Microbiology/Virology

<p>NHS-modified coumarin, 4,5'-Dimethylangelicin-NHS, shows photochemical activity &amp; photosensitivity.</p>

<p>Compound 11i: potent, non-toxic anti-tuberculosis biphenyl analogue.</p>

<p>NS2B/NS3-IN-3 (Compd 66) is an inhibitor of Flavivirus NS2B-NS3 protease [1] .</p>

<p>Cap-dependent endonuclease-IN-5 inhibits CEN and fights influenza with low toxicity and good in vivo properties.</p>

<p>Cis-RdRP-IN-5 is an effective inhibitor of the influenza virus RNA-dependent RNA polymerase (RdRP), employed in influenza virus research.</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>Deprodone is an active compound that inhibits key processes such as bacterial cell wall synthesis by interacting with hydrolase and transferase proteins of methicillin-resistant Staphylococcus aureus (MRSA). It is applied in the research of MRSA infections, inflammatory skin diseases, intestinal disorders, and fatty acid metabolism disorders.</p>

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

<p>SARS 3CLpro-IN-1: stereospecific SARS 3CL protease inhibitor, octahydroisochromene class, IC50 = 95 μM.</p>

<p>DNA crosslinker 6 (compound 1) is an anti-mitotic agent known for its strong binding affinity to AT-DNA and inhibition of AT-hook 1 binding to DNA (IC50=0.03 µM). Additionally, it exhibits anti-protozoal activity, effectively inhibiting T. brucei with an EC50 of 0.83 µM.</p>

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

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

<p>PFK-IN-1 (compound 1) is an inhibitor of 6-phosphofructo-1-kinase (PFK), demonstrating IC50 values of 0.41 and 0.23 μM against T. brucei and T. cruzi PFK, respectively, and an ED50 of 15.18 μg/mL for T. brucei. The compound has a half-life of 9.7 minutes in rat liver microsomes and 408 minutes in mouse liver microsomes.</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>Glutamate-5-kinase-IN-2 (compound 54) is a potent G5K inhibitor with 4.2 μM MIC, potential in anti-TB research.</p>

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

<p>XR8-89, a potent PLpro inhibitor (IC50=0.1μM), blocks SARS-CoV-2 replication; useful for research.</p>

<p>Compound 15c selectively inhibits SARS-CoV-2 nsp3 Mac1 with IC50 of 6.1 μM.</p>

<p>MRL-494, a small-molecule BamA inhibitor, resists efflux and outer membrane permeability, with antibacterial properties.</p>

<p>SARS-CoV-2-IN-23 (compound GRL-0617) is an inhibitor of SARS-COV-2 papain-like protease (PLpro) (IC 50 = 2.3 μM) [1].</p>

<p>Antimalarial 9, a quinoline-imidazole derivative, effectively targets CQ-susceptible (IC50-0.14 μM) and MDR strains (IC50-0.41 μM) with low toxicity.</p>

<p>ACHN-975: potent LpxC inhibitor with subnanomolar activity; targets many gram-negative bacteria; MIC ≤1 μg/mL.</p>

<p>(E)-2,6-Di-tert-butyl-4-(4-(diethylamino)styryl)pyrylium TFA (Compound 4a) functions as a Gram-negative outer membrane permeabilizer by targeting Met47 in LptA to disrupt LptA/LptC interactions, exhibiting synergistic antibacterial activity. This compound, when in the form of (trifluoromethanesulfonate), enhances the efficacy of pol B against both wild-type and multi-drug resistant A. baumannii and E. coli strains. Additionally, (E)-2,6-Di-tert-butyl-4-(4-(diethylamino)styryl)pyrylium (trifluoromethanesulfonate) serves as an adjuvant for antibiotics combating multi-drug resistant Gram-negative bacteria.</p>

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

<p>Antifungalagent 127 (Compound 6c) is an antifungal agent with potent inhibitory activity against Botrytis cinerea and Rhizoctonia solani.</p>

<p>WQ3810 TFA is an orally available fluoroquinolone with antimicrobial activity against Mycobacterium tuberculosis and inhibits the DNA rotamase activity of</p>

<p>Antifungal agent 17 showed good antifungal activity against B. cinerea (EC50: 2.86 μg/mL).</p>

<p>MraY-IN-3 (12a) is a potent inhibitor of the bacterial translocase MraY (IC50: 140 μM). 46 μg/ml).</p>

