Microbiology/Virology

<p>Cap-dependent endonuclease-IN-25 is a potent inhibitor of CEN, useful in studying Orthomyxoviridae viruses. (See WO2020075080A1, compound 4.)</p>

<p>Secutrelvir inhibits the 3CL protease (3CL protease), thereby exhibiting antiviral activity by preventing the replication of SARS-CoV-2.</p>

<p>Eravacycline (TP-434) is a potent and broad-spectrum antibacterial agent.</p>

<p>Faldaprevir is an orally effective, selective, non-covalent HCV NS3/4A protease inhibitor with high inhibitory activity against HCV 1a and 1b genotype.</p>

<p>Anti-MRSA agent 6 (compound 3q6) is a potent anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) agent with low cytoxicity for MCF-7, A549 cells [1].</p>

<p>2'-Amino-2'-deoxyadenosine (9-(2-Amino-2-deoxypentofuranosyl)-9H-purin-6-amine) is a nucleoside antibiotic that effectively inhibits various Mycoplasma strains.</p>

<p>PqsR-IN-1, potent PqsR inhibitor, curbs pyocyanin in Pseudomonas aeruginosa with low cytotoxicity.</p>

<p>Trans-Clopenthixol ((E)-Clopenthixol) is an antibiotic without any sedative properties. It can be used in vitro to inhibit Pseudomonas aeruginosa and Plasmodium falciparum.</p>

<p>Saphenamycin is an antibiotic from a strain of Streptomyces.</p>

<p>NBD-14189: Potent HIV-1 entry blocker, binds gp120, IC50: 89 nM, strong antiviral (EC50 &lt;200 nM).</p>

<p>RSV-IN-5: Dual inhibitor for RSV fusion proteins, effective on wild-type A2 and D486N mutant with EC50s of 2.0 nM &amp; 8.1 nM. Potent anti-RSV.</p>

<p>LolCDE-IN-2 is a potent Lol protein (LolCDE) inhibitor. LolCDE-IN-2 shows antibacterial activity with a MIC of 2 μg/ml against E. coli MG1655 [1].</p>

<p>Neuraminidase-IN-11 (15e) inhibits H1N1 (IC50: 4.7nM), H5N1 (8.46nM), H5N8 viruses (1.5nM) selectively &amp; potently.</p>

<p>RdRP-IN-5 (compound 20), a potent inhibitor of the influenza virus RNA-dependent RNA polymerase (RdRP), has potential application in influenza research [1].</p>

<p>(E)-Cefodizime ((E)-THR-221) is an antibiotic that selectively binds to penicillin-binding proteins (PBPs), inhibiting bacterial cell wall synthesis, which results in its antibacterial activity. It holds potential for research into various bacterial infections, including the prevention of preoperative infections.</p>

<p>Anti-MRSA agent 27 (compound 4a) is a potent antimicrobial agent against methicillin-resistant Staphylococcus aureus (MRSA) with a minimum inhibitory concentration (MIC) of 0.0975 μmol/L. It effectively disrupts MRSA biofilms and inhibits the production of hemolysins.</p>

<p>A25822B is an antifungal agent.</p>

<p>β-Glucuronidase-IN-2 is a potent inhibitor of E.</p>

<p>Anti-infective agent 10 (Compound Example 30) is an ns5b polymerase inhibitor that functions as an anti-HCV agent.</p>

<p>Compound 6q, a trifluoromethylpyridine oxadiazole, targets Xanthomonas oryzae with EC50 of 7.2 μg/mL.</p>

<p>(Rac)-Plevitrexed is a racemate of Plevitrexed. Plevitrexed is an orally active and potent inhibitor of thymidylate synthase (TS).</p>

<p>GTSE1-IN-1 (compound Y18), an orally active GTSE1 inhibitor, exhibits notable anticancer properties. It effectively represses the proliferation of cancer cells by downregulating GTSE1 transcription and expression, which leads to DNA damage and promotes persistent cell cycle arrest and cellular senescence. Moreover, GTSE1-IN-1 substantially reduces the adhesion, migration, and invasion of colorectal cancer HCT116 cells and non-small cell lung cancer A549 cells in vitro.</p>

