Selected Review Articles on the Therapeutic Applications of Gallium

Bernstein LR (2013) Gallium, therapeutic effects, in Encyclopedia of Metalloproteins, Kretsinger RH, Uversky VN, and Permyakov EA, eds., pp. 823-835, Springer, New York.

Bernstein LR (2005) Therapeutic gallium compounds, in Metallotherapeutic Drugs and Metal-Based Diagnostic Agents: The Use of Metals in Medicine, Gielen M and Tiekink ERT, eds., pp. 259-277, Wiley, New York.

Bernstein LR (1998) Mechanisms of therapeutic activity for gallium. Pharmacological Reviews 50:665-682.

Anticancer Activity of Gallium Maltolate

Al-Gizawiy MM, Wujek RT, Alhajala HS, Cobb JM, Prah MA, Doan NB, Connelly JM, Chitambar CR, Schmainda KM (2024) Potent in vivo efficacy of oral gallium maltolate in treatment-resistant glioblastoma. Frontiers in Oncology 13:1278157. DOI: 10.3389/fonc.2023.1278157

Connelly J, Zoss CJ, Schmainda K, Al-Gizawiy M, Pinheiro FS, Chitambar C (2023) CTNI-57. Preliminary results of a Phase 1 trial of oral gallium maltolate in recurrent glioblastoma. Neuro-Oncology 25(Suppl 5):i39, DOI: 10.1093/neuonc/noad179.0339

Zoss CJ, Connelly J, Chitambar C, Schmainda K (2023) NIMG-09. Application of fractional tumor burden mapping to monitor glioblastoma progress in the Phase 1 trial of gallium maltolate. Neuro-Oncology 25(Suppl 5):i39, DOI: 10.1093/neuonc/noad179.0705

Al-Gizawiy M, Wujek R, Zoss CJ, Tanaka R, Mirza SP, Chitambar C, Schmainda K (2023) HGG-06. Characterization of the effect of the oral iron-mimetic gallium maltolate on pediatric glioblastoma growth in vivo. Neuro-Oncology 25(Suppl 1):i39, DOI: 10.1093/neuonc/noad073.155

Al-Gizawiy M, Wujek R, Zoss CJ, Tanaka R, Mirza SP, Chitambar C, Schmainda K (2023) ATRT-03. The oral iron-mimetic gallium maltolate inhibits ATRT in vivo – imaging and histological characterization. Neuro-Oncology 25(Suppl 1):i1, DOI: 10.1093/neuonc/noad073.003

Al-Gizawiy M, Wujek R, Prah M, Connelly J, Chitambar C, Schmainda K (2022) EXTH-16. The oral iron-mimetic gallium maltolate supresses treatment-resistant glioblastoma – in vivo validation. Neuro-Oncology 24(Suppl 7):vii212, DOI: 10.1093/neuonc/noac209.815.

Molino S, Chitambar CR (2020) Involvement of the lysosome in the cytotoxicity of gallium maltolate in human pediatric brain tumor cell lines [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020, Apr 27-28 and Jun 22-24, 2020, Philadelphia (PA); Cancer Research 80(16 Suppl):Abstract nr 4176.

Alhajala HS, Markley JL, Kim JH, Al-Gizawiy MM, Schmainda KM, Kuo JS, Chitambar CR (2020) The cytotoxicity of gallium maltolate in glioblastoma cells is enhanced by metformin through combined action on mitochondrial complex 1. Oncotarget 11:1531-1544.

Molino S, Al-Gizawiy MM, Knipstein J, Schmainda KM, Chitambar CR (2019) Gallium Maltolate as Treatment for Pediatric Glioma. 5th Pediatric Neuro-Oncology Basic and Translational Research Conference, San Francisco, CA, May 3-4, 2019, Poster HGG-05.

Chitambar CR, Al-Gizawiy MM, Alhajala HS, Pechman KR, Wereley JP, Wujek R, Clark PA, Kuo JS, Antholine WE, Schmainda KM (2018) Gallium maltolate disrupts tumor iron metabolism and retards the growth of glioblastoma by inhibiting mitochondrial function and ribonucleotide reductase. Molecular Cancer Therapeutics DOI: 10.1158/1535-7163.MCT-17-1009.

Al-Gizawiy M, Robert W, Alhajala H, Cobb J, Prah M, Mirza S, Chitambar C, Schmainda K (2018) Oral gallium maltolate impairs tumor growth and extends disease-​specific survival in a xenograft model of recurrent GBM. Neuro-Oncology 20(Suppl 6):vi95.

