arylamidine (T-2307) / Fujifilm Holdings - LARVOL DELTA

A Novel Clinical Presentation: First Documented Case of Candida Auris Empyema Thoracis (ATS 2025) - "He was found to have pneumonia due to Pseudomonas, and was treated with parenteral cefepime...He was treated with meropenem, vancomycin, anidulafungin, and liposomal amphotericin B. The pleural C. auris strain was susceptible to anidulafungin (MIC = 0.25 ug/ml)...We await the results of ongoing clinical trials with newly developed phase 2 clinical trial antifungal agents such as fosmanogepix, ibrexafungerp, and T-2307, a novel arylamidine, for advances in anti-C. auris treatment options."

Clinical • Acute Kidney Injury • Diabetes • Diabetic Nephropathy • Infectious Disease • Metabolic Disorders • Pneumonia • Renal Disease • Respiratory Diseases • Septic Shock

Synthesis of Azirinyl Ethynyl Ketones and Their Use in the Preparation C(O)C≡CR-Substituted NH-Pyrroles/NH-Imidazoles and Azole-Azine/Azole-Azole Heterocyclic Hybrids. (PubMed, J Org Chem) - "Azirinyl ethynyl ketones containing only a C(O)C≡CR substituent at position 2 of the azirine ring are good precursors for obtaining α-C(O)C≡CR substituted NH-pyrroles and 5-[C(O)C≡CR]-substituted NH-imidazoles, reacting selectively only at the azirine moiety with 1,3-diketones and arylamidines, respectively. Various N-heterocyclic hybrids (pyrrole-pyrimidine, imidazole-pyrimidine, pyrrole-isoxazole, imidazole-isoxazole, pyrimidine-pyrrole-thiophene, pyrrole-pyrimidine-thiophene, imidazole-pyrimidine-thiophene, isoxazole-pyrrole-thiophene) have been prepared based on orthogonal or domino reactions of an azirine and C(O)C≡CR moieties of azirinyl ethynyl ketones."

Journal

New Ground in Antifungal Discovery and Therapy for Invasive Fungal Infections: Innovations, Challenges, and Future Directions. (PubMed, J Fungi (Basel)) - "With the increasing incidence of resistance pathogens, such as Candida auris and Aspergillus fumigatus, we assess emerging antifungal agents, including Ibrexafungerp, T-2307, and N'-Phenylhydrazides, which target diverse fungal cell mechanisms. Finally, we briefly examine the potential use of artificial intelligence (AI) in the development of new antifungal treatments, diagnoses, and resistance prediction, which provides powerful tools in the fight against fungal pathogens. Overall, we highlight the pressing need for continued research to advance antifungal treatments and improve outcomes for high-risk populations."

Journal • Review • Infectious Disease

Synthesis and in vitro leishmanicidal activity of novel N-arylspermidine derivatives. (PubMed, Bioorg Chem) - "The cyclic N-arylamidine directs the alkylation to the unsubstituted nitrogen and also provides the N-benzyl group present in the triamine after simultaneous reduction of the resulting quaternary salt 2 and the cyano group...The antileishmanial activity of the compounds would rely on the N-arylspermidine moiety, as assessed by evaluation of related substructures which were inactive. This first series of compounds, among which two derivatives (3b,h) displayed EC50 values comparable to Miltefosine, represent a good starting point for further studies and multiparametric optimization to obtain more potent and selective candidates for the treatment of this neglected tropical disease."

Journal • Preclinical • Infectious Disease

Ecotoxicity and Mutagenicity Assessment of Novel Antifungal Agents VT-1161 and T-2307. (PubMed, Molecules) - "Despite these favorable results, further research is needed to understand their environmental behavior, interactions, and potential resistance development among non-target species. Our findings highlight the importance of comprehensive environmental risk assessments to ensure the sustainable use of new antifungal agents."