<p>Anti-MRSA agent 2 inhibits MRSA at 0.098 μg/ml, with low toxicity and disrupts bacterial membranes and DNA.</p>

<p>17,17-Ethylendioxyandrost-5-en-3β-ol, with an EC 50 of 629 μM, acts as an inhibitor of HSV-1. This compound is applicable in research studies focusing on viral infections.</p>

<p>Ambelline has antitumor activity.</p>

<p>Compound 25b inhibits DENV2/ZIKV NS2B/NS3 proteases; IC50: ZIKV 0.67μM, DENV2 4.38μM.</p>

<p>HBV-IN-24 inhibits HBV DNA, HBsAg, HBeAg (EC50: 0.6, 0.6, 4.6 nM), and has antiviral properties with neurotoxicity mitigation.</p>

<p>GSK 932121: potent antimalarial, targets P. falciparum by inhibiting cytochrome bc1 in the electron transport chain.</p>

<p>FtsZ-IN-13 (Compound C11) functions as an inhibitor of the temperature-sensitive mutant Z (FtsZ), exhibiting IC50 values of 47.97 μM for FtsZSa and 34 μM for FtsZPa. It demonstrates notable antibacterial activity against Staphylococcus aureus (with a minimum inhibitory concentration of 2 μg/mL), cystic fibrosis Staphylococcus aureus clinical isolates, and methicillin-resistant Staphylococcus aureus (MRSA). FtsZ-IN-13 is applicable in research on antibiotic resistance.</p>

<p>Narlaprevir (SCH 900518) is an HCV NS3 inhibitor with anti-HCV activity, inhibiting SARS-CoV-2, and useful in virus infection research.</p>

<p>E6-272, an inhibitor of HPV 16, induced early and late apoptosis in HPV16-positive cervical cancer cells and inhibited the proliferation of SiHa and CaSki.</p>

<p>HBV-IN-48, an HBV inhibitor, exhibits potent antiviral activity against HBV in HepDE19 cells, demonstrated by its EC 50 value of 0.005 μM. Additionally, it effectively reduces serum HBV DNA levels in mouse models of HBV infection.</p>

<p>Werner syndrome RecQ helicase-IN-2 is a potent Werner syndrome RecQ DNA helicase (WRN) inhibitor, useful in research on colorectal and gastric cancers.</p>

<p>Emtricitabine triphosphate is an active metabolite of Emtricitabine, a drug for HIV/HBV that inhibits reverse transcriptase.</p>

<p>MsbA-IN-2 is a potent inhibitor of the lipopolysaccharide transporter MsbA and is able to act on E. coli MsbA (IC50: 2 nM).</p>

<p>GSK_WRN4 is a WRN helicase inhibitor with anti-cancer activity, inhibiting MSI tumor cell growth by inducing DNA double-strand breaks, useful in cancer research</p>

<p>DNA ligase-IN-2 (compound 2) acts as a potent LigA inhibitor, effectively hindering the DNA-independent spontaneous adenylation activity of full-length LigA and the truncated enzyme LigA:AD with an IC50 of 29 nM. It also significantly suppresses the in vitro growth of Staphylococcus aureus, showing MIC values of 1 μg/mL for S. aureus ATCC 29213 and S. aureus ATCC 700699, while the MIC for Escherichia coli (E. coli) ATCC 25922 is &gt;64 μg/mL.</p>

<p>Lamivudine, a drug for HIV-1 and HBV, inhibits reverse transcriptase and resembles zalcitabine.</p>

<p>NDM-1 inhibitor-3 is a New Delhi Metallo-β-lactamase-1 (NDM-1) inhibitor (Ki : 4 μM) widely found in nature and is associated with antibiotic resistance.</p>

<p>HIV-1 inhibitor-41 (B23): Oral non-nucleoside reverse transcriptase blocker, EC50 of 50 nM (E138K), 20.8 nM (WT), low hERG/CYP impact, non-toxic.</p>

<p>NFC nitro probe 1 (compound 18) is a chemical probe designed for the detection of Mtb, exhibiting high potency against both R-Mtb and NR-Mtb.</p>

