Unlocking the Potential of Bi2S3-Derived Bi Nanoplates: Enhanced Catalytic Activity and Selectivity in Electrochemical and Photoelectrochemical CO2 Reduction to Formate.

Various electrocatalysts are extensively examined for their ability to selectively produce desired products by electrochemical CO2 reduction reaction (CO2RR). However, an efficient CO2RR electrocatalyst doesn't ensure an effective co-catalyst on the semiconductor surface for photoelectrochemical CO2RR. Herein, Bi2S3 nanorods are synthesized and electrochemically reduced to Bi nanoplates that adhere to the substrates for application in the electrochemical and photoelectrochemical CO2RR. Compared with commercial-Bi, the Bi2S3-derived Bi (S-Bi) nanoplates on carbon paper exhibit superior electrocatalytic activity and selectivity for formate (HCOO-) in the electrochemical CO2RR, achieving a Faradaic efficiency exceeding 93%, with minimal H2 production over a wide potential range. This highly selective S-Bi catalyst is being employed on the Si photocathode to investigate the behavior of electrocatalysts during photoelectrochemical CO2RR. The strong adhesion of the S-Bi nanoplates to the Si nanowire substrate and their unique catalytic properties afford exceptional activity and selectivity for HCOO- under simulated solar irradiation. The selectivity observed in electrochemical CO2RR using the S-Bi catalyst correlates with that seen in the photoelectrochemical CO2RR system. Combined pulsed potential methods and theoretical analyses reveal stabilization of the OCHO* intermediate on the S-Bi catalyst under specific conditions, which is critical for developing efficient catalysts for CO2-to-HCOO- conversion.

Methodology for Mapping the Residual Stress Field in Serviced Rails Using LCR Waves.

Non-destructive stress measurement by ultrasonic testing is based on calculating the acoustoelastic modulus obtained from the relationship between material stress and sound wave velocity. A critically refracted longitudinal (LCR) wave, which is a bulk longitudinal wave penetrating below and parallel to the surface below an effective depth, is most suitable for ultrasonic stress measurement tests because it exhibits a relatively large change in travel time in response to a change in stress. In particular, the residual stress distribution through the thickness of the subject can be calculated if transducers of different frequencies are applied because of the characteristic of propagation to different depths of penetration depending on the frequency. The main purpose of this study was to visualize the internal or residual stress distribution through the thickness of rails using LCR waves. To this end, LCR probes with different center frequencies were designed and manufactured, and the residual stress values ​​of an unused railroad rail and two used railroad rails operated under different conditions were calculated. This was done using the ultrasonic signals received from each probe, of which the distributions were mapped. Through these mapping results, different residual stress values could be calculated according to the depth. The differences in residual stress generation and distribution according to the conditions surrounding the contact between train wheels and rails, and their characteristics, were visualized and analyzed. As a result, it could be concluded that the non-destructive evaluation technique using LCR waves could detect differences in the residual stress of a rail, and thus can be used to measure the residual stress of the rail accurately.

Detoxification of Bee Venom Increases Its Anti-inflammatory Activity and Decreases Its Cytotoxicity and Allergenic Activity.

Bee venom is a medicinal product that is widely used in traditional therapies owing to its excellent anti-inflammatory activity. However, the use of bee venom has shown adverse effects. Therefore, there is a need for research that can remove the cytotoxicity of bee venom and enhance its efficacy. In this study, we hydrolyzed melittin, the main component of bee venom, and removed the other components to eliminate the toxicity of bee venom. To compare the efficacy of bee venom and detoxified bee venom, we examined their antioxidant effects using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. In addition, cytotoxicity was confirmed in MCF 10A and RAW 264.7 cells, using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Detoxified bee venom showed a strong antioxidant activity and decreased a cytotoxicity in MCF 10A and RAW 264.7 cells. The anti-inflammatory activity of detoxified bee venom and bee venom were assessed by comparison of the expression of inflammatory cytokine mRNA and phosphorylation of IκBα in RAW 264.7 cells. Degranulation in RBL-2H3 cells was analyzed through ß-hexosaminidase release assay to confirm the allergenic activity of bee venom and detoxified bee venom. Treatment of the detoxified bee venom inhibited inflammatory cytokine mRNA expression, IκBα phosphorylation, and ß-hexosaminidase release. Taken together, the results indicated that compared to bee venom, detoxified bee venom exhibited decreased cytotoxicity and allergenicity and increased anti-inflammatory activity. In conclusion, detoxification of bee venom efficiently decreases the adverse effects, making it suitable for medicinal applications.

