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Rearranged during transfection (RET), an oncogenic driver, has been found in multiple tumor types and is thus a promising anticancer therapeutic target. Novel selective RET inhibitors (RETi) that can overcome V804 gatekeeper mutations, endowing resistance to multikinase inhibitors (MKI) and, in particular, achieving KDR selectivity, are needed. In addition, the mechanisms underlying RET–inhibition-induced antiproliferative effects in the context of RET addiction are incompletely understood. This study describes a novel selective RETi, SYHA1815, which inhibited the kinase activity of RET wild type and V804 mutant with an IC50 in the subnanomolar to nanomolar range. Notably, SYHA1815 exhibited approximately 20-fold selectivity for RET over KDR, almost equivalent to that of the launched selective inhibitor pralsetinib. SYHA1815 had only a marginal inhibitory effect on cellular KDR signaling at a high (200 nmol/L) concentration, confirming the selectivity over KDR. In addition, SYHA1815 exhibited a favorable selectivity profile, with greater than 100-fold selectivity for RET over 347 other kinases. It exhibited potent antitumor efficacy and overcame V804 mutations in vitro and in vivo by targeting RET. Then, using SYHA1815 as a probe, we found that RET inhibition suppressed RET-driven cell proliferation via G1 cell-cycle arrest through downregulating c-Myc. Furthermore, disruption of c-Myc upon Brd4 inhibitor treatment led to G1 cell-cycle arrest and overrode RET-driven cell proliferation. Moreover, consistent with the marked in vivo efficacy of RET inhibition, the intratumoral c-Myc level was significantly decreased. In summary, SYHA1815 is a promising RETi for RET-aberrant cancer treatment that is currently in a phase I trial.

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The CO2 conversion into high-value-added chemicals is highly meaningful.

Rearranged during transfection (RET), an oncogenic driver, has been found in multiple tumor types and is thus a promising anticancer therapeutic target. Novel selective RET inhibitors (RETi) that can overcome V804 gatekeeper mutations, endowing resistance to multikinase inhibitors (MKI) and, in particular, achieving KDR selectivity, are needed. In addition, the mechanisms underlying RET–inhibition-induced antiproliferative effects in the context of RET addiction are incompletely understood. This study describes a novel selective RETi, SYHA1815, which inhibited the kinase activity of RET wild type and V804 mutant with an IC50 in the subnanomolar to nanomolar range. Notably, SYHA1815 exhibited approximately 20-fold selectivity for RET over KDR, almost equivalent to that of the launched selective inhibitor pralsetinib. SYHA1815 had only a marginal inhibitory effect on cellular KDR signaling at a high (200 nmol/L) concentration, confirming the selectivity over KDR. In addition, SYHA1815 exhibited a favorable selectivity profile, with greater than 100-fold selectivity for RET over 347 other kinases. It exhibited potent antitumor efficacy and overcame V804 mutations in vitro and in vivo by targeting RET. Then, using SYHA1815 as a probe, we found that RET inhibition suppressed RET-driven cell proliferation via G1 cell-cycle arrest through downregulating c-Myc. Furthermore, disruption of c-Myc upon Brd4 inhibitor treatment led to G1 cell-cycle arrest and overrode RET-driven cell proliferation. Moreover, consistent with the marked in vivo efficacy of RET inhibition, the intratumoral c-Myc level was significantly decreased. In summary, SYHA1815 is a promising RETi for RET-aberrant cancer treatment that is currently in a phase I trial.

In this work, solar-heating-induced temperature-based photocatalytic hydrogen evolution reaction (PC-HER) of different photocatalysts (TiO2 P25, g-C3N4, and their loaded Pt) was comprehensively stu...

Photocatalytic process represents a promising approach to overcome the pollution challenge associated with the antibiotics-containing wastewater. This study provides a green, efficient and novel approach to remove cephalosporins, particularly cefoperazone sodium (CFP). Bi4O5Br2 was chosen for the first time to systematically study its degradation for CFP, including the analysis of material structure, degradation performance, the structure and toxicity of the transformation products, etc. The degradation rate results indicated that Bi4O5Br2 had an excellent catalytic activity leading to 78% CFP removal compared with the pure BiOBr (38%) within 120 min of visible light irradiation. In addition, the Bi4O5Br2 presents high stability and good organic carbon removal efficiency. The effects of the solution pH (3.12 - 8.75) on catalytic activity revealed that CFP was mainly photocatalyzed under acidic conditions and hydrolyzed under alkaline conditions. Combined with active species and degradation product identification, the photocatalytic degradation pathways of CFP by Bi4O5Br2 was proposed, including hydrolysis, oxidation, reduction and decarboxylation. Most importantly, the identified products were all hydrolysis rather than oxidation byproducts transformed from the intermediate of β-lactam bond cleavage in CFP molecule, quite different from the mostly previous studies. Furthermore, the final products were demonstrated to be less toxic through the toxicity analysis. Overall, this study illustrates the detailed mechanism of CFP degradation by Bi4O5Br2 and confirms Bi4O5Br2 to be a promising material for the photodegradation of CFP.

