Kerydin (tavaborole) / Pfizer - LARVOL DELTA

Repurposing tavaborole to combat resistant bacterial infections through competitive inhibition of KPC-2 and metabolic disruption. (PubMed, Bioorg Chem) - "In mouse intraperitoneal infection models, tavaborole effectively restored the efficacy of meropenem against CRE bacteria. These findings elucidate the synergistic mechanisms of tavaborole, expand its potential applications in anti-infection therapeutics, and provide a promising strategy for addressing CRE infections."

Journal • Infectious Disease • Metabolic Disorders • Pneumonia

Synthesis and Evaluation of Boron-Containing Heterocyclic Compounds with Antimicrobial and Anticancer Activities. (PubMed, Molecules) - "Organoboron compounds, especially those containing boronic acid and benzoxaborole in their structure, have been gaining prominence in medicinal chemistry, following the FDA approval of tavaborole for the treatment of onychomycosis and bortezomib for multiple myeloma. albicans, ATCC 90028; T. rubrum, ATCC 28189; and T. mentagrophytes, ATCC 11481), while the anticancer effect was evaluated against oral squamous cell carcinoma (SCC) cell lines. Several promising boron-containing prototypes were identified, providing a foundation for further molecular optimization in the development of new antimicrobial and anticancer compounds."

Journal • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Oral Cancer • Pulmonary Disease • Respiratory Diseases • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Tuberculosis

Evaluation of Efinaconazole as a Potential Armament Against Multidrug-Resistant Yeast Candida auris (AAD 2025) - "In a proof-of-concept study, efinaconazole possessed potent inhibitory activity against C. auris that was greater than fluconazole, itraconazole, and terbinafine [5]...The effect of efinaconazole will be compared with tavaborole against 15 clinically isolated strains of C. auris (10 antifungal resistant/5 antifungal susceptible based on preliminary screening)...Investigation of all 15 C. auris strains is ongoing and full results will be presented. Results from these in vitro analyses will provide important mechanistic information on the antifungal activity efinaconazole against antifungal-resistant C. auris strains, which represent a growing threat to public health."

Infectious Disease

In Vitro Activity of 4 Topical Antifungals Against the Terbinafine-Resistant Dermatophyte Species Trichophyton indotineae (AAD 2025) - "In preliminary findings, efinaconazole demonstrated potent antifungal activity against terbinafine-resistant T. indotineae strains that was 16- and 33-fold greater than ciclopirox and tavaborole, respectively. These findings suggest that efinaconazole may be effective in the treatment of onychomycosis associated with terbinafine-resistant T. indotineae infection, though clinical evaluation is warranted."

Preclinical • Dermatology • Infectious Disease

In vitro molecular assessment of Cryptosporidium parvum parasitic load on human ileocecal adenocarcinoma cell culture after targeting by tavaborole (AN2690). (PubMed, J Parasit Dis) - "Drug efficacy was evaluated by quantitative real time polymerase chain reaction (PCR). The molecular assessment revealed a statistically remarkable decrease in parasitic load under the effect of Tavaborole when compared to Nitazoxanide."

Journal • Preclinical • Oncology

AQbD integrated high-performance thin layer chromatographic method for quantitative estimation of Tavaborole in the presence of its degradants and the matrix of nanostructured lipid carriers. (PubMed, Drug Dev Ind Pharm) - "Validation results revealed the HPTLC method's specificity (peak purity ≥ 0.999), linearity over a concentration range of 2-10 μg/band, sensitivity (LOD 0.21 μg and LOQ 0.64 μg), accuracy (99.68 - 101.43%w/w), and precision (%RSD < 2.0). The developed robust stability-indicating HPTLC method was successfully implemented for the sustainable testing of the TAV in the NLC formulations and stability testing."