A 26-GHz transmitter front-end using double quadrature architecture.

A 26-GHz transmitter front-end is designed using 65 nm CMOS technology. The double frequency conversion transmitter consists of an intermediate frequency(IF) mixer, an millimeter-wave(mm-wave) mixer, and a pre-power amplifier. A double quadrature architecture is employed to accomplish image rejection without using an image rejection filter for the first time in the mm-wave frequency band. The IF mixer cores are designed as harmonic rejection mixers to avoid using IF filters. The measured conversion gain is 26.85±0.65 dB, with LO2 (IF LO) at 1-1.5 GHz and 26.9±0.6 dB with LO1 (mm-wave LO) at 27-29 GHz. The measured output return loss is less than -10 dB at 25.7-27.2 GHz. The output 1-dB compression point and the saturation output power measured at 26 GHz are 10 dBm and 14.1 dBm, respectively. The output-referred third-order intercept point (OIP3) measured at 26 GHz is 15.76 dBm. The third-order distortion, suppressed by the harmonic rejection mixer, is -60.5 dBc at an output power of 10 dBm. The error vector magnitude measured for OFDM 16-QAM with a 110-MHz signal bandwidth is -17.7 dB at an average output power of 3.5 dBm. The total power consumption of the proposed 26-GHz transmitter front-end is 267 mW, and it occupies a chip area of 2.31 mm2.

An updated review on molecular mechanisms underlying the anticancer effects of capsaicin.

The quest for developing anticancer principles from natural sources has a long historical track record and remarkable success stories. The pungent principle of hot chili pepper, capsaicin, has been a subject of research for anticancer drug discovery for more than three decades. However, the majority of research has revealed that capsaicin interferes with various hallmarks of cancer, such as increased cell proliferation, evasion from apoptosis, inflammation, tumor angiogenesis and metastasis, and tumor immune escape. Moreover, the compound has been reported to inhibit carcinogen activation and chemically induced experimental tumor growth. Capsaicin has also been reported to inhibit the activation of various kinases and transcription that are involved in tumor promotion and progression. The compound activated mitochondria-dependent and death receptor-mediated tumor cell apoptosis. Considering the growing interest in capsaicin, this review provides an update on the molecular targets of capsaicin in modulating oncogenic signaling.

3-Deoxysappanchalcone Promotes Proliferation of Human Hair Follicle Dermal Papilla Cells and Hair Growth in C57BL/6 Mice by Modulating WNT/ß-Catenin and STAT Signaling.

3-Deoxysappanchalcone (3-DSC) has been reported to possess anti-allergic, antiviral, anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of 3-DSC on the proliferation of human hair follicle dermal papilla cells (HDPCs) and mouse hair growth in vivo. A real-time cell analyzer system, luciferase assay, Western blot and real-time polymerase chain reaction (PCR) were employed to measure the biochemical changes occurring in HDPCs in response to 3-DSC treatment. The effect of 3-DSC on hair growth in C57BL/6 mice was also examined. 3-DSC promoted the proliferation of HDPCs, similar to Tofacitinib, an inhibitor of janus-activated kinase (JAK). 3-DSC promoted phosphorylation of ß-catenin and transcriptional activation of the T-cell factor. In addition, 3-DSC potentiated interleukin-6 (IL-6)-induced phosphorylation and subsequent transactivation of signal transducer and activator of transcription-3 (STAT3), thereby increasing the expression of cyclin-dependent kinase-4 (Cdk4), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). On the contrary, 3-DSC attenuated STAT6 mRNA expression and IL4-induced STAT6 phosphorylation in HDPCs. Finally, we observed that topical application of 3-DSC promoted the anagen phase of hair growth in C57BL/6 mice. 3-DSC stimulates hair growth possibly by inducing proliferation of follicular dermal papilla cells via modulation of WNT/ß-catenin and STAT signaling.