Surface fluorinated TiO2 has received extensive attention in recent years due to the improved photocatalytic reactivity compared with that of pure TiO2. However, the synergy of surface fluorine (FS) and oxygen vacancy (VO) is not clear and needs further study. Here we systematically studied the effect of FS, VO and acidic sites of TiO2 nanosheets on the selective photocatalytic oxidation of benzylamine to imine. The photocatalytic activity first increased and then decreased as the content of FS decreased and VO increased. The photocatalytic activity reached a summit with the imine yield of 92.1% over TiO2-B-6 h, which is mainly due to the synergy between FS and adjacent VO, forming the frustrated Lewis pair that boosts the activation of O2. The varied contents of FS and VO not only cause an evident change in the amount of acidic sites, but also affect the band structure and separation efficiency of charge carriers. The experimental and calculation results demonstrate that the coexistence of FS and VO boosted the separation efficiency, density and mobility of photogenerated charge carriers, resulting in the improved photocatalytic activity. The improved photocatalytic activity can be attributed to the combined effects of FS, VO and acidic sites. This work provides a strategy for the explicit regulation of surface species on TiO2 nanosheets for improved photocatalytic activity.

In this work, BiVO4 composites, containing the tetragonal zircon phase (tz-BiVO4), and monoclinic scheelite phase (ms-BiVO4), were synthesized using the microemulsion method. The effect of pH on phase composition and photocatalytic activity were investigated. Based on X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), a ms/tz-BiVO4 composite forms at pH = 1.0 and pure ms-BiVO4 is obtained in the pH range 4.0–10.0. The three primary steps in preparing BiVO4 were monitored by optical microscopy and the role played by the microemulsion on the phase composition of BiVO4 is explained. Photoluminescence spectroscopy (PL), UV–visible diffuse reflectance spectroscopy (UV-DRS), Brunauer-Emmett-Teller (BET), linear sweep voltammetry (LSV) and electrochemical impedance spectroscopy (EIS) were employed to characterize the physical and chemical properties of BiVO4 composites. The composite formed at pH = 1 exhibited the lowest hole-electron (h+-e-) recombination rate, resulting in the highest photocatalytic activity towards microcystin-LR (MC-LR), with near 100% removal of MC-LR in 5 h. ESR and trapping experiments indicated that MC-LR degradation was mediated primarily by hydroxyl radicals (•OH), superoxide radicals (O2•−) and photogenerated holes (h+).

TY-011, a novel Aurora A/B kinases inhibitor, was found in our previous study to exhibit prominent inhibitory effects on growth of gastric cancer, both in vitro and in vivo. To clarify the mechanisms of TY-011 in inhibiting proliferation of gastric cancer cells, the effects of TY-011 on mitosis, cell cycle, apoptosis and cellular DNA were checked in the present study. Our results showed that TY-011 treatment induced aberrant mitosis, G2/M phase arrest and apoptosis. Importantly, TY-011 induced evident DNA damage in MGC-803 and MKN-45 human gastric cancer cells, which was further characterized as DNA double-strand break. Furthermore, cells treated with TY-011 appeared to generate multiple spindle fibers emanating from several spindle poles, leading to poly-merotelic kinetochore. These results suggested that TY-011 induced abnormal microtubule-kinetochores attachment and thus DNA damage, apoptosis and finally inhibition of cell proliferation of human gastric cancer cells.

Herein, a series of HSP90 inhibitor-SN38 conjugates through ester and carbamate linkage in the 20-OH and 10-OH positions of SN38 were developed for improving the tumor-specific penetration and accumulation of SN38 via extracellular HSP90 (eHSP90)-mediated endocytosis. Mechanistic analyses confirmed that these novel conjugates could bind to eHSP90 and be selectively internalized into the tumor cells, which led to prolonged tumor regression in multiple models of cancer. Among all studied conjugates, compound 18b showed excellent in vitro activities, including acceptable HSP90α affinity and potent antitumor activity. Moreover, compound 18b exhibited superior antitumor activity and low toxicity in HCT116 and Capan-1 xenograft models. Pharmacokinetic analyses in HCT116 and Capan-1 xenografts further confirmed that compound 18b treatment could lead to effective cleavage and extended SN38 exposure at tumor sites. All these encouraging data indicate that this compound is a promising new candidate for cancer therapy and merits further chemical and biological evaluation.