<p>SARS-CoV-2-IN-24 blocks PLpro, altering its shape and stopping virus replication—useful for SARS-CoV-2 research.</p>

<p>Anticaries agent-1 (Compound 21b) is utilized as an anticaries agent. It effectively inhibits biofilm formation with an IC50 of 77 μM and restricts the growth of S. mutans.</p>

<p>SARS-CoV-2-IN-22 is a SARS-CoV-2 pseudovirus inhibitor (IC50: 16.96 μM).</p>

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

<p>RAD51-IN-8 inhibits RAD51-BRCA2 interaction and H4A4 with EC50 of 19 μM; a micromolar PPI inhibitor.</p>

<p>DC-159a, an 8-methoxy fluoroquinolone, possesses broad-spectrum antibacterial activity, with a particular efficacy against Gram-positive pathogens. The MIC90 values for DC-159a are 0.5 μg/mL against Streptococcus anginosus group, 4 μg/mL against Clostridium difficile, and 2 μg/mL against Bacteroides fragilis.</p>

<p>Polθ-IN-8 (example 77) is a DNA polymerase θ (Polθ) inhibitor with an IC50 for Polθ ATPase activity of less than 100 nM. Polθ-IN-8 is useful for researching diseases related to Polθ activity, such as cancer.</p>

<p>FNC-TP trisodium, active intracellular FNC form, inhibits NRTI, fights HIV, HBV, and HCV.</p>

<p>GHP-88309 is an orally active, broad-spectrum anti-paramyxovirus agent that targets viral polymerase, interrupting viral RNA synthesis. It effectively inhibits respiratory syncytial virus (RSV), measles virus (MeV), and canine distemper virus (CDV) with an EC50 of 0.06-1.2 μM. In mouse models, GHP-88309 demonstrates significant anti-infective activity.</p>

<p>Compound (S,R)-48 inhibits Pf, Pv, &amp; Tbr PRT with Ki of 50, 20, 2 nM.</p>

<p>Fipravirimat is a potent inhibitor of HIV-1 with potential applications in HIV and AIDS research.</p>

<p>VV261 is an orally active inhibitor of the Influenza Virus. It exhibits activity against the Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) and the Lymphocytic Choriomeningitis Virus (LCMV), with EC50 values of 0.89 and 0.15, respectively.</p>

<p>Succinate dehydrogenase-IN-8 (compound i19) is a potent inhibitor of succinate dehydrogenase (SDH). This indanoyl amino acid derivative demonstrates strong antifungal activity in vitro against Rhizoctonia solani (EC50 = 0.1843 mg/L), Botrytis cinerea (EC50 = 0.4829 mg/L), and Sclerotinia sclerotiorum (EC50 = 0.1349 mg/L).</p>

<p>LN-439A (compound LN-439A) is a novel BAP1 inhibitor that suppresses the growth of basal-like breast cancer by degrading KLF5.</p>

<p>SARS-CoV-2 Mpro-IN-25 (Compound 3a) is a protease inhibitor for SARS-CoV-2, exhibiting an IC50 value of 0.26 μM. It demonstrates antiviral activity and is useful for research in the field of pneumonia.</p>

<p>CDK9-IN-34 (Compound 1b) is an inhibitor of CDK9 with an IC50 of 0.25 μM. It exhibits cytotoxicity against cancer cell lines HCT116, MCF7, and K652, with IC50 values of 1.43 μM, 3.01 μM, and 50.27 μM, respectively. Additionally, CDK9-IN-34 demonstrates antiviral activity against coronavirus 229E with an IC50 of 145.92 μM.</p>

<p>EFP-IN-1: potent β-lysine derivative, inhibits EFP, slows E. coli growth.</p>

<p>GC-78-HCl is an orally active, non-peptidic SARS-CoV-2 Mpro inhibitor with an enzyme IC50 of 0.19 μM. It exhibits strong anti-coronavirus activity and favorable pharmacokinetic properties.</p>

<p>RmlA-IN-2: Strong RmlA blocker, hinders l-rhamnose synthesis &amp; alters bacterial wall permeability (IC50: 0.303 μM).</p>

<p>RAD51-IN-7 inhibits RAD51 gene, with potential for mitochondrial disorders. (From WO2021164746A1, cmpd 71)</p>