Structural and photophysical properties of HPPCO (4-hydroxy-5-phenyl-6H-pyrido[3,2,1-jk]carbazol-6-one) derivatives.

Proton-substitution effects of 4-hydroxy-5-phenyl-6H-pyrido[3,2,1-jk]carbazol-6-one (HPPCO) on structural and photophysical properties were presented. HPPCO crystallized in the orthorhombic space group Pbca with an intermolecular hydrogen bonding between OH and oxygen atom of the carbonyl. The proton-substituted derivatives, 6-oxo-5-phenyl-6H-pyrido[3,2,1-jk]carbazol-4-yl acetate (OPPCA) and 6-oxo-5-phenyl-6H-pyrido[3,2,1-jk]carbazol-4-yl benzoate (OPPCB), crystallized in the monoclinic P21/c space group. For OPPCA and OPPCB, a weak interaction between carbonyl oxygen atom in the substituted group and carbon atom in the fused ring was responsible for three-dimensional arrangements. In addition, 6-oxo-5-phenyl-6H-pyrido[3,2,1-jk]carbazol-4-yl furan-2-carboxylate (OPPCF), and 6-oxo-5-phenyl-6H-pyrido[3,2,1-jk]carbazol-4-yl naphthoate (OPPCN) were also synthesized. HPPCO and the four derivatives excited by ultraviolet (UV) light produced blue emission. Proton substitution of the OH group significantly increased the radiative transitions and moderately decreased the non-radiative transitions. Consequently the luminescence quantum yields of the derivatives enhanced more than 4.6-fold, no matter what the groups were substituted. Structural and optical properties were further determined using density functional theory (DFT) and ZINDO calculations. The planar structure of the pyridocarbazole-fused ring resulted in π→π(*) electronic transitions within the main frame, with an additional transition from the n(O) of carbonyl to the π(*) of the main frame. The three excited states that arose from these transitions were responsible for the blue luminescence.

Substituted N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamides: potent anticonvulsants that affect frequency (use) dependence and slow inactivation of sodium channels.

We prepared 13 derivatives of N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamide that differed in type and placement of a R-substituent in the terminal aryl unit. We demonstrated that the R-substituent impacted the compound's whole animal and cellular pharmacological activities. In rodents, select compounds exhibited excellent anticonvulsant activities and protective indices (PI=TD50/ED50) that compared favorably with clinical antiseizure drugs. Compounds with a polar, aprotic R-substituent potently promoted Na+ channel slow inactivation and displayed frequency (use) inhibition of Na+ currents at low micromolar concentrations. The possible advantage of affecting these two pathways to decrease neurological hyperexcitability is discussed.

Capillary force-induced glue-free printing of Ag nanoparticle arrays for highly sensitive SERS substrates.

The fabrication of well-ordered metal nanoparticle structures onto a desired substrate can be effectively applied to several applications. In this work, well-ordered Ag nanoparticle line arrays were printed on the desired substrate without the use of glue materials. The success of the method relies on the assembly of Ag nanoparticles on the anisotropic buckling templates and a special transfer process where a small amount of water rather than glue materials is employed. The anisotropic buckling templates can be made to have various wavelengths by changing the degree of prestrain in the fabrication step. Ag nanoparticles assembled in the trough of the templates via dip coating were successfully transferred to a flat substrate which has hydrophilic surface due to capillary forces of water. The widths of the fabricated Ag nanoparticle line arrays were modulated according to the wavelengths of the templates. As a potential application, the Ag nanoparticle line arrays were used as SERS substrates for various probing molecules, and an excellent surface-enhanced Raman spectroscopy (SERS) performance was achieved with a detection limit of 10(-12) M for Rhodamine 6G.

Benzyloxybenzylammonium chlorides: Simple amine salts that display anticonvulsant activity.