Wu X, Wang TW, Lessmann GM, Saleh J, Liu X, Chitambar CR, Hwang ST (2015) Gallium maltolate inhibits human cutaneous T-cell lymphoma tumor development in mice. Journal of Investigative Dermatology 135:877-884.

Bernstein LR, van der Hoeven JJM, Boer RO (2011) Hepatocellular carcinoma detection by gallium scan and subsequent treatment by gallium maltolate: rationale and case study. Anti-Cancer Agents in Medicinal Chemistry 11:585-590.

Chitambar CR, Purpi DP (2010) A novel gallium compound synergistically enhances bortezomib-induced apoptosis in mantle cell lymphoma cells. Leukemia Research 34:950-953.

Chitambar CR, Purpi DP, Woodliff J, Yang M, Wereley JP (2007) Development of gallium compounds for treatment of lymphoma: gallium maltolate, a novel hydroxypyrone gallium compound, induces apoptosis and circumvents lymphoma cell resistance to gallium nitrate. The Journal of Pharmacology and Experimental Therapeutics 322:1228-1236.

Chua MS, Bernstein LR, Li R, So SKS (2006) Gallium maltolate is a promising chemotherapeutic agent for the treatment of hepatocellular carcinoma. Anticancer Research 26:1739-1744.

Antimicrobial Activity of Gallium Maltolate

Taype-Huanca K, Osorio MI, Inostroza D, Leyva-Parra L, Ruíz L, Valderrama-Negrón A, Alvarado-Huayhuaz J, Yañez O, Tiznado W (2024) Deciphering the molecular interaction process of gallium maltolate on SARS-CoV-2 main and papain-like proteases: a theoretical study. Biophysica 4:182-194. doi: 10.3390/biophysica4020013

Visaggio D, Frangipani E, Hijazi S, Pirolo M, Leoni L, Rampioni G, Imperi F, Bernstein L, Sorrentino R, Ungaro F, Visca P (2021) Variable susceptibility to gallium compounds of major cystic fibrosis pathogens. ACS Infectious Diseases; doi: 10.1021/acsinfecdis.1c00409.

Bernstein LR, Zhang L (2020) Gallium maltolate has in vitro antiviral activity against SARS-CoV-2 and is a potential treatment for COVID-19. Antiviral Chemistry and Chemotherapy 28:1-4.

Cereceres S, Lan Z, Bryan L, Whitely M, Wilems T, Greer H, Alexander ER, Taylor RJ, Bernstein LR, Cohen N, Whitfield-Cargile C, Cosgriff-Hernandez E (2019) Bactericidal activity of 3D-printed hydrogel dressing loaded with gallium maltolate. APL Bioengineering 3, 026102; doi: 10.1063/1.5088801.

Piatek M, Griffith D, Kavanagh K (2019) Characterisation of the antimicrobial mode of action of gallium maltolate (poster). Irish Biological Inorganic Chemistry Society 3rd Symposium, Royal College of Surgeons in Ireland, Dublin, 29 November 2019.

Giacani L, Bernstein LR, Haynes AM, Godornes BC, Ciccarese G, Drago F, Parodi A, Valdevit S, Anselmi L, Tomasini CF, Baca AM (2019) Topical treatment with gallium maltolate reduces Treponema pallidum subsp. pertenue burden in primary experimental lesions in a rabbit model of yaws. PLoS Neglected Tropical Diseases 13(1): e0007076.

Hijazi S, Visaggio D, Pirolo M, Frangipani E, Bernstein L, and Visca P (2018) Antimicrobial Activity of Gallium Compounds on ESKAPE Pathogens. Frontiers in Cellular and Infection Microbiology 8:316. doi: 10.3389/fcimb.2018.00316.

Fecteau M, Aceto HW, Bernstein LR, Sweeney RW (2014) Comparison of the antimicrobial activities of gallium nitrate and gallium maltolate against Mycobacterium avium subsp. paratuberculosis in vitro. The Veterinary Journal 202:195-197.

Sampieri F, Allen AL, Alcorn J, Clark CR, Vannucci FA., Pusterla N, Mapes SM, Ball KR, Dowling PM, Thompson J, Bernstein LR, Gebhart CJ, Hamilton DL (2014) Efficacy of gallium maltolate against Lawsonia intracellularis infection in a rabbit model. Journal of Veterinary Pharmacology and Therapeutics 37:571-578.

