Hydroxy Group Research Articles

Effect of hydroxy groups on structural, electronic, and biological properties of methyl carbazate containing hydroxy benzaldehyde-based imines. A combined experimental and theoretical investigation

Interactions present in differently substituted hydroxy based imine derivatives were characterised and identified by the utilisation of spectroscopic techniques in conjunction with X-ray crystallography and theoretical computations. All the target compounds ‘a-c’ crystallises in monoclinic crystal system with P21/c and C2/c space groups. CH…Pi and Pi…Pi interaction are the characteristic interactions present in the target compounds ‘a-c’ The most significant contributions to the crystal packing were found using Hirshfeld surface analysis, and potential contact points were identified. H…H, O…H and C…H contacts and π stacking interactions are the dominant contacts observed in all the crystals these results showed that hydrogen bonding and hydrophobic interactions were significantly present. Furthermore, investigations related to calculations of the molecular electrostatic potential and frontier molecular orbital (highest occupied–lowest unoccupied) were carried out for the optimised structure. The HOMO-LUMO energy gap made it possible to determine the molecule's chemical hardness, chemical inertness, electronegativity, and electrophilicity index, which showed its possible kinetic stability and reactivity. The target compounds' predicted activity spectra (PASS) showed that these compounds exhibit significant Testosterone 17beta-dehydrogenase (NADP+) inhibition activity, with Pa 7.18–7.95. Finally, Testosterone 17beta-dehydrogenase (NADP+) (PDB-ID 3KLP) was used to conduct molecular docking investigations of compounds ‘a-c’. Due to their tiny size and lack of rigidity, which enable them to bind well at any position, a and b exhibit higher binding free energies of -7.08 and -7.00 kcal/mol and inhibition constants of 0.1 and 1.2 µM than compound c.

Donor effect on the B ← N dative bond directed dye sensitized solar cell application

This paper shows the use of B ← N triel bonding interactions in dye-sensitized solar cells (DSSCs) through molecular modeling involving different donor groups based on acceptors like Borinic acids, Boronic acid, and Boric acid. Our computed data shows that Pyrrolizine donor-based dye sensitizers show better efficiency than the other donors used in this work due to their lower distortion between the acceptor and the rest part of the dye, which indicates easier transfer of electrons. We also observed that Borinic acid spacer-based dyes showed better injection (ΔGinject) and regeneration efficiency (ΔGregen) as well as better short-circuit current density (JSC) and open circuit voltage (VOC) which are important for the higher efficiency which is due to the increase of the B ← N bond distances as we increase the number of hydroxy groups from (OH)1 to (OH)3 resulting in lower charge transfer.

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus.

Drimane-type sesquiterpenoids (DMTs) are characterized by a distinctive 6/6 bicyclic skeleton comprising the A and B rings. While DMTs are commonly found in fungi and plants, their presence in bacteria has not been reported. Moreover, the biosynthetic pathways for DMTs have been primarily elucidated in fungi, with identified P450s only acting on the B ring. In this study, we isolated and characterized three bacterial DMTs, namely 3β-hydroxydrimenol (2), 2α-hydroxydrimenol (3), and 3-ketodrimenol (4), from Streptomyces clavuligerus. Through genome mining and heterologous expression, we identified a cav biosynthetic gene cluster responsible for the biosynthesis of DMTs 2-4, along with a P450, CavA, responsible for introducing the C-2 and C-3 hydroxy groups. Furthermore, the substrate scope of CavA revealed its ability to hydroxylate drimenol analogs. This discovery not only broadens the known chemical diversity of DMTs from bacteria, but also provides new insights into DMT biosynthesis in bacteria.

Improved flame resistance and thermal insulation properties of steel fireproof coatings based on polyvinyl alcohol @ expandable graphite