Journal • CNS Disorders • Infectious Disease • Psychiatry

Cyclocondensation of 2-(α-Diazoacyl)-2H-azirines with Amidines in Diazo Synthesis of Functionalized Naphtho[1,2-d]imidazoles. (PubMed, J Org Chem) - "It involved a new reaction of arylamidines with 2-(α-diazoacyl)-2H-azirines giving 5-aryl-4-(α-diazoacyl)-1H-imidazoles under mild conditions in good yields...Additionally, variation of the substituents at position 5 of naphtho[1,2-d]imidazoles is possible through the formation of triflates and subsequent cross-coupling reactions. One more heterocyclic pharmacophoric skeleton, 3H-furo[3',2':3,4]naphtho[1,2-d]imidazole, was easily constructed from methyl 5-hydroxy-3H-naphtho[1,2-d]imidazole-4-carboxylates in a one-pot mode using O-alkylation with phenacyl bromides followed by base-induced intramolecular acyl substitution at room temperature with high yields."

Journal

Cryptococcosis and Cryptococcal Meningitis: A Narrative Review and the Up-to-Date Management Approach. (PubMed, Cureus) - "This narrative review provides an evidence-based summary of the current treatment modalities and future trial options, including newer ones, namely, 18B7, T-2307, VT-1598, AR12, manogepix, and miltefosine...The disease can easily evade diagnosis with subacute presentation. Despite the severity of the disease, treatment options for cryptococcosis remain limited, and more research is needed."

Journal • Review • CNS Disorders • Human Immunodeficiency Virus • Infectious Disease

Novel Therapeutic Approaches to Invasive Candidiasis: Considerations for the Clinician. (PubMed, Infect Drug Resist) - "These novel antifungal agents also represent interesting alternative options because of their acceptable oral bioavailability (ibrexafungerp and fosmanogepix) or their large interdose interval (once weekly intravenous administration for rezafungin) for prolonged and/or outpatient treatment of complicated IC. This review discusses the potential place of these novel antifungal drugs for the treatment of IC considering their pharmacologic properties and their preclinical and clinical data."

Journal • Review • Candidiasis

3-Substituted Blatter Radicals: Cyclization of N-Arylguanidines and N-Arylamidines to Benzo[e][1,2,4]triazines and PhLi Addition. (PubMed, J Org Chem) - "The resulting seven C(3)-substituted benzo[e][1,2,4]triazin-4-yls were analyzed by spectroscopic and electrochemical methods augmented with density functional theory (DFT) methods. Electrochemical data were compared to DFT results and correlated with substituent parameters."

Journal

The Arylamidine T-2307 as a Novel Treatment for the Prevention and Eradication of Candida tropicalis Biofilms. (PubMed, Int J Mol Sci) - "Active doses of T-2307 did not affect the viability of PNT1A cells, and drug concentrations of 0.005 or 0.01 µg mL inhibited the secretion of inflammatory cytokines. Taken together, these results provide new information on T-2307, indicating this drug as a new and promising alternative therapeutic option for the treatment of Candida infections."

Journal • Candidiasis • Infectious Disease • CXCL8 • IL10 • IL4

Future Fungal Fighters in Dermatology: Novel Antifungal Drug Pipeline. (PubMed, J Drugs Dermatol) - "Novel drugs in the pipeline include ME1111, MAT2203, rezafungin, ibrexafungerp, olorofim, fosmanogepix, MGCD290, VT-1161, NP213, T-2307, aureobasidin A, and nikkomycin Z. While most of these “future fungal fighters” have been developed to address invasive fungal infections (IFI), there is potential for dermatologists to benefit as these drugs may be adapted for superficial infections. 2022;21(5):496-501. doi:10.36849/JDD.6373."

Journal • Dermatology • Infectious Disease

A short, versatile route towards benzothiadiazinyl radicals. (PubMed, Chem Sci) - "A family of substituted 1,2,4-benzothiadiazine 1-chlorides have been prepared by treatment of N-arylamidines in neat thionyl chloride at reflux. The S(iv) 1-chlorides are readily reduced under mild conditions to persistent 1,2,4-benzothiadiazinyl radicals which have been characterised by EPR spectroscopy and cyclic voltammetry. Crystallographic studies on isolated radicals indicate that the radicals dimerise via pancake bonding in the solid-state, resulting in spin-pairing and net diamagnetism."