Arnold CE, Bordin A, Lawhon SD, Libal MC, Bernstein LR, Cohen ND (2012) Antimicrobial activity of gallium maltolate against Staphylococcus aureus and methicillin-resistant S. aureus and Staphylococcus pseudintermedius: An in vitro study. Veterinary Microbiology 155:389-394.

Baldoni D, Steinhuber A, Zimmerli W, Trampuz A (2010) In vitro activity of gallium maltolate against Staphylococci in logarithmic, stationary, and biofilm growth phases: comparison of conventional and calorimetric susceptibility testing methods. Antimicrobial Agents and Chemotherapy 54:157-163.

Coleman M, Kuskie K, Liu M, Chaffin MK, Libal M, Giguère S, Bernstein LR, Cohen ND (2010) In vitro antimicrobial activity of gallium maltolate against virulent Rhodococcus equi. Veterinary Microbiology 146:175-178.

DeLeon K, Balldin F, Watters C, Hamood A, Griswold H, Sreedharan S, Rumbaugh KP (2009) Gallium maltolate treatment eradicates Pseudomonas aeruginosa infection in thermally injured mice. Antimicrobial Agents and Chemotherapy 53:1331-1337.

Martens RJ, Miller NA, Cohen ND, Harrington JR, Bernstein LR (2007) Chemoprophylactic antimicrobial activity of gallium maltolate against intracellular Rhodococcus equi. Journal of Equine Veterinary Science 27:341-345.

Harrington JR, Martens RJ, Cohen ND, Bernstein LR (2006) Antimicrobial activity of gallium against virulent Rhodococcus equi in vitro and in vivo. Journal of Veterinary Pharmacology and Therapeutics 29:121-127.

Anti-Inflammatory Activity of Gallium Maltolate

Lawless SP, Cohen ND, Lawhon SD, Chamoun-Emanuelli AM, Wu J, Rivera-Vélez A, Weeks BR, Whitfield-Cargile CM (2020) Effect of gallium maltolate on a model of chronic, infected equine distal limb wounds. PLoS ONE 15(6): e0235006. https://doi.org/10.1371/journal.pone.0235006.

Schwendner SW, Allamneni KP, Bendele A (2005) Oral gallium maltolate is efficacious in acute and chronic models of rheumatoid arthritis. Annals of the Rheumatic Diseases 64 (Suppl III):168.

Schwendner SW, Allamneni KP, Bendele A, Bucalo L, Sreedharan SP (2005) Efficacy of oral gallium maltolate in acute and chronic models of rheumatoid arthritis. FASEB Journal 19 (4, Suppl S, Part 1):A926.

Scientific Articles Specifically on Topical Gallium Maltolate

Lawless SP, Cohen ND, Lawhon SD, Chamoun-Emanuelli AM, Wu J, Rivera-Vélez A, Weeks BR, Whitfield-Cargile CM (2020) Effect of gallium maltolate on a model of chronic, infected equine distal limb wounds. PLoS ONE 15(6): e0235006. https://doi.org/10.1371/journal.pone.0235006.

Cereceres S, Lan Z, Bryan L, Whitely M, Wilems T, Greer H, Alexander ER, Taylor RJ, Bernstein LR, Cohen N, Whitfield-Cargile C, Cosgriff-Hernandez E (2019) Bactericidal activity of 3D-printed hydrogel dressing loaded with gallium maltolate. APL Bioengineering 3, 026102; doi: 10.1063/1.5088801.

Giacani L, Bernstein LR, Haynes AM, Godornes BC, Ciccarese G, Drago F, Parodi A, Valdevit S, Anselmi L, Tomasini CF, Baca AM (2019) Topical treatment with gallium maltolate reduces Treponema pallidum subsp. pertenue burden in primary experimental lesions in a rabbit model of yaws. PLoS Neglected Tropical Diseases 13(1): e0007076.

Bernstein LR (2018) Topical gallium maltolate as a possible alternative to opioids in the treatment of chronic pain. 17th World Congress on Pain, Boston, Massachusetts, 16 September 2018.

Hummig W, Neto JS, Benzecry de Almeida D, Bernstein LR (2016) Efficacy of topical gallium maltolate for neuropathic orofacial pain following surgery or radiotherapy. 16th World Congress on Pain, Yokohama, Japan, 27 September, 2016.

Bernstein LR (2014) Successful treatment of refractory trigeminal neuralgia with topical gallium maltolate. 15th World Congress on Pain, Buenos Aires, Argentina, 10 October, 2014.