Intumescent fireproof coating (IFC) can effectively slow down the temperature rise of base materials by constructing intumescent heat isolation chars. Expandable graphite (EG), combined with a typical intumescent flame-retardant system, shows an excellent expansion effect. However, it is difficult to be evenly dispersed in the coating system due to its low surface energy, thus limiting its application in IFC. In this research, EG encapsulated by polyvinyl alcohol (PVA) film was used in combination with conventional intumescent flame retardants to prepare a fireproof coating. Due to the increased hydrophilicity caused by the hydroxy groups of the PVA, both the dispersion and adhesion of EG can be greatly improved in the coating. Additionally, PVA also plays the role of a charring agent to further upgrade the quality of the produced carbon layer. The prepared IFC displays a satisfying synergistic effect. The experimental results showed that the back-surface temperature of the steel plate coated by PVA@EG was reduced to 232 °C after 20 min, far lower than the 250 °C of the unmodified EG system, and the thermal insulation performance was enhanced significantly. Compared with the untreated EG coating, the HRR, THR, and TSR decreased by 79.5 %, 86.0 % and 24.8 %, respectively, and combustion and smoke suppression performance were improved greatly. All in all, PVA@EG endows the coating with superior flame-retardant and thermal insulation performance and greatly improves the safety of steel structures in buildings.

Epoxide Ring‐Opening Reactions for Abundant Production of Mugineic Acids and Nicotianamine Probes

AbstractA succinct synthetic approach to mugineic acids and 2’‐hydroxynicotianamine was established. Unlike all other synthetic methods, this approach utilized epoxide ring‐opening reactions to form two C−N bonds and is characterized by the absence of redox reactions. Mugineic acid was synthesized from three readily available fragments on a gram scale in 6 steps. The protected 2’‐hydroxynicotianamine was also synthesized in 4 steps, and the dansyl group, serving as a fluorophore, was introduced through a click reaction after propargylation of the 2’‐hydroxy group. The dansyl‐labeled nicotianamine (NA) iron complexes were internalized by oocytes overexpressing ZmYS1 (from maize) or PAT1 (from human) transporters, indicating successful transport of the synthesized NA‐probe through these transporters.

Molecular Iodine as a Catalyst for Alkene Difluorination.

The difluorination reaction of alkenes catalyzed by molecular iodine was revealed for the first time. This difluorination reaction affords a simple and practical experimental method and can be applied to many aliphatic and aromatic alkenes bearing synthetically useful functional groups, such as ester, amide, hydroxy, and aryl groups. Preliminary mechanistic studies of this alkene difluorination suggest the existence of two catalytic cycles: the IF-driven cycle and the catalytic cycle by the IF adduct.

Biological activity and computational analysis of novel acrylonitrile derived benzazoles as potent antiproliferative agents for pancreatic adenocarcinoma with antioxidative properties

Continuing our research into the anticancer properties of acrylonitriles, we present a study involving the design, synthesis, computational analysis, and biological assessment of novel acrylonitriles derived from methoxy, hydroxy, and N-substituted benzazole. Our aim was to examine how varying the number of methoxy and hydroxy groups, as well as the N-substituents on the benzimidazole core, influences their biological activity. The newly synthesized acrylonitriles exhibited strong and selective antiproliferative effects against the Capan-1 pancreatic adenocarcinoma cell line, with IC50 values ranging from 1.2 to 5.3 μM. Consequently, these compounds were further evaluated in three other pancreatic adenocarcinoma cell lines, while their impact on normal PBMC cells was also investigated to determine selectivity. Among these compounds, the monohydroxy-substituted benzimidazole derivative 27 emerged with the most profound and broad-spectrum anticancer antiproliferative activity being emerged as a promising lead candidate. Moreover, a majority of the acrylonitriles in this series exhibited significant antioxidative activity, surpassing that of the reference molecule BHT, as demonstrated by the FRAP assay (ranging from 3200 to 5235 mmolFe2+/mmolC). Computational analysis highlighted the prevalence of electron ionization in conferring antioxidant properties, with computed ionization energies correlating well with observed activities.

Antimicrobial spiroketal macrolides and dichloro-diketopiperazine from Micromonospora sp. FIMYZ51

Four compounds (1–4) featuring with an L-rhodinose and spiroketal, possess uncommon continuous hydroxy groups in the macrolide skeleton, and a dichloro-diketopiperazine (5) were isolated from a marine derived Micromonospora sp. FIMYZ51. The determination of the relative and absolute configurations of all isolates was achieved by extensive spectroscopic analyses, single-crystal X-ray diffraction analysis, and ECD calculations. According to structural characteristic and genomic sequences, a plausible biosynthetic pathway for compound 1-4 was proposed and a spirocyclase was inferred to be responsible for the formation of the rare spirocyclic moiety. Compounds 1-4 exhibited potent antifungal activities which is equal to itraconazole against Aspergillus niger. Compounds 1-5 exhibited different degree of inhibitory activities against opportunistic pathogenic bacteria of endocarditis (Micrococcus luteus) with MIC values ranging from 0.0625 μg/mL to 32 μg/mL. Compounds 2 and 3 showed moderate cytotoxicity against drug-resistant tumor cell lines (Namalwa and U266). The result not only provides active lead-compounds, but also reveal the potential of the spirocyclase gene resources from Micromonospora sp., which highlights the promising potential of the strain for biomedical applications.