Journal • Infectious Disease

Combination of Low White Blood Cell Count and Impaired Renal Function Is a Risk Factor for Higher Concentrations of Venetoclax and Prolonged Neutropenia in AML Patients with Venetoclax Combined Regimen: Real World Experience in the Japanese Cohort (ASH 2024) - "Aim : Severe and prolonged neutropenia is one of the most critical adverse events associated with venetoclax (VEN) in combination with azacitidine (Aza)...Patients with WBC < 3000/ul and estimated GFR (eGFR) <60ml/min showed higher VEN AUC values compared to others (Low WBC and low eGFR : mean 38935 h・ug/l vs others : mean 26901 h・ug/l, p = 0.020)...And importantly, we discovered patients with low WBC count and low renal function could be risk factors for higher concentrations of VEN and, eventually, prolonged neutropenia. VEN intensity-guided adjustment might be worth considering to manage neutropenia for Asian AML populations, especially patients with low WBC and impaired renal function."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Disorders • Neutropenia

Clinical Application of Single-Cell MRD By Genotype and Phenotype in AML (ASH 2024) - "The majority of patients (61.9%) received induction with cytarabine and anthracycline, while 28.6% received hypomethylating agents and venetoclax while 9.5% received other therapies...A total of 61,858 cells were called (mean 2690 cells/sample)...In conclusion, we report that single-cell MRD multi-omics in AML was feasible in clinical practice and offered additional information above that received from MFC- and NGS-based MRD assays, either alone or in combination. Updated results from clinical outcomes will be presented."

Clinical • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CD34 • CDKN2A • DNMT3A • FLT3 • IDH1 • IDH2 • KIT • NPM1 • TP53 • U2AF1

New antibacterial candidates against Acinetobacter baumannii discovered by in silico-driven chemogenomics repurposing. (PubMed, PLoS One) - "Molecular docking studies elucidated the binding modes of tavaborole in the editing and active domains of leucyl-tRNA synthetase, providing insights into its structural basis for antimicrobial activity. Tavaborole shows promise as an antimicrobial agent for combating A. baumannii infections and warrants further investigation in preclinical studies."

Journal • Infectious Disease

A case of refractory onychomycosis caused by Kloeckera apiculata: Successful treatment with itraconazole. (PubMed, Med Mycol Case Rep) - "The diagnosis was ultimately confirmed by fungal nail plate culture, histopathology, and PCR. Whereas prior treatments with topical 5 % tavaborole solution, oral terbinafine, and oral fluconazole were ineffective, complete clinical and mycological cure was achieved with a 3-month course of oral itraconazole."

Journal • Dermatology • Infectious Disease

Transungual Penetration and Antifungal Activity of Prescription and Over-the-Counter Topical Antifungals: Ex Vivo Comparison. (PubMed, Dermatol Ther (Heidelb)) - "Among all antifungals tested, the ability to penetrate human toenails to inhibit growth of both T. rubrum and T. mentagrophytes was greatest for efinaconazole, followed by tavaborole. These results indicate superior transungual penetration of efinaconazole compared to the other antifungals, suggesting lower keratin binding in the nail."

Journal • Preclinical • Infectious Disease

Development and validation of the RP-HPLC method for quantification of tavaborole. (PubMed, Anal Methods) - "Validation of the developed HPLC method confirmed the system's suitability, precision, linearity, accuracy, FD, robustness, and results. All validation criteria for the technique were within acceptable limits."

Journal

Computational therapeutic repurposing of tavaborole targeting arginase-1 for venous leg ulcer. (PubMed, Comput Biol Chem) - "The RMSD, RMSF, SASA, RG, inter and intra H-bond, PCA, FEL, and MMBSA studies affirmed the ligand-protein and protein complex flexibility, compactness, binding energy, van der waals energy, and solvation dynamics. These results revealed the stability and the interaction of the ligand with the catalytic site of arginase 1 enzyme, triggering the study towards the VLU treatment."

Journal • Genetic Disorders • Obesity • Venous Ulcer

Invited Talk: Controlling Drug Release from Self-Assembled Peptide Hydrogels using Dynamic Covalent Bonding (ACS-Sp 2024) - "These functionalized hydrogels were then loaded with boronic acid-containing drugs, including (GSK656, bortezomib, tavaborole, and ixazomib), a modified small-molecule drug (1V209), two therapeutic antibodies (amivantamab and omodenbamab), and one antibody-drug conjugate (trastuzumab deruxtecan) and characterized in vitro and in vivo using mass spectrometry, circular dichroism, in vitro equilibration assays, in vivo mass spectrometry imaging, and pharmacokinetic studies in mice. Boronic acid-functionalized antibodies remained stable within the hydrogel and were released from the hydrogel depo over up to 8 weeks in vivo. These results indicate that SHA-functionalized hydrogels represent a robust and versatile platform for delivering a variety of drugs and may have the potential to enhance clinical drug efficacy through sustained and/or localized release."