Several antiepileptic drugs exert their activities by inhibiting Na(+) currents. Recent studies demonstrated that compounds containing a biaryl-linked motif (Ar-X-Ar') modulate Na(+) currents. We, and others, have reported that compounds with an embedded benzyloxyphenyl unit (ArOCH2Ar', OCH2=X) exhibit potent anticonvulsant activities. Here, we show that benzyloxybenzylammonium chlorides ((+)H3NCH2C6H4OCH2Ar' Cl(-)) displayed notable activities in animal seizure models. Electrophysiological studies of 4-(2'-trifluoromethoxybenzyloxy)benzylammonium chloride (9) using embryonic cortical neurons demonstrated that 9 promoted both fast and slow inactivation of Na(+) channels. These findings suggest that the potent anticonvulsant activities of the earlier compounds were due, in part, to the benzyloxyphenyl motif and provide support for the use of the biaryl-linked pharmacophore in future drug design efforts.

(Biphenyl-4-yl)methylammonium chlorides: potent anticonvulsants that modulate Na+ currents.

We have reported that compounds containing a biaryl linked unit (Ar-X-Ar') modulated Na(+) currents by promoting slow inactivation and fast inactivation processes and by inducing frequency (use)-dependent inhibition of Na(+) currents. These electrophysiological properties have been associated with the mode of action of several antiepileptic drugs. In this study, we demonstrate that the readily accessible (biphenyl-4-yl)methylammonium chlorides (compound class B) exhibited a broad range of anticonvulsant activities in animal models, and in the maximal electroshock seizure test the activity of (3'-trifluoromethoxybiphenyl-4-yl)methylammonium chloride (8) exceeded that of phenobarbital and phenytoin upon oral administration to rats. Electrophysiological studies of 8 using mouse catecholamine A-differentiated cells and rat embryonic cortical neurons confirmed that 8 promoted slow and fast inactivation in both cell types but did not affect the frequency (use)-dependent block of Na(+) currents.

Massive lumbar disc herniation with complete dural sac stenosis.

BACKGROUND: Large lumbar disc herniation (LDH) has been reported to have a greater tendency to resolve in clinical and pathomorphological evolutions. However, various definitions of large LDH have been used without validation, and the clinical symptoms of large LDH have not been fully elucidated. We conducted a retrospective analysis to determine the clinical characteristics and treatment outcome of massive LDH with complete dural sac stenosis. MATERIALS AND METHODS: We retrospectively reviewed 33 cases of LDH with complete dural sac stenosis on magnetic resonance imaging. Complete dural sac stenosis was defined as no recognizable rootlet and cerebrospinal fluid signal on T2-weighed axial MR images. The clinical outcome parameters included back pain, leg pain, Oswestry disability index (ODI), and neurological dysfunction. The paired t-test and Wilcoxon's signed rank test were used to compare serial changes in back pain, leg pain and neurological dysfunction. RESULTS: Mean duration of followup was 66 months (range 24 - 108 months). There were 24 male and 9 female. The mean age was 37 years (range 20 - 53 years). At presentation, mean visual analogue scales for back pain and leg pain were 75.3 ± 19.1 (range 12 - 100) and 80.2 ± 14.6 (range 0 -100), respectively. Mean ODI was 67.1 ± 18.8 (range 26 - 88). Neurological dysfunction was found in 9 patients (27.3%), and the bowel/bladder dysfunction was found in 2 patients (3.1%). Conservative treatment was performed in 21 patients (63.6%) with satisfactory results. Seven patients underwent decompressive surgery, and 5 underwent posterolateral fusion. CONCLUSIONS: A massive LDH with complete dural sac stenosis was found to be associated with severe back and leg pain at presentation, however surgical treatment can be deferred unless significant neurological symptoms occur.

Discovery of lacosamide affinity bait agents that exhibit potent voltage-gated sodium channel blocking properties.

