Novel biaryloxazolidinone derivatives with broad-spectrum antibacterial activity, favorable drug-like profiles and in vivo efficacy against linezolid-resistant Staphylococcusaureus.

The emergence of multidrug-resistant bacteria along with a declining pipeline of clinically useful antibiotics has led to the urgent need for the development of more effective antibacterial agents to treat drug-resistant bacteria. We previously discovered compound OB-158 with potent antibacterial activity but exhibited poor oral bioavailability. Herein, a systematic structural optimization of OB-158 to improve pharmacokinetic profiles yielded 26 novel biaryloxazolidinone analogues, and their activities against Gram-positive S. aureus, multidrug resistant S. aureus and Enterococcus faecalis were evaluated. Remarkably, compound 8b was identified with potent antibacterial activity against S. aureus (MIC = 0.06 µg/mL), MSSA (MIC = 0.125 µg/mL), MRSA (MIC = 0.06 µg/mL), LRSA (MIC = 0.125 µg/mL) and LREFa (MIC = 0.5 µg/mL). Compound 8b was demonstrated as a promising candidate through druglikeness evaluation including metabolism in microsomes and plasma, Caco-2 cell permeability, plasma protein binding, cytotoxicity, and inhibition of CYP450 and human monoamine oxidase. Notably, compound 8b displayed excellent PK profile with appropriate T1/2 of 1.49 h, high peak plasma concentration (Cmax = 2320 ng/mL), high plasma exposure (AUC0-t = 8310 h ng/mL), and superior oral bioavailability (F = 68.1 %) in Sprague-Dawley rats. Ultimately, in vivo efficacy of compound 8b in a mouse model of LRSA systemic infection was also demonstrated. Taken together, compound 8b represents a promising drug candidate for the treatment of linezolid-resistant Gram-positive bacterial strains infection.

Interface Engineering of MOF-Derived Co3O4@CNT and CoS2@CNT Anodes with Long Cycle Life and High-Rate Properties in Lithium/Sodium-Ion Batteries.

Metal-organic framework materials can be converted into carbon-based nanoporous materials by pyrolysis, which have a wide range of applications in energy storage. Here, we design special interface engineering to combine the carbon skeleton and nitrogen-doped carbon nanotubes (CNTs) with the transition metal compounds (TMCs) well, which mitigates the bulk effect of the TMCs and improves the conductivity of the electrodes. Zeolitic imidazolate framework-67 is used as a precursor to form a carbon skeleton and a large number of nitrogen-doped CNTs by pyrolysis followed by the in situ formation of Co3O4 and CoS2, and finally, Co3O4@CNTs and CoS2@CNTs are synthesized. The obtained anode electrodes exhibit a long cycle life and high-rate properties. In lithium-ion batteries (LIBs), Co3O4@CNTs have a high capacity of 581 mAh g-1 at a high current of 5 A g-1, and their reversible capacity is still 1037.6 mAh g-1 after 200 cycles at 1 A g-1. In sodium-ion batteries (SIBs), CoS2@CNTs have a capacity of 859.9 mAh g-1 at 0.1 A g-1 and can be retained at 801.2 mAh g-1 after 50 cycles. The unique interface engineering and excellent electrochemical properties make them ideal anode materials for high-rate, long-life LIBs and SIBs.

Discovery and optimization of dihydropteridone derivatives as novel PLK1 and BRD4 dual inhibitor for the treatment of cancer.

In this study, we have designed, synthesized and tested three series of novel dihydropteridone derivatives possessing isoindolin-1-one or isoindoline moieties as potent inhibitors of PLK1/BRD4. Remarkably, most of the compounds showed preferable inhibitory activity against PLK1 and BRD4. Compound SC10 exhibited excellent inhibitory activity with IC50 values of 0.3 nM and 60.8 nM against PLK1 and BRD4, respectively. Meanwhile, it demonstrated significant anti-proliferative activities against three tumor-derived cell lines (MDA-MB-231 IC50 = 17.3 nM, MDA-MB-361 IC50 = 8.4 nM, and MV4-11 IC50 = 5.4 nM). Moreover, SC10 exhibited moderate rat liver microsomal stability (CLint = 21.3 µL·min-1·mg-1), acceptable pharmacokinetic profile (AUC0-t = 657 ng·h·mL-1, oral bioavailability of 21.4 %) in Sprague-Dawley rats, reduced hERG toxicity, acceptable PPB and CYP450 inhibition. Further research indicated that SC10 could induce MV4-11 cell arrest at the S phase and apoptosis in a dose-dependent manner. This investigation provided us with an initial point for developing novel anticancer agents as dual inhibitors of PLK1 and BRD4.