<p>PLpro-IN-6 (compound 6) serves as an inhibitor for the papain-like protease (PLpro), demonstrating potent activity with an IC 50 of 0.019 μM against the SARS-CoV-2 PLpro enzyme.</p>

<p>GC373, an effective inhibitor of the SARS-CoV-2 M pro, impedes virus replication, exhibiting an inhibition concentration (IC 50) of 0.4 μM. This compound is valuable for use in anti-COVID-19 research.</p>

<p>LN002 is an orally active inhibitor of Cryptosporidium oxidase, utilized for research in cryptosporidiosis.</p>

<p>Valopicitabine, a NS5B inhibitor, is used potentially for the treatment of HCV infection.</p>

<p>ABT-072 is a nonnucleoside NS5B polymerase inhibitor and a candidate drug evaluated for treatment of hepatitis C virus.</p>

<p>UNI418 is a dual inhibitor targeting PIKfyve and PIP5K1C, exhibiting antiviral activity against SARS-CoV-2 (EC50=1.4 μM). It inhibits the endocytosis of the virus mediated by ACE2 by suppressing PIP5K1C (IC50=60.1 nM; Kd=61 nM). Additionally, UNI418 impedes the entry of SARS-CoV-2 into host cells by inhibiting the proteolytic activation regulated by PIKfyve (Kd=0.78 nM).</p>

<p>PLpro-IN-5 (compound 21), serving as a PLPro protease inhibitor, boasts an IC50 of 91.14 nM. This compound exhibits a broad-spectrum antivirus efficacy, particularly effective against SARS-CoV, MERS-CoV, and SARS-CoV-2.</p>

<p>Antibacterial agent 76 (compound 9) is a potent antibacterial agent.</p>

<p>Antileishmanial agent-6: potent against Leishmania donovani, IC50 0.54μM; cytotoxic IC50 10.2μM.</p>

<p>Neocryptolepine-Cl (compound Z24) is an inhibitor of Bcthi4, demonstrating excellent antifungal activity against B. cinerea, with an EC50 value of 0.56 μg/mL.</p>

<p>ATIC-IN-2 (Compound 1) is a competitive inhibitor of the bifunctional enzyme AICAR Tfase/IMPCH (ATIC), binding to inosine monophosphate cyclohydrolase (IMPCH) with a Ki of 0.13 μM.</p>

<p>Anti-Trypanosoma cruzi agent-1 (Compd E5) has a potent anti-Toxoplasma effect.</p>

<p>Neuraminidase-IN-4 inhibits neuraminidase (EC50: 1.59 μM) and has strong anti-H5N1 activity.</p>

<p>SARS-CoV-2-IN-99 (compound 58) is an inhibitor of the main protease of SARS-CoV-2.</p>

<p>1,5-Dideoxy-1,5-imino-D-mannitol is an antibiotic with antibacterial properties.</p>

<p>Laninamivir trifluoroacetate, a long-acting antiviral, treats and prevents Influenza A and B via nasal spray.</p>

<p>Meclocycline: a tetracycline antibiotic, inhibits LDH, reduces cell toxicity from mutant huntingtin, doesn't change protein levels in PC12 cells.</p>

<p>HldA/E-IN-1 (compound 8) is a dual inhibitor of HldA/E, exhibiting IC50 values of 17.2 μM and 67.8 μM, respectively. This compound is utilized in research on antibacterial infections.</p>

<p>Compound 9b inhibits CHS with an IC50 of 0.21 mM; it's a broad-spectrum antifungal, effective against resistant strains.</p>

<p>Cefoxazole is a β-lactam antibiotic featuring an isoxazole structure, known for its antibacterial activity. It can be utilized in the study of infectious diseases.</p>

<p>Telinavir (SC-52151) is a potent and selective inhibitor of HIV protease. It effectively inhibits both HIV-1 and HIV-2, as well as lymphotropic, monocytotropic strains, and wild isolates of simian immunodeficiency viruses, with an EC50 of 26 ng/mL (43 nM). Telinavir shows high protein binding in human plasma and a low distribution rate in red blood cells.</p>

<p>Antibacterialagent 279 (compound A12) is an effective antibacterial agent. It inhibits the SOS response of Pseudomonas aeruginosa.</p>