Journal

An aromatic imidazoline derived from chloroquinoline triggers cell cycle arrest and inhibits with high selectivity the Trypanosoma cruzi mammalian host-cells infection. (PubMed, PLoS Negl Trop Dis) - "Chloroquinoline and arylamidine moieties are separately found in various compounds reported for their anti-trypanosoma activities...Finally, A6 was effective against the infective forms of the parasite during the infection of the mammalian host cells at a nanomolar concentration (IC50(tryps) = 26.7 ± 3.7 nM), exhibiting a selectivity index (SI) of 5,170. Our data suggest that A6 is a promising hit against T. cruzi."

Journal • Infectious Disease

Advances in anti-fungal therapies. (PubMed, Mycopathologia) - "These include VT-1161 and VT-1598, modified azoles with a tetrazole metal-binding group; the echinocandin rezafugin; the novel β-1,3-d-glucan synthase inhibitor ibrexafungerp; fosmanogepix, a novel anti-fungal targeting Gwt1; the arylamidine T-2307; the dihydroorotate inhibitor olorofim; and the cyclic hexapeptide ASP2397. The available data including spectrum of activity, toxicity and stage of clinical development will be discussed for each of these so clinicians are aware of promising anti-fungal agents with a strong likelihood of clinical availability in the next 5-7 years."

Journal • Review

ATI-2307 Exhibits Equivalent Antifungal Activity in Cryptococcus neoformans Clinical Isolates With High and Low Fluconazole IC. (PubMed, Front Cell Infect Microbiol) - "No correlation between increased fluconazole minimum inhibitory concentration (MIC) and ATI-2307 or amphotericin B MIC was observed, suggesting that the cellular changes impacting fluconazole susceptibility did not impact the effectiveness of ATI-2307. Our results suggest that ATI-2307 is a promising new antifungal drug for use in the context of high fluconazole or other antifungal drug MICs and/or in combination drug therapy regimens."

Clinical • Journal

Review of T-2307, an Investigational Agent That Causes Collapse of Fungal Mitochondrial Membrane Potential. (PubMed, J Fungi (Basel)) - "Activity has also been reported against Cryptococcus species, and this has translated into in vivo efficacy in experimental models of invasive candidiasis and cryptococcosis. However, little is known regarding the clinical efficacy and safety of this agent, as published data from studies involving humans are not currently available."

Journal • Review • Candidiasis • Infectious Disease

Current and promising pharmacotherapeutic options for candidiasis. (PubMed, Expert Opin Pharmacother) - "New therapeutic approaches are presented including recent synthesized antifungal compounds (Enchochleated-Amphotericin B, tetrazoles, rezafungin, enfumafungin, manogepix and arylamidine); drug repurposing using a diversity of antibacterial, antiviral and non-antimicrobial drugs; combination therapies with different compounds or photodynamic therapy; and innovations based on nano-particulate delivery systems...The success of each antimicrobial agent brings strategic insights to the next phased approach in treatingCandida spp. infections."

Journal • Candidiasis • Complement-mediated Rare Disorders • Hepatology • Immune Modulation • Infectious Disease • Inflammation

Efficacy of T-2307, a novel arylamidine, against ocular complications of disseminated candidiasis in mice. (PubMed, J Antimicrob Chemother) - "We evaluated ocular fungal burden in mice infected with C. albicans that received treatment with antifungal agents [T-2307, liposomal amphotericin B (LAMB) or fluconazole] for 3 consecutive days...The ocular T-2307 trough concentration was maintained above the MIC in the infected mice. An in vitro biofilm inhibition experiment showed that T-2307 suppressed C. albicans biofilm formation at the sub-MIC level, which was comparable with amphotericin B. Given these results in experimental disseminated candidiasis, T-2307 may be an effective treatment against the complication of ocular candidiasis."