Contributing to the Revolution of Electrolyte Systems via In Situ Polymerization at Different Scales: A Review.

Solid-state batteries have become the most anticipated option for compatibility with high-energy density and safety. In situ polymerization, a novel strategy for the construction of solid-state systems, has extended its application from solid polymer electrolyte systems to other solid-state systems. This review summarizes the application of in situ polymerization strategies in solid-state batteries, which covers the construction of polymer, the formation of the electrolyte system, and the design of the full cell. For the polymer skeleton, multiple components and structures are being chosen. In the construction of solid polymer electrolyte systems, the choice of initiator for in situ polymerization is the focus of this review. New initiators, represented by lithium salts and additives, are the preferred choice because of their ability to play more diverse roles, while the coordination with other components can also improve the electrical properties of the system and introduce functionalities. In the construction of entire solid-state battery systems, the application of in situ polymerization to structure construction, interface construction, and the use of separators with multiplex functions has brought more possibilities for the development of various solid-state systems and even the perpetuation of liquid electrolytes.

Design, synthesis, and biological evaluation of novel donepezil-tacrine hybrids as multi-functional agents with low neurotoxicity against Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and deficits in cognitive domains. Low choline levels, oxidative stress, and neuroinflammation are the primary mechanisms implicated in AD progression. Simultaneous inhibition of acetylcholinesterase (AChE) and reactive oxygen species (ROS) production by a single molecule may provide a new breath of hope for AD treatment. Here, we describe donepezil-tacrine hybrids as inhibitors of AChE and ROS. Four series of derivatives with a ß-amino alcohol linker were designed and synthesized. In this study, the target compounds were evaluated for their ability to inhibit AChE and butyrylcholinesterase (BuChE) in vitro, using tacrine (hAChE, IC50 = 305.78 nM; hBuChE, IC50 = 56.72 nM) and donepezil (hAChE, IC50 = 89.32 nM; hBuChE, IC50 = 9137.16 nM) as positive controls. Compound B19 exhibited an excellent and balanced inhibitory potency against AChE (IC50 = 30.68 nM) and BuChE (IC50 = 124.57 nM). The cytotoxicity assays demonstrated that the PC12 cell viability rates of compound B19 (84.37 %) were close to that of tacrine (87.73 %) and donepezil (79.71 %). Potential therapeutic effects in AD were evaluated using the neuroprotective effect of compounds against H2O2-induced toxicity, and compound B19 (68.77 %) exhibited substantially neuroprotective activity at the concentration of 25 µM, compared with the model group (30.34 %). Furthermore, compound B19 protected PC12 cells from H2O2-induced apoptosis and ROS production. These properties of compound B19 suggested that it was a multi-functional agent with AChE inhibition, anti-oxidative, anti-inflammatory activities, and low toxicity and that it deserves further investigation as a promising agent for AD treatment.

Overview of CFTR activators and their recent studies for dry eye disease: a review.

The cystic fibrosis transmembrane conductance regulator (CFTR) gets activated via the cAMP signaling pathway and is present in various secretory epithelial cells, including conjunctival and corneal epithelial cells. Activation of CFTR leads to fluid secretion in both mouse and human ocular surfaces. Dry eye disease is a significant health problem for which limited therapeutic options are available. In this review, on the one hand, small molecule CFTR activators with different chemical structures are summarized, and on the other hand, the pharmacological activity test and structural optimization of small molecule CFTR activators in the treatment of dry eye are outlined. The purpose of this review is to highlight the important role of CFTR activators in the treatment of dry eye disease and their potential as a new strategy for the treatment of dry eye disease.

Design and Synthesis of 1,3,5-Triazines or Pyrimidines Containing Dithiocarbamate Moiety as PI3Kα Selective Inhibitors.