Eutrophication of water bodies is a phenomenon during which toxic microcystins from cyanobacteria are released into water. Natural minerals in soils and sediments are able to catalyze the degradation of microcystins. Here we studied the hydrolytic removal of microcystins on the surface of pyrite (FeS2). The surface structure of pyrite was analyzed by X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy and Fourier transformed infrared. The surface acidity of pyrite was measured by in situ diffuse reflectance infrared Fourier transform spectroscopy during pyridine adsorption/desorption. The concentration of d-alanine, d-glutamic acid, l-arginine and l-leucine were determined in pyrite/microcystin aqueous solution by high-performance liquid chromatography. Hydrolysis at the pyrite–microcystin interface was monitored by attenuated total reflection Fourier transformed infrared spectroscopy. Results show that sulfion and iron are layered, wherein the sulfion is above the surface, which provides active sites for the hydrolysis of microcystins. The hydrolysis rate of microcystins was up to 100% at 60 °C after 24 h in the presence of pyrite, based on the yield of l-arginine. Surface Lewis (≡Fe) and Bronsted acid (≡SH) sites of pyrite possibly bond to the carbonyl oxygen of peptide bonds, leading to highly efficient hydrolysis of microcystins.

There are increasing concerns about detoxification of microcystin-LR (MC-LR) over the past few decades. Nevertheless, the removal of MC-LR in water by hydrolysis has not been addressed yet. The hydrolysis efficiencies of MC-LR by six natural minerals were investigated in the present study. Limonite displayed the highest activity among the screened six minerals, which is in accordance with the highest specific surface area (17.8 m2/g) and surface acidity. The hydrolysis of MC-LR was catalyzed by Lewis acid sites on limonite surface. The effects of temperature, pH reaction time and illumination on MC-LR hydrolysis catalyzed by limonite were then investigated. As expected, the high temperature, the addition of either acid or base and long reaction time could enhance the reaction rate, but UV light irradiation had little influence. These results give the indication that naturally occurring minerals can promote the hydrolysis of MC-LR, which gives a more universal view about the natural degradation of microcystins and could lead to more accurate predictions of the duration of microcystin toxicity in environment.

Microcystin-LR (MC-LR), which is produced from cyanobacteria, is the common microcystin with a serious threat to aquatic life and human beings. And the efficient removal method of MC-LR is urgent needed. In this work, the MIL-100/MIL-53 (Fe) photocatalysts, which were successfully prepared by the electrostatic interaction with each other, were applied for the photocatalytic degradation of MC-LR. The structure and optical properties of the MIL-100/MIL-53 (Fe) photocatalysts were characterized by using SEM, XRD, XPS, FT-IR and UV–vis DRS. The very low dosage of the MIL-100/MIL-53 (Fe) photocatalysts achieved the degradation of MC-LR, and the optimized loading was the 50% MIL-100/MIL-53 (Fe) photocatalyst. Compared to MIL-100 (Fe) and MIL-53 (Fe), the MC-LR degradation was up to 96.5% after 3 h under visible light illumination with the 50% MIL-100/MIL-53 (Fe) photocatalyst due to the pore-effect adsorption and the effective separation of photogenerated carriers. The effect of coordinate immobilized layers between MIL-100 (Fe) and MIL-53 (Fe) contributed to the stable and efficient removal of MC-LR for the 50% MIL-100/MIL-53 (Fe) photocatalyst. The MC-LR photocatalytic mechanism and degradation pathway, which the photogenerated holes (h+) were the main active species, were proposed by radical capture experiments and LC-MS analysis.

In this paper, bismuth oxybromide (BiOBr) photocatalysts were synthesized in the presence of tetrabutylammonium bromide (TBAB) at the different volume fractions of ethanol/water and named as BiOBr0, BiOBr20, BiOBr50, BiOBr80 and BiOBr100, respectively. The samples were characterized and applied to the degradation of Rhodamine B (RhB) under visible-light irradiation (λ ≥ 420 nm). The results indicated that both TBAB and ethanol significantly affected the crystal phase, morphology and surface charge distribution of BiOBr. The exposed (110) faces of BiOBr with Bi3+ sites contributed to its photocatalytic activity via the enhanced separation of electrons and photogenerated holes as well as the better photo-stability. BiOBr50 showed the optimal activity for the photodegradation of RhB. Superoxide radical (O2·−) as the dominant active species was responsible for the degradation of RhB.

