A new transparent iridium oxide (IrO x ) film on fluorine-doped tin oxide (FTO) electrodes were achieved from a homogeneous precursor complex solution by employing a facile spin-coating technique. The composition of the nanostructure and crystallinity of the IrO x film is tunable by a simple annealing treatment of a compact complex layer, which is responsible for their significantly different electrocatalytic performances for water oxidation. Transmission electron microscopy (TEM) observations showed uniformly dispersed small IrO x nanoparticles of dimensions ca. 2–5 nm for the film annealed at 300 °C, and the nanoparticles gradually agglomerated to form relatively large particles at higher temperatures (400 and 500 °C). The IrO x films prepared at different annealing temperatures are characterized by Raman spectroscopic data to reveal intermediate IrO x (OH) y nanoparticles with two oxygen binding motifs: terminal hydroxo and bridging oxo at 300 and 350 °C annealing, via amorphous IrO x at 400 °C, transforming ultimately to crystalline IrO2 nanoparticles at 500 °C. Cyclic voltammetry suggests that the intrinsic activity of catalytic Ir sites in intermediate IrO x (OH) y nanoparticles formed at 300 °C annealing is higher in comparison with amorphous and crystalline IrO x nanoparticles. Electrochemical impedance data showed that the charge transfer resistance (R ct = 232 Ω) for the IrO x (OH) y film annealed at 300 °C is lower relative to that of films annealed at higher temperatures. This is ascribable to the facilitated electron transfer in grain boundaries between smaller IrO x particles to lead the efficient electron transport in the film. The high intrinsic activity of catalytic Ir sites and efficient electron transport are responsible for the high electrocatalytic performance observed for the intermediate IrO x (OH) y film annealed at 300 °C; it provides the lowest overpotential (η) of 0.24 V and Tafel slope of 42 mV dec–1 for water oxidation at neutral pH, which are comparable with values for amorphous IrO x ·nH2O nanoparticle films (40–50 mV dec–1) reported as some of the most efficient electrocatalysts so far.

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We report the first accessible channel-like open pore architecture of ordered 2D hexagonal mesoporous IrO2 films and its utilization as an efficient anode for electrocatalytic water oxidation. A well-ordered mesostructure of circa 7 nm pores were obtained by a facile one-pot soft-templating strategy, employing a [Ir(OH)6](2-) precursor stabilized by a triblock copolymer "Pluronic F127" as a pore-directing template. A mesoporous IrO2 film calcined at 400 °C (∼70 nm thick) affords a high surface area of 512 m(2)  cm(-3) and 2 times higher O2 evolution during the electrocatalytic water oxidation relative to an untemplated IrO2 coating film.

Despite the worldwide approval of three generations of EGFR tyrosine kinase inhibitors (TKI) for advanced nonsmall cell lung cancers with EGFR mutations, no TKI with a broad spectrum of activity against all clinically relevant mutations is currently available. In this study, we sought to evaluate a covalent mutation-specific EGFR TKI, TAS6417 (also named CLN-081), with the broadest level of activity against EGFR mutations with a prevalence of !1%. Lung cancer and genetically engineered cell lines, as well as murine xenograft models were used to evaluate the efficacy of TAS6417 and other approved/in-development EGFR TKIs (erlotinib, afatinib, osimertinib, and poziotinib). We demonstrate that TAS6417 is a robust inhibitor against the most common EGFR mutations (exon 19 deletions and L858R) and the most potent against cells harboring EGFR-T790M (first/second-generation TKI resistance mutation). In addition, TAS6417 has activity in cells driven by less common EGFR-G719X, L861Q, and S768I mutations. For recalcitrant EGFR exon 20 insertion mutations, selectivity indexes (wildtype EGFR/mutant EGFR ratio of inhibition) favored TAS6417 in comparison with poziotinib and osimertinib, indicating a wider therapeutic window. Taken together, we demonstrate that TAS6417 is a potent EGFR TKI with a broad spectrum of activity and a wider therapeutic window than most approved/in-development generations of EGFR inhibitors.Implications: TAS6417/CLN-081 is a potent EGFR TKI with a wide therapeutic window and may be effective in lung cancer patients with clinically relevant EGFR mutations.

Activating mutations in the gene are important targets in cancer therapy because they are key drivers of non-small cell lung cancer (NSCLC). Although almost all common EGFR mutations, such as exon 19 deletions and the L858R point mutation in exon 21, are sensitive to EGFR-tyrosine kinase inhibitor (TKI) therapies, NSCLC driven by EGFR exon 20 insertion mutations is associated with poor clinical outcomes due to dose-limiting toxicity, demonstrating the need for a novel therapy. TAS6417 is a novel EGFR inhibitor that targets EGFR exon 20 insertion mutations while sparing wild-type (WT) EGFR. In cell viability assays using Ba/F3 cells engineered to express human EGFR, TAS6417 inhibited EGFR with various exon 20 insertion mutations more potently than it inhibited the WT. Western blot analysis revealed that TAS6417 inhibited EGFR phosphorylation and downstream molecules in NSCLC cell lines expressing EGFR exon 20 insertions, resulting in caspase activation. These characteristics led to marked tumor regression in both a genetically engineered model and in a patient-derived xenograft model. Furthermore, TAS6417 provided a survival benefit with good tolerability in a lung orthotopic implantation mouse model. These findings support the clinical evaluation of TAS6417 as an efficacious drug candidate for patients with NSCLC harboring EGFR exon 20 insertion mutations..