Water Adsorption on π-Surfaces of Open-Fullerenes.

Understanding the water adsorptive behavior of fullerenes is of particular importance for their material application in aqueous media. The conventional fullerenols usually provide complex physical pictures of water adsorption due to their uncontrollable hydroxylation degree and substitution pattern. Herein, we focus on poorly hydroxylated fullerenes with well-defined structures. The water adsorptive behavior was examined by synchrotron IR spectroscopy and computational studies. As a result, three types of IR bands were observed for adsorbed water. The population of the three states was considerably altered by the orientational difference of the hydroxy groups. Nevertheless, water adsorption could not occur for 9-fluorenol and catechol. This indicates that the Lewis acidic fullerene π-surface plays a prominent role in water adsorption, while the rather Lewis basic π-surface of 9-fluorenol is unable to attract much water at a boundary with humid air.

Comparing the crystal structures and spectroscopic properties of a p-hydroxy styrylquinolinium dye with those of its p-dimethylamino analogue

Two previously synthesized styrylquinolinium dyes, namely (E)-1-butyl-4-(4-(dimethylamino)styryl)quinolinium iodide (D36) and (E)-1-butyl-4-(4-hydroxystyryl)quinolinium iodide (D34), were compared in terms of their properties by single-crystal X-ray diffraction (XRD), Hirshfeld surface analysis, Fourier transform Raman (FT-Raman), Fourier transform infrared (FT-IR), fluorescence, and ultraviolet–visible (UV–Vis) spectroscopy, and 1H- and 13C-NMR methods. Both dyes D36 and D34 crystallized in the triclinic and monoclinic systems in the centrosymmetric space groups P-1 and P21/n, respectively. The unit cell of D36 contains two molecules of the dye, participating in weak intermolecular interactions, whereas that of D34 contains four formula units. The phenolic hydroxy group of D34 participates in the formation of a hydrogen bond with the iodide anion. The 4-styrylquinolinium moieties of the cationic dye molecules are nearly planar. The dihedral angle between the mean planes through the ten-membered quinolinium system and the benzene ring is 7.5° in D36 and 5.9(1)° in D34. The structural parameters planarity and bond length alternation (BLA) are discussed, which are important for the evaluation of the first hyperpolarizability β at the molecular level, even in a centrosymmetric crystal. The UV–visible spectra of the dyes in 14 solvents of different polarities were investigated. The reversible solvatochromic behavior of the dyes is demonstrated experimentally and compared with known “binuclear dyes” by evaluating the Rezende model. Dye D36 does not fluoresce, and D34 has a very low emission in the solvents tested.

Novel acrylonitrile derived imidazo[4,5-b]pyridines as antioxidants and potent antiproliferative agents for pancreatic adenocarcinoma

We present the design, synthesis, computational analysis, and biological assessment of several acrylonitrile derived imidazo[4,5-b]pyridines, which were evaluated for their anticancer and antioxidant properties. Our aim was to explore how the number of hydroxy groups and the nature of nitrogen substituents influence their biological activity. The prepared derivatives exhibited robust and selective antiproliferative effects against several pancreatic adenocarcinoma cells, most markedly targeting Capan-1 cells (IC50 1.2–5.3 μM), while their selectivity was probed relative to normal PBMC cells. Notably, compound 55, featuring dihydroxy and bromo substituents, emerged as a promising lead molecule. It displayed the most prominent antiproliferative activity without any adverse impact on the viability of normal cells. Furthermore, the majority of studied derivatives also exhibited significant antioxidative activity within the FRAP assay, even surpassing the reference molecule BHT. Computational analysis rationalized the results by highlighting the dominance of the electron ionization for the antioxidant features with the trend in the computed ionization energies well matching the observed activities. Still, in trihydroxy derivatives, their ability to release hydrogen atoms and form a stable O–H⋯O•⋯H–O fragment upon the H• abstraction prevails, promoting them as excellent antioxidants in DPPH• assays as well.

