Nitroxoline significantly decreased the viability of Capan-2 cells with an IC50 value of 16.9 μM. J Exp Clin Cancer Res. 2018 Sep 21;37(1):236.
AsPC-1 26.8 μM 48 hours Nitroxoline significantly decreased the viability of AsPC-1 cells with an IC50 value of 26.8 μM. J Exp Clin Cancer Res. 2018 Sep 21;37(1):236.
RWPE-1 10 μM 24, 48, 72, 96 h To evaluate the effects of Nitroxoline on the viability of RWPE-1 cells. Results showed that Nitroxoline had no significant cytotoxicity on normal RWPE-1 cells. Int J Biol Sci. 2019 Mar 9;15(5):919-928.
PC3 10 μM 24, 48, 72, 96 h To evaluate the effects of Nitroxoline on the viability of PC3 cells. Results showed that Nitroxoline significantly inhibited the viability of PC3 cells. Int J Biol Sci. 2019 Mar 9;15(5):919-928.
DU145 10 μM 24, 48, 72, 96 h To evaluate the effects of Nitroxoline on the viability of DU145 cells. Results showed that Nitroxoline significantly inhibited the viability of DU145 cells. Int J Biol Sci. 2019 Mar 9;15(5):919-928.
LNCaP 10 μM 24, 48, 72, 96 h To evaluate the effects of Nitroxoline on the viability of LNCaP cells. Results showed that Nitroxoline significantly inhibited the viability of LNCaP cells. Int J Biol Sci. 2019 Mar 9;15(5):919-928.
RM9-Luc-PSA 0-50 μM 24, 48, 72, 96 h To evaluate the effects of Nitroxoline on the viability and proliferation of RM9-Luc-PSA cells. Results showed that Nitroxoline significantly inhibited the viability and proliferation of RM9-Luc-PSA cells. Int J Biol Sci. 2019 Mar 9;15(5):919-928.
Acanthamoeba culbertsoni 1.17 ± 0.09 µM 96 hours Evaluation of Nitroxoline's inhibitory effect on A. culbertsoni trophozoites, IC50 of 1.17 ± 0.09 µM Antioxidants (Basel). 2023 Dec 6;12(12):2081.
Acanthamoeba castellanii L-10 2.85 ± 0.58 µM 96 hours Evaluation of Nitroxoline's inhibitory effect on A. castellanii L-10 trophozoites, IC50 of 2.85 ± 0.58 µM Antioxidants (Basel). 2023 Dec 6;12(12):2081.
Acanthamoeba quina 3.24 ± 0.56 µM 96 hours Evaluation of Nitroxoline's inhibitory effect on A. quina trophozoites, IC50 of 3.24 ± 0.56 µM Antioxidants (Basel). 2023 Dec 6;12(12):2081.
Acanthamoeba griffini 0.69 ± 0.01 µM 96 hours Evaluation of Nitroxoline's inhibitory effect on A. griffini trophozoites, IC50 of 0.69 ± 0.01 µM Antioxidants (Basel). 2023 Dec 6;12(12):2081.
Acanthamoeba polyphaga 0.95 ± 0.01 µM 96 hours Evaluation of Nitroxoline's inhibitory effect on A. polyphaga trophozoites, IC50 of 0.95 ± 0.01 µM Antioxidants (Basel). 2023 Dec 6;12(12):2081.
Acanthamoeba castellanii Neff 0.87 ± 0.19 µM 96 hours Evaluation of Nitroxoline's inhibitory effect on A. castellanii Neff trophozoites, IC50 of 0.87 ± 0.19 µM Antioxidants (Basel). 2023 Dec 6;12(12):2081.
HUVEC 5 µM 72 hours Nitroxoline induced premature senescence in HUVEC and increased p21 protein and mRNA levels. J Natl Cancer Inst. 2010 Dec 15;102(24):1855-73.
Human umbilical vein endothelial cells (HUVEC) 1.9 µM 24 hours Nitroxoline inhibited HUVEC proliferation with an IC50 of 1.9 µM. J Natl Cancer Inst. 2010 Dec 15;102(24):1855-73.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
ICR mice Urinary tract infection model Oral 10 mg/kg Two doses Evaluate the efficacy of ASN-1733 in the urinary tract infection model, showing reduction in bacterial load in urine and bladder Emerg Microbes Infect. 2024 Dec;13(1):2294854.
BALB/c nude mice T24/DOX and T24/CIS subcutaneous xenograft models Oral administration 40 mg/kg Once daily for two weeks To evaluate the anti-tumor effect of NTX in vivo, results showed that NTX significantly inhibited the growth of T24/DOX and T24/CIS tumors without significantly affecting mouse body weight. Int J Biol Sci. 2021 Jul 25;17(12):3255-3267.
Mice Genetically engineered PTEN-deleted/KRASG12D-overexpressing glioma model Intraperitoneal injection 80 mg/kg Daily for 14 days Nitroxoline stabilized tumor volume (vs doubling in controls) after 14 days, increased TUNEL+ cells (15-20% vs <5%), and elevated ADC values, indicating apoptosis induction and growth suppression. Neuro Oncol. 2015 Jan;17(1):53-62.
BALB/c nude mice Tail vein injection model Oral 30 mg/kg Fed every 2 days for 8 weeks Evaluate the inhibitory effect of Nitroxoline on bladder cancer metastasis Int J Biol Sci. 2022 Aug 8;18(13):5207-5220.
C57BL/6 mice Orthotopic prostate cancer model Intragastric 15 mg/kg On days 0, 1, 3, 4, 6, 7, 9, 10, 12, and 13 five times a week To evaluate the antitumor effect of Nitroxoline combined with PD-1 blockade in a prostate cancer mouse model. Results showed that the combination therapy significantly suppressed tumor growth, reduced tumor weight and serum PSA levels, and enhanced antitumor immunity. Int J Biol Sci. 2019 Mar 9;15(5):919-928.
Female athymic nude mice (BALB/c, nu/nu-NCr) Human breast cancer xenograft model Intraperitoneal injection 60 mg/kg Every other day for 30 days Nitroxoline significantly inhibited tumor growth, reducing tumor volume by 60%. J Natl Cancer Inst. 2010 Dec 15;102(24):1855-73.

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