Solar-driven advanced oxidation processes (AOPs) via direct photodegradation or indirect photocatalytic activation of typical oxidants, such as hydrogen peroxide (H

With the development of chip test technology, high speed IO test gradually convert from at speed test to abist test. ATE needs to configure thousands of registers by d2s during abist test, which brings low debug efficiency and the risk that the amount of generated pattern exceed the 93K upper limit. This paper proposes a new register configuration solution which generate the pattern in offline mode instead of traditional way. Meanwhile, this paper designs a software tool to generate the pattern in offline mode. In this tool, the registers data and address information will be parsed, and the JTAG protocol frame format constructed based on the information provided by the user. The pattern generator will create the main pattern, burst pattern and pattern master file based on the constructed data structure and protocol frame format. A new pattern generation mode was developed namely multi-write or multi-read. A big main pattern will be created instead of a series of small pattern of one suite in the new mode. The actual result shows that the debug efficiency improves 86.6%, the pattern number reduce 40%, and the pattern execution efficiency improve 69%.

This study presents a new bottom-up biofabrication method to produce highly porous magnetic biochar from waste-derived fungal biomass. Neurospora crassa was grown in iron containing coagulation backwash (BW) diluted with primary effluent (PE) wastewater in two ratios of 1:4 (PE-BW 1:4) and 3:4 (PE-BW 3:4). The fungi encapsulated iron directly into biomass hyphae and carbonization resulted in one-step biochar preparation and maghemite (Fe2O3) formation. The morphology and structure of the materials were investigated using a suite of characterization tools. Results indicated that the physiochemical properties of each char were dependent on the blend used for fungal cultivation. PE-BW 1:4 had much larger average pore diameters (13.2 nm vs. 6.1 nm), less elemental surface carbon (2.1% vs. 23.7%), and more expansive Fe2O3 formation. Batch phosphorus adsorption experiments were conducted in the range of 0–90 mg-P/L, and a maximum adsorption density of 23.9 mg/g was achieved. Langmuir, Freundlich and Temkin isotherms were used to describe the interactions of the phosphate on the absorbents and an in-depth error analysis was conducted. Further characterization of the P-loaded chars indicated adsorption primarily via P-OH bonding on the surface of the materials. This new biofabrication method showed great potential to magnetic biochar production with excellent phosphorus adsorption, which can be effectively used in wastewater resource recovery.

Deregulated Polycomb repressive complex 2 (PRC2) is intimately involved in tumorigenesis and progression, making it an invaluable target for epigenetic cancer therapy. Disrupting the EZH2-EED interaction, which is required for PRC2 enzymatic activity, is a promising strategy for cancer treatment. However, this kind of inhibitors are still limited. The in-cell protein-protein interaction screening was conducted for approximately 1300 compounds by NanoBRET technology. Co-immunoprecipitation (Co-IP), protein thermal shift assay (PTSA), and cellular thermal shift assay (CETSA) were performed to investigate the regulation of PRC2 by AZD9291. The anti-tumor effects of AZD9291 on breast cancer (BC) cells and diffuse large B-cell lymphoma (DLBCL) cells were detected. MicroRNA array assay, luciferase reporter assay, and qRT-PCR were conducted to identify the interaction and regulation among AZD9291, EZH2, and miR-34a. We discovered that, AZD9291, a potent and selective EGFR inhibitor, disrupted the interaction of EZH2-EED, leading to impairment of PRC2 activity and downregulation of EZH2 protein. In addition, AZD9291 declined EZH2 mRNA expression via upregulating the expression of a tumor suppressor, miR-34a. Our results suggest that AZD9291 can serve as a lead compound for further development of antagonist of PRC2 protein-protein interactions and EZH2 mRNA may be a direct target of miR-34a through non-canonical base pairing.