Journal • Preclinical • Candidiasis • Psychiatry

Innovative therapies for invasive fungal infections in preclinical and clinical development. (PubMed, Expert Opin Investig Drugs) - "It is imperative to expand the pipeline of antifungals to tackle emerging fungal resistance against conventional antimycotic drugs, toxicity and drug-drug interactions. This unmet medical need should not be underappreciated."

Journal

The novel arylamidine T-2307 selectively disrupts yeast mitochondrial function by inhibiting respiratory chain complexes. (PubMed, Antimicrob Agents Chemother) - "Additionally, we demonstrated that the inhibition of respiratory chain complexes by T-2307 resulted in a decrease in the intracellular ATP levels in yeast cells. These results indicate that the inhibition of respiratory chain complexes III and IV is a key for selective disruption of yeast mitochondrial function and antifungal activity."

Journal

Calcium mediated efficient synthesis of N-arylamidines from organic nitriles and amines. (PubMed, Org Biomol Chem) - "The reactivity of the amidines was further examined and the respective urea derivatives were achieved in excellent yields. The plausible mechanism involves the generation of an active calcium amido pre-catalyst that helps in the activation of nitriles in the reaction course."

Journal

Systemic Antifungal Agents: Current Status and Projected Future Developments. (PubMed) - Methods Mol Biol - "This chapter focuses on the currently available classes and representatives of systemic antifungal drugs in clinical use. We further discuss the unmet clinical needs in the antifungal research field; efforts in reformulation of available drugs such as Amphotericin B nanoparticles for oral drug delivery; development of new agents of known antifungal drug classes, such as albaconazole, SCY-078, and biafungin; and new drugs with novel targets for treatment of invasive fungal infections, including nikkomycin Z, sordarin derivatives, VT-1161 and VT-1129, F901318, VL-2397, and T-2307."

Journal • Biosimilar • Immunology

Metal-Free One-Pot Synthesis of N,N'-Diarylamidines and N-Arylbenzimidazoles from Arenediazonium Salts, Nitriles, and Free Anilines. (PubMed) - Org Lett - "A highly efficient and facile metal-free, one-pot reaction has been developed to afford diversely substituted N-arylbenzimidazoles through chemoselective in situ generation of N,N'-diarylamidines from arenediazonium salts, nitriles, and free anilines. The advantages of this protocol consist of the operationally easy and simple one-pot procedure under metal-free and mild conditions, the direct use of inexpensive and commercially available chemicals, and thus, a cost-effective and greener process."

Journal • Biosimilar

New quinoline-arylamidine hybrids: Synthesis, DNA/RNA binding and antitumor activity. (PubMed) - "The cell cycle arrest was investigated by flow cytometry and the obtained results indicate that the selected compounds, 2d, 2e, 8a, 10d, 10e, and 10f, induce changes in the cell cycle of treated cells, but the cycle phase distribution varies between them. A significant decrease in the number of cells in S phase (p < 0.001) was observed in all treated cells, but only 10d and 10f induce cell cycle arrest at G0/G1 phase, dominantly."

Journal • Biosimilar • Leukemia

Hope on the Horizon: Novel Fungal Treatments in Development. (PubMed, Open Forum Infect Dis) - "Among agents that target the cell wall, 2 glucan synthesis inhibitors are discussed (rezafungin and ibrexafungerp), as well as fosmanogepix and nikkomycin Z. Agents that target the cell membrane include 3 fourth-generation azoles, oral encochleated amphotericin B, and aureobasidin A. Among agents with intracellular targets, we will review olorofim, VL-2397, T-2307, AR-12, and MGCD290. In addition, we will describe neurapheresis, a device used as adjunctive therapy for cryptococcosis. With a field full of novel treatments for fungal infections, the future looks promising."

Journal • Review