Bernstein LR (2013) Gallium maltolate: a new topical analgesic agent. 4th International Congress on Neuropathic Pain, Toronto, Canada, 23-26 May, 2013.

Bernstein LR (2012) Successful treatment of refractory postherpetic neuralgia with topical gallium maltolate: Case report. Pain Medicine 13:915-918.

Veterinary Applications of Gallium Maltolate

Shaw SD, Arroyo LG, zur Linden A, Allen C, Giraldo A, Cohen ND (2020) Medical management of a large intra‐abdominal mass caused by Rhodococcus equi in a foal. Equine Veterinary Education: doi:10.1111/eve.13389

Lawless SP, Cohen ND, Lawhon SD, Chamoun-Emanuelli AM, Wu J, Rivera-Vélez A, Weeks BR, Whitfield-Cargile CM (2020) Effect of gallium maltolate on a model of chronic, infected equine distal limb wounds. PLoS ONE 15(6): e0235006. https://doi.org/10.1371/journal.pone.0235006.

Monk CS, Sweeney, RW, Bernstein LR, Fecteau M (2016) Serum and tissue concentrations of gallium after oral administration of gallium nitrate and gallium maltolate to neonatal calves. American Journal of Veterinary Research 77:151-155.

Cohen ND, Slovis NM, Giguère S, Baker S, Chaffin MK, Bernstein LR (2015) Gallium maltolate as an alternative to macrolides for treatment of presumed Rhodococcus equi pneumonia in foals. Journal of Veterinary Internal Medicine 29:932-939.

Sampieri F, Alcorn J, Allen AL, Clark CR, Vannucci FA, Pusterla N, Mapes S, Ball KR, Dowling PM, Thompson J, Bernstein LR, Gebhart CJ, Hamilton DL (2014) Pharmacokinetics of gallium maltolate in Lawsonia intracellularis-infected and uninfected rabbits. Journal of Veterinary Pharmacology and Therapeutics 37:486-499.

Arnold C, Chaffin MK, Cohen N, Fajt VR, Taylor RJ, Bernstein LR (2010), Pharmacokinetics of gallium maltolate after intragastric administration in adult horses. American Journal of Veterinary Research 71:1371-1376.

Chaffin MK, Fajt V, Martens RJ, Arnold CE, Cohen ND, O’Conor M, Taylor RJ, Bernstein LR (2010) Pharmacokinetics of an orally-administered methylcellulose formulation of gallium maltolate in neonatal foals. Journal of Veterinary Pharmacology and Therapeutics 33:376-382.

Martens RJ, Cohen ND, Fajt VR, Nerren JR, Chaffin MK, Taylor RJ, Bernstein LR (2010) Gallium maltolate: safety in neonatal foals following multiple enteral administrations. Journal of Veterinary Pharmacology and Therapeutics 33:208-212.

Martens RJ, Mealey K, Cohen ND, Harrington JR, Chaffin MK, Taylor RJ, Bernstein LR (2007) Pharmacokinetics of gallium maltolate after intragastric administration in neonatal foals. American Journal of Veterinary Research 68:1041-1044.

Martens RJ, Harrington JR, Cohen ND, Chaffin MK, Mealey K, Taylor RJ, Bernstein LR (2006) Gallium therapy: a novel metal-based antimicrobial strategy for potential control of Rhodococcus equi foal pneumonia. American Association of Equine Practitioners Proceedings 52:219-221.

General Scientific Articles on Gallium Maltolate

Enyedy ÉA, Dömötör O, Bali K, Hetényi A, Tuccinardi T, Keppler BK (2015) Interaction of the anticancer gallium(III) complexes of 8-hydroxyquinoline and maltol with human serum proteins. Journal of Biological Inorganic Chemistry 20:77-88.

Ball KR, Sampieri F, Chirino M, Hamilton DL, Blyth RI, Sham TK, Dowling PM, Thompson J (2013) Synchrotron X-ray fluorescence microscopy of gallium in bladder tissue following gallium maltolate administration during urinary tract infection. Antimicrobial Agents and Chemotherapy 57:5197-5201.

Bernstein LR, Tanner T, Godfrey C, Noll B (2000) Chemistry and pharmacokinetics of gallium maltolate, a compound with high oral gallium bioavailability. Metal Based Drugs 7:33-48.

Bernstein LR (1995) Powder x-ray crystallography of gallium 3-hydroxy-4-pyronates. Powder Diffraction 10:140-142.