Recent studies have shown that phosphoinositide 3-kinase (PI3K) plays a vital role in cell division, and it has become a therapeutic target for many cancers. In this paper, some new 1,3,5-triazine or pyrimidine skeleton derivatives containing dithiocarbamate were designed and synthesized based on the reasonable drug design strategy from the previously effective compound 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK-474), in order to get effective selective PI3Kα inhibitors that have not been reported in the literature. In addition, the inhibitory activities of these compounds on PI3Kα and two tumor cell lines in vitro (HCT-116, U87-MG) were evaluated. The representative compound 13 showed a half-maximal inhibitory concentration (IC50) value of 1.2 nM for PI3Kα and an exciting kinase selectivity. Compound 13 displayed strong efficacy in HCT-116 and U87-MG cell lines with IC50 values of 0.83 and 1.25 µM, respectively. In addition, compound 13 induced obvious tumor regression in the U87-MG cell line xenografts mouse model, with no obvious signs of toxicity after intraperitoneal injection at a dose of 40 mg/kg. Compound 13 can be an effective selective inhibitor of PI3Kα, and it provides patients with an opportunity to avoid the side effects related to the wider inhibition of the class I PI3K family.

Structure-based drug design, synthesis, and biological evaluation of novel 1,3,5-triazine or pyrimidine derivatives containing benzoyl hydrazine moiety as PI3Kα selective inhibitors.

Phosphoinositide 3-kinase (PI3K) was an important cellular signal transducer, while PI3Kα was the most mutated family member in cancer. Selective PI3Kα inhibitors have become the frequent research in recent years because of their excellent curative effect and reduced side effects. Here, we described a series of PI3Kα inhibitors with 1,3,5-triazine or pyrimidine skeleton containing benzoyl hydrazine based on the pan-PI3K inhibitor ZSTK474 relying on the strategies of structure-based drug discovery (SBDD) and computer-aided drug design (CADD). Among them, compound F8 exhibited improved selective PI3Kα inhibition with an IC50 value of 0.14 nM and more significant anti-proliferative activities against three tumor-derived cell lines (PC-3 IC50 = 0.28 µM, HCT-116 IC50 = 0.57 µM, and U87-MG IC50 = 1.37 µM) than ZSTK-474. Compound F-8 induced a great decrease in mitochondrial membrane which caused cell cycle arrest at G1 phase and apoptosis in U87-MG cells in a dose-dependent manner. Furthermore, compound F8 induced significant tumor regressions in a xenograft mouse model of U87-MG cell line with no clear evidence of toxicity following intraperitoneal injection of 40 mg/kg. Compound F8 may serve as a PI3Kα-selective inhibitor and provided the opportunity to spare patients the side effects associated with broader inhibition of the class I PI3K family.

Medicinal chemistry strategies targeting NLRP3 inflammasome pathway: A recent update from 2019 to mid-2023.

Nod-like receptor protein 3 (NLRP3), a therapeutic target that has a close relationship with inflammatory diseases, has drawn significant attention from researchers in the field. An increasing number of NLRP3 inhibitors have been reported since NLRP3 was identified as a biomarker and inflammatory therapeutic target. Inhibiting NLRP3 has been widely studied as therapeutics for the treatment of cryopyrin associated periodic syndrome (CAPS), inflammatory bowel disease (IBD), nonalcoholic steatohepatitis (NASH), arthrolithiasis, Alzheimer's disease (AD) and Parkinson's disease (PD). This review updates the recently reported (2019 to mid-2023) molecule inhibitors targeting the NLRP3 inflammasome pathway, summarizes their structure-activity relationships (SARs), and discusses the therapeutic effects on inflammatory diseases. I hope this review will contribute to the development of novel inhibitors targeting NLRP3 inflammasome pathway as potential drugs.

2-Aminopyrimidine derivatives as selective dual inhibitors of JAK2 and FLT3 for the treatment of acute myeloid leukemia.