Lacosamide ((R)-1) is a recently marketed, first-in-class, antiepileptic drug. Patch-clamp electrophysiology studies are consistent with the notion that (R)-1 modulates voltage-gated Na(+) channel function by increasing and stabilizing the slow inactivation state without affecting fast inactivation. The molecular pathway(s) that regulate slow inactivation are poorly understood. Affinity baits are chemical reactive units, which when appended to a ligand (drug) can lead to irreversible, covalent modification of the receptor thus permitting drug binding site identification including, possibly, the site of ligand function. We describe, herein, the synthesis of four (R)-1 affinity baits, (R)-N-(4″-isothiocyanatobiphenyl-4'-yl)methyl 2-acetamido-3-methoxypropionamide ((R)-8), (S)-N-(4″-isothiocyanatobiphenyl-4'-yl)methyl 2-acetamido-3-methoxypropionamide ((S)-8), (R)-N-(3″-isothiocyanatobiphenyl-4'-yl)methyl 2-acetamido-3-methoxypropionamide ((R)-9), and (R)-N-(3″-acrylamidobiphenyl-4'-yl)methyl 2-acetamido-3-methoxypropionamide ((R)-10). The affinity bait compounds were designed to interact with the receptor(s) responsible for (R)-1-mediated slow inactivation. We show that (R)-8 and (R)-9 are potent inhibitors of Na(+) channel function and function by a pathway similar to that observed for (R)-1. We further demonstrate that (R)-8 function is stereospecific. The calculated IC50 values determined for Na(+) channel slow inactivation for (R)-1, (R)-8, and (R)-9 were 85.1, 0.1, and 0.2 µM, respectively. Incubating (R)-9 with the neuronal-like CAD cells led to appreciable levels of Na(+) channel slow inactivation after cellular wash, and the level of slow inactivation only modestly decreased with further incubation and washing. Collectively, these findings have identified a promising structural template to investigate the voltage-gated Na(+) channel slow inactivation process.

Development of novel CH223191-based antagonists of the aryl hydrocarbon receptor.

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates genes involved in drug/xenobiotic metabolism, cell cycle progression, cell fate determination, immune function, and inflammatory response. Increasing evidence that AHR plays a role in the pathophysiology of a number of human disease states is driving the need for improved pharmacological tools to be used for understanding the in vivo impact of AHR modulation. In this study, we have characterized and used structure-activity relationship analyses of a newly synthesized library of derivatives of the potent AHR antagonist 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH223191). Initial screening of these compounds revealed that those bearing groups with strong electronegativity at the R1 position (i.e., CHD-5, CHD-11, and CHD-12) versus those that are more electron-poor at this position (i.e., CHD-7 and CHD-8) elicited the most potent AHR antagonistic properties. The ability of these derivatives to inhibit agonist (2,3,7,8-tetrachlorodibenzo-p-dioxin) binding, nuclear translocation of AHR, and agonist-induced enzyme activity also were determined and support the initial findings. Furthermore, CH223191, but not CHD-5, CHD-11, or CHD-12, was found to exhibit AHR-independent proproliferative properties. These results contribute to our understanding of the structural requirements of potent AHR antagonists and the development of effective pharmacological tools to be used for studying the pathophysiological role of AHR.

Luminescence properties of 4-hydroxy-5-phenylpyrido[3,2,1-jk]carbazol-6-one: solvatochromism and sensitivity to amine solution.

A detailed photophysical analysis of 4-hydroxy-5-phenylpyrido[3,2,1-jk]carbazol-6-one (HPPCO) is presented. When exposed to UV light, the compound produced deep blue to green luminescence, depending on the solvent. The luminescence peak shifts with the Gutmann donor number (DN) of the solvent and the proton substitution affects luminescence; a correlation between quantum yield and decay time indicated that proton transfer plays a key role in the observed solvatochromism. The ground-state deprotonation of HPPCO was apparently evidenced from the absorption and/or the excitation spectra in the solvents with large DN values. DFT and ZINDO calculations on the structural and optical properties have shown that deprotonation increases the contribution of oxygen atoms to the HOMO, thereby lowering the transition energy from the HOMO to the LUMO. Because the luminescence properties of HPPCO depend on proton transfer, it may be used to detect and quantitate amines in solution. The sensitivity of the luminescence to various amines was ∼10(5) M(-1) and was more effective in ethanol than in methanol.

Impact of linker length on the activity of PROTACs.