Design, Synthesis, and Antifungal Activity of 3-Substituted-2(5H)-Oxaboroles. (PubMed, ACS Med Chem Lett) - "Two oxaboroles, tavaborole and crisaborole, were recently approved as topical treatments for onychomycosis and atopic dermatitis, respectively, warranting further studies into this privileged structural class. These oxaboroles were nonhemolytic and nontoxic to rat myoblast cells (H9c2). Structure-activity relationship studies suggest that planarity is important for antimicrobial activity, possibly due to the effects of extended conjugation between the oxaborole and benzene rings."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease

Treatment Options for Onychomycosis: Efficacy, Side Effects, Adherence, Financial Considerations, and Ethics. (PubMed, J Clin Aesthet Dermatol) - "Although topical (efinaconazole, tavaborole, ciclopirox), oral (terbinafine, itraconazole), and laser (1064nm Nd:YAG lasers, both short-pulsed and Q-switched lasers, carbon dioxide lasers, and the diode 870, 930nm) are the current Food and Drug Administration (FDA)-approved treatments for onychomycosis, they are just a fraction of available treatment options. New and emerging therapies including new topical and oral medications, combination therapy, photodynamic light therapy, procedural, supplements, over-the-counter medication, and plasma therapy are discussed in our review. Onychomycosis has high reinfection and recurrence rates, and the treatment remains challenging as treatment selection involves ethical, evidence-based decision-making and consideration of each individual patient's needs, adherence, budget, the extent of quality of life discomfort, and aesthetic goals, independent of potential financial benefits to the clinicians."

Adherence • Adverse events • Journal • Review • Cardiovascular • Dermatology • Diabetes • Infectious Disease • Metabolic Disorders • Peripheral Arterial Disease

Treatment of onychomycosis in an era of antifungal resistance: Role for antifungal stewardship and topical antifungal agents. (PubMed, Mycoses) - "Antifungal resistance among species of Trichophyton against terbinafine and itraconazole-the two most common oral treatments for onychomycosis and other superficial fungal infections caused by dermatophytes-has been detected around the globe. Topical ciclopirox, efinaconazole and tavaborole, delivered either alone or in combination with oral antifungals, have demonstrated efficacy in vitro against susceptible and/or resistant isolates of Trichophyton species, with low potential for development of antifungal resistance. Additional real-world long-term data are needed to monitor global rates of antifungal resistance and assess the efficacy of oral and topical antifungals, alone or in combination, in counteracting antifungal resistance in the treatment of onychomycosis."

Journal • Review • Infectious Disease

Retrospective analysis of onychomycosis prescribing patterns using the medicare part D prescribers database 2016-2020. (PubMed, Mycoses) - "Physicians demonstrated a strong consideration for price when selecting treatments, with the least expensive medications (ciclopirox and terbinafine) accounting for nearly 99% of all prescriptions. In contrast, the more costly medications (efinaconazole and tavaborole) were rarely prescribed. In addition, physicians often opted for the less costly generic versions of ciclopirox and itraconazole, prescribing them 99% and 91% of the time, respectively. Notably, physician assistants and nurse practitioners had higher overall increases in prescription rates, at 15%, compared to 1%-6% for other specialties. There are no recent United States onychomycosis guidelines, and our study emphasizes cost considerations when prescribing onychomycosis treatments."

Journal • Medicare • Reimbursement • Retrospective data • US reimbursement • Infectious Disease • Novel Coronavirus Disease

Individual Article: Updated Review of Topical Pharmaceuticals and Complementary and Alternative Medications for the Treatment of Onychomycosis in Both General and Special Populations in the United States. (PubMed, J Drugs Dermatol) - "Treatment options are limited, with only 3 topical anti-fungal medications garnering approval in the US within the last 25 years: ciclopirox, tavaborole, and efinaconazole. We discuss treatment efficacies, pharmacology, and use in special populations, as well as current evidence for complementary and alternative medicine.  J Drugs Dermatol. 2023;22:9(Suppl 1):s5-10."