<p>Tenellin is a fungal metabolite that inhibits Mg2+-, Ca2+-, and Na+/K+-ATPase activities in erythrocytes. Tenellin is cytotoxic to Sf9 and Sf21 insect cells.</p>

<p>Compound 11: Sulfonylurea derivative, antimicrobial, anticancer; MIC 0.039-0.156 mg/mL; A549 IC50: 19.7 μg/mL, PC3 IC50: 11.9 μg/mL.</p>

<p>Ceftolozane TFA is a cephalosporin class antibiotic (antibiotic) designed to inhibit Gram-negative bacterial infections. Additionally, it can be utilized in the synthesis of novel antibiotics (antibiotic) that are more efficacious and safer.</p>

<p>DRF-8417 is an oxazolidinone antibiotic, active against both Gram-positive bacteria and fastidious Gram-negative bacteria. The MIC50 and MIC90 values of DRF-8417 for Gram-positive pathogens range between 0.06-1 mg/L.</p>

<p>Plevitrexed, an oral TS inhibitor (Ki: 0.44 nM), targets α-folate receptor &amp; reduced folate carrier, treats gastric cancer.</p>

<p>Colistin adjuvant-1, inhibits NF-κB (IC50: 0.209 μM), boosts mucin against gram-negative bacteria.</p>

<p>Penethamate hydriodide is a diethylaminoethyl ester prodrug of penicillin, utilized via intramuscular injection to treat mastitis in cattle.</p>

<p>MT0703 is a cephalosporin antibiotic featuring an aminothiazolylglycyl moiety with a 1,5-dihydroxy-4-pyridinone-2-carbonyl group, displaying potent activity against Pseudomonas species.</p>

<p>TKB272 is an orally active antiviral agent that selectively targets the main protease (Mpro) of SARS-CoV-2, effectively inhibiting the infection and replication of various strains, including Omicron variants (such as XBB.1.5 and EG.5.1). It exhibits an enzyme inhibitory activity with an IC50 of 0.7 µM against SARS-CoV-2WK-521 Mpro and shows potent antiviral activity at the cellular level with an EC50 as low as 2.6 nM in HeLahACE2-TMPRSS2 cells against the BQ.1.1 strain. TKB272 also has a CC50 of 98 µM, indicating low cytotoxicity. Furthermore, it demonstrates a significant suppression of SARS-CoV-2XBB.1.5 replication in the B6.Cg-Tg(K18-hACE2)2-Prlmn/J transgenic mouse model, suggesting potential use in the research of SARS-CoV-2 infections.</p>

<p>WM382, a potent dual PMIX/X inhibitor, has IC50s of 1.4 nM/0.03 nM and effective against various malaria stages.</p>

<p>SARS-CoV-2-IN-100 (Compound 172) is a broad-spectrum antiviral agent against various SARS-CoV-2 variants. It works synergistically with Nirmatrelvir to reduce the risk of antiviral resistance.</p>

<p>CHS inhibitor 9: a broad-spectrum antifungal for studying fungal infections.</p>

<p>Carbonic anhydrase inhibitor28 (Compound 11) serves as an inhibitor for the Pseudomonas aeruginosa carbonic anhydrase. It exhibits antibacterial activity, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 0.5 and 1 μg/mL, respectively, against P. aeruginosa. Carbonic anhydrase inhibitor28 is utilized in research focused on anti-infection applications.</p>

<p>WRN inhibitor 11 (Example 17) is an orally effective inhibitor of WRN helicase, with an IC50 of 63 nM.</p>

<p>Antifungalagent 125 (compound 4H) is a potent succinate dehydrogenase (SDH) inhibitor with an IC50 of 3.59 μg/mL and exhibits fungicidal activity against Alternaria alternata.</p>

<p>CDA-IN-2 (Compound VS#2-3) is an inhibitor of chitin deacetylase (CDA) that exhibits antifungal properties. At a concentration of 100 μM, it inhibits P. xanthii's CDAPxCDA1 by 83.7% and PxCDA2 by 74.5%. CDA-IN-2 is applicable in research on agricultural fungal diseases, including resistance to powdery mildew and gray mold.</p>