<p>DNA polymerase-IN-6 (Compound 27) exhibits inhibitory activity against DNA polymerase, with EC50 values of 0.33 µM for HCMV, 1.9 µM for HSV-1, 0.76 µM for HSV-2, and 0.066 µM for EBV.</p>

<p>And1 degrader 1 (Compound A15) is a degrader of acidic nucleoplasmic DNA-binding protein 1 (And1) that notably induces degradation of And1 in NSCLC cells. When combined with Olaparib (1 μM), And1 degrader 1 at a concentration of 5 μM effectively inhibits proliferation in A549 and H460 cells. This compound is applicable in cancer research studies.</p>

<p>LpxH-IN-2 (compound 014), a potent inhibitor of LpxH, exhibits antibacterial activity against E. coli.</p>

<p>Atramycin A is an anthraquinone antibiotic with antitumor properties.</p>

<p>ACHN-975 TFA is a selective LpxC inhibitor with a subnanomolar inhibitory. It is against a wide range of gram-negative bacterias with low MIC values (≤1 μg/mL).</p>

<p>VPC-80051 is an hnRNP A1 splicing activity inhibitor that directly interacts with the hnRNP A1 RBD and reduces AR-V7 messenger levels in the 22Rv1 CRPC cell line. VPC-80051 is applicable in prostate cancer research.</p>

<p>KKL-40 is a small-molecule inhibitor that targets the trans-translation process, effectively suppressing methicillin-sensitive and resistant Staphylococcus aureus (S. aureus) and other Gram-positive pathogens, including vancomycin-resistant Enterococcus faecium, Bacillus subtilis, and Streptococcus pyogenes. It works in synergy with the human antimicrobial peptide LL-37 to inhibit S. aureus, but does not show synergistic effects with other antibiotics such as daptomycin, kanamycin, or erythromycin. KKL-40 inhibits trans-translation, an extreme form of recoding, while being non-toxic to HeLa cells.</p>

<p>HIV-1 protease-IN-6 (17d) strongly inhibits HIV-1 protease (IC50: 21 pM, Ki: 4.7 pM) and effectively targets DRV-resistant mutants.</p>

<p>SID 26681509 is a selective inhibitor of cathepsin L (IC50: 56 nM) and blocks Plasmodium falciparum (IC50: 15.4 μM) and Leishmania major (IC50: 12.5 μM).</p>

<p>(E)-Antiviral agent 67 (compound PC6) is a pyrazolone-based antiviral compound that exhibits inhibitory activity against RNA-dependent RNA polymerase.</p>

<p>HCVNS5B polymerase-IN-2 (Compound 298) is an inhibitor of the Ns5b polymerase. It holds potential for research into the treatment of hepatitis C virus (HCV) infections.</p>

<p>CM-728 is an oxazanonaphthoquinone that exhibits cytotoxic and antibacterial properties. It acts as a human peroxidase-1 inhibitor and serves as a source of oxidative stress affecting mitochondrial function.</p>

<p>Jun13296 is an orally active quinoline SARS-CoV-2 papain-like protease inhibitor (IC50 = 0.13 µM, Ki = 8.8 nM). It demonstrates potent inhibitory effects against SARS-CoV-2 variants and Nirmatrelvir-resistant mutants. Jun13296 reduces lung viral titers and prevents lung tissue damage in SARS-CoV-2 infection models.</p>

<p>PKZ18 is an antibiotic that inhibits bacterial growth with a MIC value of 32-64 μg/mL against most Gram-positive bacteria. It suppresses the in vivo transcription and translation of glycyl-tRNA synthetase mRNA. PKZ18 selectively targets stem I specifier loops in Gram-positive bacteria, directly reducing T-box transcription readthrough of associated genes. It prevents codon-anticodon pairing necessary for tRNA binding and is less likely to induce resistance.</p>

<p>JPL is an InhA-cofactor-ligand 3FNG inhibitor and is used for the study of tuberculosis [1].</p>

<p>Antifungal 42 blocks biofilm formation and inhibits C.albicans' CYP51.</p>

<p>InhA-IN-7 (Compound 11), a derivative of Triclocan, shows inhibitory activity against enoyl-acyl carrier protein reductase (InhA) with an IC50 of 96 nM. It effectively inhibits the proliferation of both wildtype and mutant strains of Mycobacterium tuberculosis, exhibiting minimum inhibitory concentrations (MICs) ranging from 19 to 75 μM [1].</p>