Journal • Review • Infectious Disease

Towards new drug scaffolds: Properties, chemistry, and therapeutic potential of hemiboronic naphthoids (ACS-Fall 2023) - "The goal of this work is to develop new classes of boron-based drugs inspired by benzoxaborole, the core scaffold of tavaborole (antifungal) and crisaborole (atopic eczema treatment). Many scaffolds displayed drug-like properties, including high intestinal uptake and high metabolic stability, demonstrating their potential suitability for oral administration and a wider range of drug targets than currently accessible to known boron compounds. Lead compounds are currently undergoing structure optimization."

Atopic Dermatitis • Dermatology • Immunology

Synthesis, properties, and reactivity of Diazaborines: Phenolic bioisosteres with hydroxy exchange capability (ACS-Fall 2023) - "The potential of these heterocycles is exemplified by the success of the benzoxaborole ring system, which is present in the commercial pharmaceuticals tavaborole and crisaborole. In order to gain a better understanding of this new heterocycle, their acidic and aromatic properties have been interrogated through a combination of experimental, spectroscopic, and computational studies. The preparation and orthogonal functionalization of these compounds and the evaluation of their physical properties will allow for the synthesis of derivatives tailor-made for specific applications in medicinal chemistry and bioisosterism that are amenable to engineered gain-of-function through hydroxy group exchange and hydrogen bonding."

Repurposing High-Throughput Screening Identifies Unconventional Drugs with Antibacterial and Antibiofilm Activities against Pseudomonas aeruginosa under Experimental Conditions Relevant to Cystic Fibrosis. (PubMed, Microbiol Spectr) - "Based on the antibacterial activity, assessed spectrophotometrically against the prototype RP73 strain and 10 other CF virulent strains, and the toxic potential evaluated toward CF IB3-1 bronchial epithelial cells, five potential hits were selected for further analysis: the anti-inflammatory and antioxidant ebselen, the anticancer drugs tirapazamine, carmofur, and 5-fluorouracil, and the antifungal tavaborole. The mode-of-action studies revealed ebselen, carmofur, and tirapazamine targeted the cell membrane, increasing its permeability with subsequent cell lysis. These drugs are strong candidates for repurposing for treating CF lung P. aeruginosa infections."

Journal • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Oncology • Pulmonary Disease • Respiratory Diseases

A Cautionary Tale of Treatment Resistance at Annual Meeting (DermatologyTimes) - "'Onychomycosis should only be treated if there is a confirmatory diagnosis [via] fungal culture or PCR [polymerase chain reaction] positive of a dermatophyte confirmatory culture, and identification of pathogen is ideal,' Boni E. Elewski, MD..."

Media quote

Boron based small molecules as potential anti-cancer agents (ACS-Sp 2023) - "Bortezomib (proteasome inhibiting anti-cancer drug used for the treatment of multiple myeloma) and tavaborole (fungal enzyme leucyl-tRNA synthetase inhibitor, used for the treatment of onychomycosis) are couple of boronic acid based drugs that are currently in the market. We have been working on the synthesis of benzoboroxoles for the past several years and we have been able to develop synthetic methodologies for the preparation of diverse functionalized benzoboroxoles. The current poster will focus on our efforts involving the coupling of benzoboroxoes with the pharmacophores of other existing chemotherapeutic drugs as well as their cytotoxicity evaluation."

Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology

Discovery of Novel Pimprinine and Streptochlorin Derivatives as Potential Antifungal Agents. (PubMed, Mar Drugs) - "Molecular docking models indicate that compound 4a binds with leucyl-tRNA synthetase in a similar mode as AN2690, offering a perspective on the mode of action for the study of its antifungal activity. These results suggest that compounds 4a and 5a could be regarded as novel and promising antifungal agents against phytopathogens due to their valuable potency."

Journal