<p>(R)-ZG197: Activates Sa ClpP (EC50=1.5μM) &amp; Hs ClpP (EC50=31.4μM); selective for Sa ClpP.</p>

<p>Glutamate-5-kinase-IN-2 (compound 54) is a potent G5K inhibitor with 4.2 μM MIC, potential in anti-TB research.</p>

<p>SARS-CoV-2 nsp14-IN-2: Strong Nsp14 methyltransferase inhibitor (IC50: 0.09 μM), potential for COVID-19 research.</p>

<p>Antibacterial agent 78 (compound 30) is an antibacterial agent with improved cytotoxicity profile[1].</p>

<p>SP-471 is a potent inhibitor of dengue virus (DENV) protease (IC50: 18 μM) and inhibits the inter- and intramolecular protease processes of DENV.</p>

<p>MsbA-IN-5 (compound 40) is a potent and highly selective inhibitor of MsbA (IC50: 2 nM). MsbA-IN-5 can be used in Gram-negative studies.</p>

<p>Mt KARI-IN-1 inhibits Mtb KARI with a 3.06 μM Ki, targeting tuberculosis.</p>

<p>AG-7404: strong protease inhibitor, fights poliovirus, EC50 0.080-0.674 μM, effective on V-073-resistant strains.</p>

<p>Antibiofilm agent-14 (compound 11) functions as an antibiofilm agent. It exhibits antifungal activity against C.albicans SC5314, with a minimum inhibitory concentration (MIC) of 50 μM.</p>

<p>C-467929 is an inhibitor of the Nsp15 endoribonuclease, exhibiting an IC50 value of 8 μM. This compound binds to the SARS-CoVNsp15 protein and is applicable for infection research.</p>

<p>SARS-CoV-2-IN-82 (compound A) acts as an inhibitor of the Programmed-1 ribosomal frameshift (-1 PRF) in SARS-CoV-2 [1].</p>

<p>BAR-072 is a small molecule inhibitor targeting TraE with a KD value of 2.7 µM. It significantly suppresses the transfer of the antibiotic resistance-associated plasmid pKM101. BAR-072 holds promise as a candidate molecule for research in disease areas related to infection and resistance control, by inhibiting the spread of bacterial resistance genes.</p>

<p>PqsR-IN-2, potent PqsR inhibitor, curbs Pseudomonas aeruginosa communication, reduces pyocyanin, with low toxicity.</p>

<p>Palmitanilide (Palmitic acid anilide) is an antimicrobial agent effective against Gram-positive bacteria. It can electrostatically bind to components of the cell wall of Gram-positive bacteria (such as Bacillus cereus), altering the membrane structure and affecting normal cellular functions. Palmitanilide shows potential for research into infections caused by Gram-positive bacteria.</p>

<p>PolQi1 is a highly efficient and selective Polϴ (DNA polymerase theta) inhibitor with an IC50 of 2 nM, showing potential for cancer therapy.</p>

<p>Antitubercular agent-11 (Compound 1e) is an antitubercular agent with a bulkier electron-donating group (Bu-t) that shows the best MIC value of 0.060 μg/mL [1].</p>

<p>epi-D-Captopril (epi-D-SQ 14225) is a stereoisomer of Captopril and functions as an inhibitor of metallo-beta-lactamases (MBLs). The IC50 values of epi-D-Captopril for NDM-1, IMP-1, and VIM-2 are 64 μM, 173 μM, and 5.5 μM, respectively. This compound holds potential for research in MBLs-related antibiotic-resistant infections.</p>

<p>Compound 15f, a Clofazimine derivative, inhibits rabies (EC50: 1.45 μM) and SARS-CoV-2 (EC50: 14.6 μM).</p>

<p>CYP2C19-IN-1: potent CYP2C19 inhibitor, non-genotoxic, non-hepatotoxic, blocks RdRP (Ki: 6.16 μM), useful for ZIKV research.</p>

<p>Antitubercular agent-15 (5n): low toxicity, fights M. tuberculosis strains; MIC90 values range 0.73-18.8 μg/mL.</p>

<p>Doxazosin impurity 12 acts as an inhibitor of CTX-M β-lactamase (Beta-lactamase) with a Ki value of 0.7 mM against CTX-M.</p>