Rearranged during transfection (RET), an oncogenic driver, has been found in multiple tumor types and is thus a promising anticancer therapeutic target. Novel selective RET inhibitors (RETi) that can overcome V804 gatekeeper mutations, endowing resistance to multikinase inhibitors (MKI) and, in particular, achieving KDR selectivity, are needed. In addition, the mechanisms underlying RET-inhibition-induced antiproliferative effects in the context of RET addiction are incompletely understood. This study describes a novel selective RETi, SYHA1815, which inhibited the kinase activity of RET wild type and V804 mutant with an IC

The increasing presence of glyphosate has raised concerns about its potential impact on the environment and human health. The oxidative degradation of glyphosate during biotic and abiotic pathways usually leads to the formation of the toxic and persistent intermediates aminomethylphosphonic acid (AMPA). In this work, we report that the formation of AMPA during the photocatalytic degradation of glyphosate can be determined by its adsorption modes on the photocatalyst. The maximum accumulation of AMPA reached 31% on TiO2 photocatalyst. However, the formation of AMPA was markedly suppressed in the presence of F– ions, while the production of inorganic species such as PO43– and NO3– was largely enhanced. In situ attenuated total reflectance Fourier transforms infrared (ATR-FTIR) spectroscopy revealed that the glyphosate was adsorbed on surface of TiO2 by its phosphate and carboxylate groups, while the adsorption site was changed to its amine group in the presence of F– ions. Such a change in the adsorption mode of glyphosate would facilitate the C–N bonds cleavage in glyphosate molecules, and inhibit the formation of AMPA, which makes the degradation of glyphosate go along a less toxic degradation pathway. The present study reveals a new relationship between the degradation pathway and the adsorption mode of glyphosate, which may also be helpful in other systems of abiotic degradation of glyphosate.

The ROS1 fusion kinase is an attractive antitumor target. Though with significant clinical efficacy, the well-known first-generation ROS1 inhibitor (ROS1i) crizotinib inevitably developed acquired resistance due to secondary point mutations in the ROS1 kinase. Novel ROS1is effective against mutations conferring secondary crizotinib resistance, especially G2032R, are urgently needed. In the present study, we evaluated the antitumor efficacy of SAF-189s, the new-generation ROS1/ALK inhibitor, against ROS1 fusion wild-type and crizotinib-resistant mutants. We showed that SAF-189s potently inhibited ROS1 kinase and its known acquired clinically resistant mutants, including the highly resistant G2032R mutant. SAF-189s displayed subnanomolar to nanomolar IC(50) values against ROS1 wild-type and mutant kinase activity and a selectivity vs. other 288 protein kinases tested. SAF-189s blocked cellular ROS1 signaling, and in turn potently inhibited the cell proliferation in HCC78 cells and BaF3 cells expressing ROS1 fusion wild-type and resistance mutants. In nude mice bearing BaF3/CD74–ROS1 or BaF3/CD74–ROS1(G2032R) xenografts, oral administration of SAF-189s dose dependently suppressed the growth of both ROS1 wild-type- and G2032R mutant-driven tumors. In a patient-derived xenograft model of SDC4–ROS1 fusion NSCLC, oral administration of SAF-189s (20 mg/kg every day) induced tumor regression and exhibited notable prolonged and durable efficacy. In addition, SAF-189s was more potent than crizotinib and comparable to lorlatinib, the most advanced ROS1i known against the ROS1(G2032R). Collectively, these results suggest the promising potential of SAF-189s for the treatment of patients with the ROS1 fusion G2032R mutation who relapse on crizotinib. It is now recruiting both crizotinib-relapsed and naive ROS1-positive NSCLC patients in a multicenter phase II trial (ClinicalTrials.gov Identifier: NCT04237805).

Photocatalytic process represents a promising approach to overcome the pollution challenge associated with the antibiotics-containing wastewater. This study provides a green, efficient and novel approach to remove cephalosporins, particularly cefoperazone sodium (CFP). Bi

A series of BiVO

The mechanisms of how Never in Mitosis (NIMA) Related Kinase 2 (NEK2) coordinates altered signaling to malignant gastric cancer (GC) transformation remain unclear. Overexpression of NEK2 and KDM5B were observed in GC cell lines with high sensitivity to NEK2 inhibitors. Here we investigated the biological behaviors of NEK2 and the possible mechanisms of regulative effects of NEK2 on KDM5B in GC cell lines both in vitro and in vivo. The results showed that NEK2 and KDM5B were highly expressed in most of the 10 GC cell lines. NEK2 knockdown in MGC-803 cells led to suppression of cell proliferation and migration in vitro and tumor growth in vivo, while NEK2 overexpression in BGC-823 cells exhibited the reverse biological effect. When NEK2 was inhibited by NEK2 inhibitors or shNEK2, cellular KDM5B level decreased and H3K4me3 level increased, while overexpression of NEK2 resulted in enhanced KDM5B expression and decreased H3K4me3 level. Though direct interaction between NEK2 and KDM5B was excluded, NEK2 could regulate KDM5B/H3K4me3 expression through β-catenin/Myc both in vitro and in vivo, which was double confirmed by c-myc and KDM5B inhibitor experiments. Taken together, our study showed that NEK2 was highly expressed in GC cell lines and related to promoting cell proliferation, migration and tumor growth. A NEK2/β-catenin/Myc/KDM5B/H3K4me3 signaling pathway may contribute to the important carcinogenic role of NEK2-mediated malignant behaviors in GC.

