Naphthofluorescein

Naphthofluorescein inhibits the interaction between HIF-1 and Mint3.Naphthofluorescein suppresses Mint3-dependent HIF-1 activity and glycolysis in cancer cells and macrophages without cytotoxicity in vitro and adverse effect in vivo[1]. Naphthofluorescein is also a fluorescent pH-sensitive probe that can be used for functional Cerenkov imaging[2].

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> HIF/HIF Prolyl-Hydroxylase

HIF-1[1]

Naphthofluorescein (compound 19) (0-10 μM; 24 hours) suppresses the HIF-1 reporter activity in a concentration-dependent manner[1]. Cell Viability Assay[1] Cell Line: HT1080 cells Concentration: 0-10 μM Incubation Time: 24 hours Result: Significantly suppressed the HIF-1 reporter activity in a concentration-dependent manner.

Naphthofluorescein (compound 19) (100 mg/kg; i.p.; once daily for 5 consecutive days followed by 2 days off for 2 weeks)does not show weight loss or apparent histological abnormalities in the lung, liver, and kidney, or cause cause severe adverse effects for at least 2 weeks in mice[1]. Naphthofluorescein (compound 19) (100 mg/kg; i.p.; once daily for 5 consecutive days followed by 2 days off for 2 weeks) strikingly suppresses the tumour growth of subcutaneously injected E0771 cells and significantly attenuates tumour growth of MDA-MB-231 and AsPC-1 cells in immunodeficient mice. In turn, naphthofluorescein does not attenuate tumour growth of FIH-1-depleted MDA-MB-231 cells[1]. Naphthofluorescein (compound 19) (100 mg/kg; i.p.; once daily for 5 consecutive days followed by 2 days off for 2 weeks) suppresses tumour growth in human cancer cells in an FIH-1-dependent manner[1]. Animal Model: Male C57BL/6J mice (8 weeks)[1] Dosage: 100 mg/kg Administration: i.p.; once daily for 5 consecutive days followed by 2 days off for 2 weeks Result: Neither showed weight loss or apparent histological abnormalities in the lung, liver, and kidney, or caused cause severe adverse effects for at least 2 weeks in mice. Animal Model: Female C57BL/6J mice (E0771) and BALB/c nude mice (HT1080, MDA-MB-231, and AsPC-1) (6 weeks)[1] Dosage: 100 mg/kg Administration: i.p.; once daily for 5 consecutive days followed by 2 days off for 2 weeks Result: Strikingly suppressed the tumour growth of subcutaneously injected E0771 cells and significantly attenuated tumour growth of MDA-MB-231 and AsPC-1 cells in immunodeficient mice. In turn, naphthofluorescein did not attenuate tumour growth of FIH-1-depleted MDA-MB-231 cells.

[1]. Sakamoto T, et al. Pharmacological inhibition of Mint3 attenuates tumour growth, metastasis, and endotoxic shock. Commun Biol. 2021;4(1):1165. Published 2021 Oct 7.

[2]. Arroyo AD, et al. Development of fluorinated naphthofluoresceins for Cerenkov imaging. J Fluor Chem. 2019;225:27-34.