Dual inhibitors of JAK2 and FLT3 can synergistically control the development of acute myeloid leukemia (AML), and overcome secondary drug resistance of AML that is associated with FLT3 inhibition. We therefore designed and synthesized a series of 4-piperazinyl-2-aminopyrimidines as dual inhibitors of JAK2 and FLT3, and improved their selectivity for JAK2. Screening cascades revealed that compound 11r exhibited inhibitory activity with IC50 values of 2.01, 0.51, and 104.40 nM against JAK2, FLT3, and JAK3, respectively. Compound 11r achieved a high selectivity for JAK2 at a ratio of 51.94, and also showed potent antiproliferative activity in HEL (IC50 = 1.10 µM) and MV4-11 (IC50 = 9.43 nM) cell lines. In an in vitro metabolism assay, 11r exhibited moderate stability in human liver microsomes (HLMs), with a half-life time of 44.4 min, and in rat liver microsomes (RLMs), with a half-life of 143 min. In pharmacokinetic studies, compound 11r showed moderate absorption (Tmax = 5.33 h), with a peak concentration of 38.7 ng/mL and an AUC of 522 ng h/mL in rats, and an oral bioavailability of 25.2%. In addition, 11r induced MV4-11 cell apoptosis in a dose-dependent manner. These results indicate that 11r is a promising selective JAK2/FLT3 dual inhibitor.

Design, synthesis, and biological evaluation of novel dihydropteridone derivatives possessing oxadiazoles moiety as potent inhibitors of PLK1.

Polo like kinase 1 (PLK1) is a serine/threonine kinase that is widely distributed in eukaryotic cells and plays an important role in multiple phases of the cell cycle. Its importance in tumorigenesis has been increasingly recognized in recent years. Herein, we describe the optimization of a series of novel dihydropteridone derivatives (13a-13v and 21g-21l) possessing oxadiazoles moiety as potent inhibitors of PLK1. Compound 21g exhibited improved PLK1 inhibitory capability with an IC50 value of 0.45 nM and significant anti-proliferative activities against four tumor-derived cell lines (MCF-7 IC50 = 8.64 nM, HCT-116 IC50 = 26.0 nM, MDA-MB-231 IC50 = 14.8 nM and MV4-11 IC50 = 47.4 nM) with better pharmacokinetic characteristics than BI2536 in mice (AUC0-t = 11 227 ng h mL-1vs 556 ng h mL-1). Moreover, 21g exhibited moderate liver microsomal stability and excellent pharmacokinetic profile (AUC0-t = 11227 ng h mL-1, oral bioavailability of 77.4%) in Balb/c mice, acceptable PPB, improved PLK1 inhibitory selectivity, and no apparent toxicity was observed in the acute toxicity assay (20 mg/kg). Further investigation showed that 21 g could arrest HCT-116 cells in G2 phase and induce apoptosis in a dose-dependent manner. These results indicate that 21g is a promising PLK1 inhibitor.

Stereoselective Synthesis of Substituted (Z)-N-Allyl Sulfonamides via a Palladium-Catalyzed Three-Component Tandem Reaction.

This paper reports the efficient synthesis of substituted (Z)-N-allyl sulfonamides via a palladium-catalyzed three-component tandem reaction of N-buta-2,3-dienyl sulfonamides with iodides and sulfonyl hydrazide or sulfinic acid sodium salt as nucleophiles. Pd(PPh3)4 (2.5 mol %), K2CO3, and THF were used as the optimal catalyst, base, and solvent, respectively. The substituted (Z)-N-allyl sulfonamides were obtained in a 30-83% overall yield. Mechanistic investigations revealed that the formation of the single (Z)-isomer was controlled by the formation of a six-membered palladacycle intermediate.

Design, synthesis, and evaluation of hydrazones as dual inhibitors of ryanodine receptors and acetylcholinesterases for Alzheimer's disease.