Isatogenols as Precursors for the Synthesis of Fully Substituted Indolines through Regio- and Stereoselective [3 + 2] Cycloaddition Using Various Olefins.

Here, we describe a unique reactivity of isatogen derivatives bearing a hydroxy group at the C3-position (isatogenol) and their synthetic application to highly regio- and stereoselective [3 + 2] cycloaddition reactions. This method provides facile access to polyfused and highly functionalized heterocycles including consecutive stereocenters. Furthermore, DFT calculations revealed that hydrogen bonding is a key to controlling the regio- and stereoselectivity in the cycloaddition using acrylates.

Alginate-based water-soluble adhesives: effect of incorporated phenolic hydroxy groups on adhesiveness

Abstract Alginic acid (Alg) was modified with tyramine (TA), homoveratrylamine (HVTA), and 2-phenylethylamine (PA) to obtain Alg-based adhesives, AlgTA, AlgHVTA, and AlgPA. The adhesiveness of the modified Algs were evaluated and compared with previously reported catechol-modified alginate, AlgDA. AlgTA showed adhesion tendency differently from AlgDA, depending on the incorporation ratios of TA. AlgHVTA with protected phenolic hydroxy groups showed lower adhesiveness than AlgDA for mica surfaces, but higher for polymethyl methacrylate surfaces. AlgPA without a phenolic hydroxy group also exhibited moderate adhesiveness for mica.

Identification of Phormidium sp, (kützing ex Gomont 1892): a potential exopolymer for effective bioremediation

The autotrophic cyanobacterium Phormidium sp. is filamentous, blue-green, sheath-prominent, and trichome-constricted. DNA barcoding of the 16S rRNA sequence was submitted to NCBI-GenBank under the accession number MW436689, with a similarity of 97–99% with varied sequences. The Phormidium sp. barcode region had a high G + C content (52.7%). An investigation is underway to extract and characterize exocellular polymeric substances from Phormidium sp. (EPS-P) for efficacy analysis. FTIR, GC-MS, and NMR were used to characterize (EPS-P). FTIR suggests the presence of hydroxy groups (O-H moieties) and amine salts (N-H). GCMS shows D-galactose, L-rhamnose, D-mannose, uronic acid, and D-glucuronic acid. The specific chemical shifts could be identified in the 1H NMR spectra. EPS has been used in a variety of industrial and environmental applications. The ability to emulsify EPS-P (0.1%) was analyzed with various oils. The emulsifying index (EI) was observed to be gingelly oil > brake oil > neem oil > coconut oil > petrol oil > diesel oil (EI24-EI120 hours). EPS-P performed bio-flocculating activity at various concentrations (10-50 mg mL1). The flocculating activity of EPS-P shows 89.5% at 50 mg ml−1. The EPS-P could be an excellent candidate for bio-flocculation and bio-emulsification aspects that are also eco-friendly.

Graphene oxide under the nanoscope: A comprehensive study of nanoindentation behavior

Graphene oxide membranes are expected to become one of the most important materials for technological applications due to their highly reactive surface, being directly related to their atomistic configuration. The understanding of its structure and physicochemical properties under mechanical deformation is becoming crucial in the development of new applications; however, the role of the different functional groups in the membrane and their response to external factors like indentation is still unclear. Nanoindentation experiments show elastic behavior when the penetration is small compared to the indenter radius and the membrane diameter. Molecular Dynamics simulations for large 3-layer graphene oxide membranes were carried out for a 50% oxidation content and the inclusion of epoxy and hydroxy groups. Simulations showed an elastic modulus similar to experimental values. After the elastic regime, the mechanical behavior is dominated by the evolution of functional groups. A quasi-elastic regime is uncovered, where unloading leads to self-healing of broken bonds. Finally, large indenter penetration leads to fracture, with fracture stress similar to experimental values.