Conventional genetic approaches have provided a powerful tool in the study of proteins. However, these techniques often preclude selective manipulation of temporal and spatial protein functions, which is crucial for the investigation of dynamic cellular processes. To overcome these limitations, a small molecule-based novel technology termed "PROteolysis TArgeting ChimeraS (PROTACs)" has been developed, targeting proteins for degradation at the post-translational level. Despite the promising potential of PROTACs to serve as molecular probes of complex signaling pathways, their design has not been generalized for broad application. Here, we present the first generalized approach for PROTAC design by fine-tuning the distance between the two participating partner proteins, the E3 ubiquitin ligase and the target protein. As such, we took a chemical approach to create estrogen receptor (ER)-α targeting PROTACs with varying linker lengths and the loss of the ER in cultured cells was monitored via western blot and fluorometric analyses. We found a significant effect of chain length on PROTAC efficacy, and, in this case, the optimum distance between the E3 recognition motif and the ligand was a 16 atom chain length. The information gathered from this experiment may offer a generalizable PROTAC design strategy to further the expansion of the PROTAC toolbox, opening new possibilities for the broad application of the PROTAC strategy in the study of multiple signaling pathways.

Jostling for position: optimizing linker location in the design of estrogen receptor-targeting PROTACs.

Estrogen receptor-alpha (ER) antagonists have been widely used for breast cancer therapy. Despite initial responsiveness, hormone-sensitive ER-positive cancer cells eventually develop resistance to ER antagonists. It has been shown that in most of these resistant tumor cells, the ER is expressed and continues to regulate tumor growth. Recent studies indicate that tamoxifen initially acts as an antagonist, but later functions as an ER agonist, promoting tumor growth. This suggests that targeted ER degradation may provide an effective therapeutic approach for breast cancers, even those that are resistant to conventional therapies. With this in mind, we previously demonstrated that proteolysis targeting chimeras (PROTACs) effectively induce degradation of the ER as a proof-of-concept experiment. Herein we further refined the PROTAC approach to target the ER for degradation. The ER-targeting PROTACs are composed of an estradiol on one end and a hypoxia-inducing factor 1alpha (HIF-1alpha)-derived synthetic pentapeptide on the other. The pentapeptide is recognized by an E3 ubiquitin ligase called the von Hippel Lindau tumor suppressor protein (pVHL), thereby recruiting the ER to this E3 ligase for ubiquitination and degradation. Specifically, the pentapeptide is attached at three different locations on estradiol to generate three different PROTAC types. With the pentapeptide linked through the C7alpha position of estradiol, the resulting PROTAC shows the most effective ER degradation and highest affinity for the estrogen receptor. This result provides an opportunity to develop a novel type of ER antagonist that may overcome the resistance of breast tumors to conventional drugs such as tamoxifen and fulvestrant (Faslodex).

Inflexinol inhibits colon cancer cell growth through inhibition of nuclear factor-kappaB activity via direct interaction with p50.

Kaurane diterpene compounds have been known to be cytotoxic against several cancer cells through inhibition of nuclear factor-kappaB (NF-kappaB) activity. Here, we showed that inflexinol, a novel kaurane diterpene compound, inhibited the activity of NF-kappaB and its target gene expression as well as cancer cell growth through induction of apoptotic cell death in vitro and in vivo. These inhibitory effects on NF-kappaB activity and on cancer cell growth were suppressed by the reducing agents DTT and glutathione and were abrogated in the cells transfected with mutant p50 (C62S). Sol-gel biochip and surface plasmon resonance analysis showed that inflexinol binds to the p50 subunit of NF-kappaB. These results suggest that inflexinol inhibits colon cancer cell growth via induction of apoptotic cell death through inactivation of NF-kappaB by a direct modification of cysteine residue in the p50 subunit of NF-kappaB.

Development of an aryl hydrocarbon receptor antagonist using the proteolysis-targeting chimeric molecules approach: a potential tool for chemoprevention.

Activation of the aryl hydrocarbon receptor (AHR) by agonists and environmental contaminants like dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) leads to many adverse biological effects, including tumor promotion. With this in mind, we propose that agents that block the AHR pathway may be therapeutically beneficial, particularly by exhibiting chemopreventive activities. In our current research, we have focused on the development of an AHR antagonist using a chemical genetic approach called PROTACS (PROteolysis-TArgeting Chimeric moleculeS). PROTACS is a novel approach of tagging small recognition sequences of a specific E3 ubiquitin ligase complex to a known ligand for the receptor of interest (AHR) for targeting its degradation. Here, we present the design and initial characterization of AHR targeting PROTACS (Apigenin-Protac) designed to degrade and inhibit the AHR in epithelial cells. Our results demonstrate the "proof of concept" of this approach in effectively blocking AHR activity in cultured cells.