Alzheimer's disease (AD) implicates neuronal loss, plaque and neurofibrillary tangle formation, and disturbed neuronal Ca2+ homeostasis, which leads to severe dementia, memory loss, as well as thinking and behavioral perturbations that could ultimately lead to death. Calcium dysregulation and low acetylcholine levels are two main mechanisms implicated in Alzheimer's disease progression. Simultaneous inhibition of calcium oscillations (store overload-induced Ca2+ release [SOICR]) and acetylcholinesterase (AChE) by a single molecule may bring a new breath of hope for AD treatment. Here, we described some dantrolene derivatives as dual inhibitors of the ryanodine receptor and AChE. Two series of acylhydrazone/sulfonylhydrazone derivatives with aromaticgroup were designed and synthesized. In this study, the target compounds were evaluated for their ability to inhibit SOICR and AChE in vitro, using dantrolene and donepezil as positive controls. Compound 22a exhibited excellent and balanced inhibitory potency against SOICR (inhibition (%) = 90.1, IC50 = 0.162 µM) and AChE (inhibition (%) = 93.5, IC50 = 0.372 µM). Docking simulations showed that several preferred compounds could bind to the active sites of both the proteins, further validating the rationality of the design strategy. Potential therapeutic effects in AD were evaluated using the Barnes maze and Morris water maze tests, which demonstrated that compound 22a significantly improved memory and cognitive behavior in AD model mice. Moreover, it was also found that compound 22a could enhance synaptic strength by measuring hippocampal long-term potentiation (LTP) in brain slices. These results suggested that the introduction of a sulfonyl-hydrazone scaffold and aromatic substitution to dantrolene derivatives provided a useful template for the development of potential chemical entities against AD.

Based on 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474), design, synthesis and biological evaluation of novel PI3Kα selective inhibitors.

Based on 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474), three series of novel 1,3,5-triazine or pyrimidine derivatives containing semicarbazones have been designed and synthesized to obtain new potent and selective PI3Kα inhibitors. Their inhibitory activities in vitro were evaluated against PI3Kα and three tumor-derived cell lines (U87-MG, MCF-7, and PC-3). We also tested promising compounds (A4, A6, A10, and B1) for other PI3K class I subtype (PI3Kß, PI3Kδ, and PI3Kγ) activity. The representative compound A10 exhibited an IC50 value of 0.32 nM against PI3Kα, and demonstrated extraordinary subtype selectivity. Furthermore, compound A10 obviously inhibited proliferation of MCF-7 cell lines, induced a great decrease in mitochondrial membrane potential leading to apoptosis of cancer cells, and arrested G2 phase in a dose-dependent manner. Additionally, compound A10 induced significant tumor regressions in a xenograft mouse model of U87-MG cell line without an obvious sign of toxicity upon 20 mg/kg oral administration. Compound A10 may serve as a PI3Kα-selective inhibitor and provide the opportunity to spare patients the side effects associated with broader inhibition of the class I PI3K family.

Discovery of novel 7,7-dimethyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidines as ATR inhibitors based on structure-based drug design.

ATR kinase is essential to the viability of replicating cells responding to the accumulation of single-strand breaks in DNA, which is an attractive anticancer drug target based on synthetic lethality. Herein we design, synthesize, and evaluate a novel series of fused pyrimidine derivatives as ATR inhibitors. As a result, compound 48f, with an IC50 value of 0.0030 µM against ATR, displayed strong monotherapy efficacy in ataxia-telangiectasia mutated (ATM) kinase-deficient tumor cells LoVo, SW620, OVCAR-3 cell lines with IC50 values of 0.040 µM, 0.095 µM, 0.098 µM, respectively. More importantly, the combination of 48f with AZD-1390, cisplatin, oxaliplatin, and olaparib respectively resulted in synergistic activity against HT-29, HCT116, A549, MCF-7, MDA-MB-231 cells. Moreover, 48f showed a favorable pharmacokinetic profile with a bioavailability of 30.0% in SD rats, acceptable PPB, high permeability (Papp A to B = 8.23 cm s-1 × 10-6), and low risk of drug-drug interactions. Collectively, compound 48f could be a promising compound for further investigation.

Discovery of benzamide derivatives containing urea moiety as soluble epoxide hydrolase inhibitors.

The elevation of epoxy-fatty acids through inhibition of soluble epoxide hydrolase (sEH) is efficient for the treatment of inflammatory and pain-related diseases. Herein, we reported the discovery of a series of benzamide derivatives containing urea moiety as sEH inhibitors. Intensive structural modifications led to the identification of compound A34 as a potent sEH inhibitor with good physicochemical properties. Molecular docking revealed an additional hydrogen-bonding interaction between the unique amide scaffold and Phe497, contributing to sEH inhibition potency enhancement. Compound A34 exhibited outstanding inhibitory activity against human sEH, with an IC50 value of 0.04 ± 0.01 nM and a Ki value of 0.2 ± 0.1 nM. It also showed moderate systemic drug exposure and oral bioavailability in vivo metabolism studies. In carrageenan-induced inflammatory pain rat model, compound A34 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib. Metabolism studies in vivo together with an inflammatory pain evaluation suggest that A34 may be a viable lead compound for the development of highly potent sEH inhibitors.