Preparation and Structures of Multicomponent Crystals Composed of Heteroaromatic Cations, p‐Toluenesulfonate Anion, and Aromatic Hydrogen‐Bond Donors

AbstractCocrystals with three π‐components, which were a π‐cation, a π‐anion acting as a hydrogen‐bond acceptor, and a π‐molecule acting as a hydrogen‐bond donor, were prepared by the solution‐growth methods. The first and second components were ion pairs of 1‐methylpyridinium or 1‐methylquinolinium p‐toluenesulfonate derivatives, and the third components were dihydric phenol derivatives, like hydroquinone, 1,4‐naphthalenediol, 4,4’‐biphenol, and 1,1’‐bi‐2‐naphthol, or benzoic acid derivatives with hydroxy or amino group at the para position. Among 23 cocrystals found from 35 possible combinations of five ion‐pairs and seven hydrogen‐bond donors, 20 cocrystals were investigated by the X‐ray crystallographic analyses. Some of them also contained solvent molecules. In these cocrystals, hydrogen‐bond sequences composed of p‐toluenesulfonate and the hydrogen‐bond donors were observed, and ionic bonds between the first and second components and hydrogen bonds between the second and third components were found to be responsible for three‐π‐component cocrystals. When the cations were 4‐cyanopyridinium or quinolinium derivatives, the cocrystals showed charge‐transfer absorption bands due to electronic interaction between the cations and the hydrogen‐bond donors. To the mixture of quinolinium p‐toluenesulfonate and 1,1’‐bi‐2‐naphthol forming the three‐π‐component cocrystals, tetrathiafulvalene were added to form four‐π‐component cocrystals with ethanol or water molecules.

Correlating Structure with Spectroscopy in Ascorbate Peroxidase Compound II.

Structural and spectroscopic investigations of compound II in ascorbate peroxidase (APX) have yielded conflicting conclusions regarding the protonation state of the crucial Fe(IV) intermediate. Neutron diffraction and crystallographic data support an iron(IV)-hydroxo formulation, whereas Mössbauer, X-ray absorption (XAS), and nuclear resonance vibrational spectroscopy (NRVS) studies appear consistent with an iron(IV)-oxo species. Here we examine APX with spectroscopy-oriented QM/MM calculations and extensive exploration of the conformational space for both possible formulations of compound II. We establish that irrespective of variations in the orientation of a vicinal arginine residue and potential reorganization of proximal water molecules and hydrogen bonding, the Fe-O distances for the oxo and hydroxo forms consistently fall within distinct, narrow, and nonoverlapping ranges. The accuracy of geometric parameters is validated by coupled-cluster calculations with the domain-based local pair natural orbital approach, DLPNO-CCSD(T). QM/MM calculations of spectroscopic properties are conducted for all structural variants, encompassing Mössbauer, optical, X-ray absorption, and X-ray emission spectroscopies and NRVS. All spectroscopic observations can be assigned uniquely to an Fe(IV)═O form. A terminal hydroxy group cannot be reconciled with the spectroscopic data. Under no conditions can the Fe(IV)═O distance be sufficiently elongated to approach the crystallographically reported Fe-O distance. The latter is consistent only with a hydroxo species, either Fe(IV) or Fe(III). Our findings strongly support the Fe(IV)═O formulation of APX-II and highlight unresolved discrepancies in the nature of samples used across different experimental studies.

Cesium Carbonate Promoted Direct Amidation of Unactivated Esters with Amino Alcohol Derivatives.

Cesium carbonate promoted direct amidation of unactivated esters with amino alcohols was developed without the use of transition-metal catalysts and coupling reagents. This method enabled the synthesis of several serine-containing oligopeptides and benzamide derivatives with yields up to 90%. The methodology proceeds under mild reaction conditions and exhibits no racemization for most naturally occurring amino acid substrates. The reaction demonstrates good compatibility with primary alkyl and benzyl esters and broad tolerance for a range of amino acid substrates with nonpolar and protected side chains. The hydroxy group on the amine nucleophile was found to be critical for the reaction to be successful. A likely mechanism involving cesium coordination to the substrates enabling the subsequent proximity-driven acyl transfer was proposed. The practicality of this approach was demonstrated in the preparation of a biologically active nicotinamide derivative in a reasonable yield.