Plasmonic photocatalysis has attracted significant attention but not been applied to acid-catalysed reactions. Here we report that visible-light irradiation of silver nanoparticles (AgNPs) significantly promotes Lewis acid-catalysis by several immobilised metal ions to dehydrate sugars, producing 5-hydroxymethylfurfural (HMF) in good yields at moderate temperatures. In one example, we achieved a 68 % yield of HMF for the conversion of d -glucose using immobilised Cr3+ ions and AgNPs under visible-light irradiation. The turnover number achieved in the presence of AgNPs is 13.4 times higher than in the absence of AgNPs. We propose a mechanism whereby sugar molecules coordinate to the metal ions, and light absorption by these metal complexes causes electron density distribution shift to the ions, thereby boosting the catalytic activity. Surface plasmon resonance by the AgNPs amplifies incident light to high intensities, considerably promoting catalytic activity. This plasmon-enhanced acid catalysis performance defines a new paradigm and expands photocatalysis applications.

In this work, bismuth bromideoxide (BiOBr), a typical visible-light photocatalyst, was coated with Zr-based MOFs (UiO-66) to prepare the BiOBr@UiO-66 photocatalysts with different mole ratios by the solvothermal method. The core–shell BiOBr@UiO-66 photocatalysts with abundant activated sites was obtained due to the modification of UiO-66 on the surface of BiOBr. The structure and properties of the BiOBr@UiO-66 photocatalysts were characterized by several methods. The 30% BiOBr@UiO-66 photocatalysts exhibited the biggest photodegradation rate constant (k = 0.0669 min−1) for RhB under visible-light irradiation than pure BiOBr (k = 0.0281 min−1) and UiO-66 (k = 0.0041 min−1). Additionally, the 30% BiOBr@UiO-66 photocatalysts exhibited the enhanced photocatalytic activity and stable recyclability due to the effective electron-hole separation and synergistic effect. The photocatalytic mechanism of the BiOBr@UiO-66 photocatalysts for RhB, which contained a photosensitization process, was discussed with the trapping experiment of active species and the proposed energy band alignments.

BF211, a bufalin (BF) derivative, exhibits stronger anti-cancer activity than BF but with potential cardiotoxicity. Fibroblast activation protein-α (FAPα) is a membrane-bound protease specifically expressed by carcinoma-associated fibroblasts, thus has been used for the selective delivery of anticancer agents. In this study, we used a FAPα-based prodrug strategy to synthesize a dipeptide (Z-Gly-Pro)-conjugated BF211 prodrug named BF211-03. BF211-03 was hydrolyzed by recombinant human FAPα (rhFAPα) and cleaved by homogenates of human colon cancer HCT-116 or human gastric cancer MGC-803 xenografts. In contrast, BF211-03 showed good stability in plasma and in the homogenates of FAPα-negative normal tissues, such as heart and kidney. In HCT-116 and MGC-803 cells with low levels of FAPα expression, BF211-03 displayed a lower in vitro cytotoxicity than BF211 with approximately 30 to 40-fold larger IC(50) values, whereas in human breast cancer MDA-MB-435 cells with high levels of FAPα expression, the IC(50) value difference between BF211-03 and BF211 was small (approximately 4-fold). Although the cytotoxicity of BF211-03 against tumor cells was dramatically decreased by the chemical decoration, it was restored after cleavage of BF211-03 by rhFAPα or tumor homogenate. In HCT-116 tumor-bearing nude mice, doubling the dose of BF211-03, compared with BF211, caused less weight loss, but showing similar inhibitive effects on tumor growth. Our results suggest that BF211-03 is converted to active BF211 in tumor tissues and exhibits anti-tumor activities in tumor-bearing nude mice. FAPα-targeted BF211-03 displays tumor selectivity and may be useful as a targeting agent to improve the safety profile of cytotoxic natural products for use in cancer therapy.