Synthesis and biological evaluation of new series of benzamide derivatives containing urea moiety as sEH inhibitors.

The pharmacological inhibition of soluble epoxide hydrolase (sEH) was shown to reduce inflammation and pain. Herein, we described a series of newly synthesized sEH inhibitors with the trident-shaped skeleton. Intensive structural modifications led to the identification of compound B15 as a potent sEH inhibitor with an IC50 value of 0.03 ± 0.01 nM. Furthermore, compound B15 showed satisfactory metabolic stability in human liver microsomes with a half-time of 197 min. In carrageenan-induced inflammatory pain rat model, compound B15 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib, which demonstrated the proof of potential as anti-inflammatory agents for pain relief.

Discovery of 4-phenylindolines containing a (5-cyanopyridin-3-yl)methoxy moiety as potent inhibitors of the PD-1/PD-L1 interaction.

With the great success of anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) monoclonal antibodies in clinical applications, blocking the PD-1/PD-L1 pathway has become the most compelling strategy in the field of tumor immunotherapy. In this study, a novel series of 4-phenylindolines containing a (5-cyanopyridin-3-yl)methoxy moiety were developed, and their structure-activity relationships were preliminarily discussed. Among them, compounds M17 and M23 exhibited the most potent ability to disrupt the PD-1/PD-L1 interaction, demonstrating IC50 values of 60.1 nM and 53.2 nM, respectively. The binding mode of M23 was further explored by molecular docking analysis with dimeric PD-L1. Therefore, M17 and M23 are promising lead compounds for developing potent inhibitors of the PD-1/PD-L1 axis.

Novel 4-phenoxypyridine derivatives bearing imidazole-4-carboxamide and 1,2,4-triazole-3-carboxamide moieties: Design, synthesis and biological evaluation as potent antitumor agents.

Two series of novel 4-phenoxypyridine derivatives containing imidazole-4-carboxamide and 4-methyl-5-oxo-4,5-dihydro-1,2,4-triazole-3-carboxamide moieties were synthesized and evaluated for their in vitro inhibitory activities against c-Met kinase and antiproliferative activities against MKN-45, A549 and H460 cancer cell lines. The results indicated that most of the compounds showed moderate to good antitumor activities. The most promising compound T14 (with c-Met IC50 value of 0.012 µM) showed remarkable antiproliferative activities against MKN-45, A549 and H460 cell lines with IC50 values of 0.64 µM, 1.92 µM and 2.68 µM, respectively. Their preliminary structure-activity relationships (SARs) studies indicate that imidazole-4-carboxamide was more preferred as linker part, and electron-withdrawing groups (especially halogen groups) on the terminal phenyl rings were beneficial for improving the antitumor activities.

Discovery of 4-Arylindolines Containing a Thiazole Moiety as Potential Antitumor Agents Inhibiting the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Interaction.

Through specific structural modification of a 4-phenylindoline precursor, new 4-arylindolines containing a thiazole moiety were developed and found to be promising modulators of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis. Compound A30 exhibited outstanding biochemical activity, with an IC50 of 11.2 nM in a homogeneous time-resolved fluorescence assay. In the cell-based assay, A30 significantly promoted IFN-γ secretion and rescued T-cell proliferation, which were inhibited by PD-1 activation. Furthermore, A30 showed favorable in vivo antitumor activity in a mouse 4T1 breast carcinoma model. Moreover, in mouse CT26 colon carcinoma models, A30 potently suppressed the growth of CT26/PD-L1 tumor but did not obviously affect the growth of CT26/vector tumor. The results of flow cytometry analysis indicated that A30 inhibited tumor growth by activating the immune microenvironment. We concluded that A30 is a new starting point for further development of PD-1/PD-L1 interaction inhibitors as antitumor agents.