Acetylation of cotton knitted fabrics for improved quick drying after water absorption

Quick drying after water or sweat absorption is an important function of underwear. In this study, the hydroxy groups of cotton knitted fabrics (CFs) were partially acetylated, maintaining the original fabric structure. The following three heterogeneous acetylation processes were used: Ac-I (Ac2O/H2SO4/toluene), Ac-II (Ac2O/H2SO4/AcOH/water), and Ac-III (Ac2O/AcONa) systems (Ac2O, acetic anhydride; AcOH, acetic acid; AcONa, sodium acetate). Acetylated cotton knitted fabrics (AcCFs) with degree of substitution (DS) ≤ 0.5 and yields of > 80% were prepared. AcCFs prepared with the Ac-III system gave high degree of polymerization (DP) values of > 1500, whereas those prepared with the Ac-II system exhibited low DP values of ≤ 400. The moisture contents of AcCFs at 20 °C and 65% relative humidity decreased from 7.1 to 4.7% with increasing DS value up to 0.46; introducing hydrophobic acetyl groups into the CFs decreased their hydrophilic nature. Quick drying similar to that of a polyester fabric was achieved for some of the AcCFs with DS values of < 0.2. When the acetyl groups in the AcCFs were homogeneously distributed across each fiber width (achieved for AcCFs prepared with the Ac-II system), quick drying was evident in the AcCFs. The crystallinities and crystal widths of cellulose I for the AcCFs with DS values of ≤ 0.28 were almost unchanged compared with those of the original CFs. However, neither the crystallinities nor crystal widths of cellulose I were directly related to quick drying after water absorption. Thermal degradation of the AcCFs varied between the acetylation systems, and depended on the DP values and/or the presence of sulfate ester groups in the AcCFs.Graphical

Abstract 4491: Development of IRE-1 inhibitors for B cell cancer therapy

Abstract In response to the endoplasmic reticulum (ER) stress, the IRE-1 kinase/RNase splices the mRNA of the XBP-1 gene, resulting in the spliced XBP-1 (XBP-1s) mRNA that encodes the functional XBP-1s transcription factor. XBP-1s is critically important for the growth and survival of B cell leukemia, lymphoma, and multiple myeloma. When compared with other inhibitors targeting IRE-1, the tricyclic chromenone-based inhibitors B-I09 and D-F07, prodrugs harboring an aldehyde-masking group, emerged as the very reliable inhibitors for potent suppression of the XBP-1s protein. Protection of the aldehyde as a 1,3-dioxane acetal led to strong fluorescence emitted by the coumarin chromophore, enabling both B-I09 and D-F07 to be tracked inside the cell. We installed a photolabile structural cage on the hydroxy group of D-F07 to generate PC-D-F07. Such a modification significantly stabilized the 1,3-dioxane acetal protecting group, allowing for specific stimulus-mediated control of the inhibitory activity. Upon photoactivation, the re-exposed hydroxy group triggered the aldehyde-protecting 1,3-dioxane acetal to slowly decompose, leading to the inhibition of the RNase activity of IRE-1. Since chemical modifications of the hydroxy group could be used to tune 1,3-dioxane prodrug stability, we installed reactive oxygen species (ROS)-sensitive boronate cage groups onto B-I09 (BC-B-I09) and D-F07 (BC-D-F07) to achieve stimuli-responsive activities and improve tumor-targeting efficiency based on that cancerous B cells indeed produced higher levels of ROS than normal B cells. These boronate caged compounds could be further combined with the FDA-approved Auranofin, a thioredoxin reductase inhibitor, to achieve synergistic cancer-killing effects. These results led us to further develop a novel prodrug, TC-D-F07, in which a thiol-reactive dinitrobenzenesulfonyl (Dns) cage was installed onto the hydroxy group of D-F07. The electron-withdrawing Dns group in TC-D-F07 similarly stabilized the neighboring 1,3-dioxane acetal, allowing for stimulus-mediated control of its inhibitory activity. TC-D-F07 exhibited high sensitivity to intracellular thiols produced by cancerous B cells. In addition, when TC-D-F07 was decomposed into D-F07, we observed that a dinitrophenyl cysteine adduct resulting from cleavage of the Dns group could induce the ER stress, causing cancerous B cells to increase the expression of XBP-1s. However, the accumulated levels of D-F07 from TC-D-F07 and its gradual decomposition into the active IRE-1 inhibitor could eventually deprive cancer cells of all XBP-1s, leading to more severe apoptosis in TC-D-F07-treated than in D-F07-treated cells. Thus, TC-D-F07 with both ER stress-inducing and XBP-1s-inhibiting activities represents an IRE-1-targeting caged prodrug that can be used to treat B cell cancer effectively. Citation Format: Andong Shao, Chih-Hang Anthony Tang, Juan R. Del Valle, Chih-Chi Andrew Hu. Development of IRE-1 inhibitors for B cell cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4491.