<p>GR 122222X is an inhibitor of topoisomerase II.</p>

<p>Xeruborbactam isoboxil is a β-lactamase (beta-lactamase) inhibitor.</p>

<p>Antifungal agent 16 has antimicrobial activity comparable to that of ciprofloxacin and has higher antifungal activity than fluconazole.</p>

<p>NRTT-IN-1 (Compound 1) is an inhibitor of the nucleoside reverse transcriptase translocation (NRTT), effectively blocking HIV DNA synthesis and viral replication.</p>

<p>Antitubercular agent-23 combats Candida albicans (MIC: 1.1 μg/ml) and M. tuberculosis (MIC: 1 μg/ml).</p>

<p>5-Iminodaunorubicin HCl: quinone-modified anthracycline with antitumor properties, induces DNA breaks in cancer cells.</p>

<p>MIV-150 is a nonnucleoside inhibitor of reverse transcriptase (NNRT). MIV-150 also blocking HIV-1 and HIV-2 infections (EC50&lt;1 nM against HIV-1/HIV-2MN).</p>

<p>BPR3P0128, a non-nucleoside RNA-dependent RNA polymerase (RdRp) inhibitor, is effective orally and can inhibit various SARS-CoV-2 variants. It exhibits EC 50 values of 0.62 µM for SARS-CoV-2 and 0.14 µM for HCoV-229E, demonstrating potent anti-pancoronavirus activity at submicromolar concentrations. Additionally, BPR3P0128 displays synergistic antiviral effects when used in combination with Remdesivir [1].</p>

<p>Gallinamide A is a potent inhibitor of cathepsin L with an IC 50 value of 17.6 pM.</p>

<p>HIV-1 inhibitor-13: oral NNRTI, IC50=0.14μM for HIV-1 RT, effective on resistant strains (EC50=2.85-18nM).</p>

<p>LY 215890 is a compound that exhibits potent Gram-negative and Gram-positive antibacterial activity.</p>

<p>Chitinase-IN-5 (8i) blocks OfChi-h (IC50: 0.051 μM), has insecticidal qualities, useful for eco-friendly pest control.</p>

<p>MurA-IN-6 (Compound L16) is a selective MurA inhibitor with an IC50 of 26.63 μM. It exhibits antibacterial activity by inhibiting the function of MurA, a key protein essential for bacterial cell wall synthesis.</p>

<p>Acetomycin, a γ-lactone from S. ramulosus, halts HCT-8 colon and L1210 leukemia cell growth.</p>

<p>GS-9822 is a new LEDGIN inhibitor targeting LEDGF/p75 to alter HIV integration, showing a block-and-lock effect in cells.</p>

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

<p>Antifungal agent 25: broad-spectrum, stable in vivo, effective against Candida albicans, including fluconazole-resistant strains.</p>

<p>RSV-IN-7 (example 253) is a RSV inhibitor ( EC 50 : &lt; 0.4 μΜ) .</p>

<p>Xanthosine-5'-Triphosphate (5'-XTP) trisodium is a nucleotide formed through the deamination of purine bases. It serves as a substrate for inosine triphosphate pyrophosphatase (ITPase).</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>SPR7 is a potent and selective rhodesain inhibitor (Ki: 0.51 nM). SPR7 exhibited antiparasitic effects against T. b. brucei (EC50: 1.65 μM).</p>

<p>MMV03 is an antimalarial compound effective against Plasmodium falciparum, with an EC50 of 0.6 μM.</p>

<p>Antifungal agent 11 has a good antifungal effect.</p>

<p>KPC-2-IN-2 (6c) inhibits KPC-2 enzyme in Klebsiella pneumoniae (Ki 0.038 μM) and boosts cefotaxime in E. coli KPC-2.</p>

<p>Colistin adjuvant-2 is a compound that acts as a potentiation agent for colistin, effectively enhancing its activity against Gram-negative bacteria [1].</p>

<p>Antibacterialagent 262 (compound A23) is a potent antibacterial agent that inhibits the activity of Xanthomonas oryzae pv oryzae. It also disrupts the integrity of bacterial cell membranes by preventing the formation of biofilms of Xanthomonas oryzae pv oryzae.</p>

<p>RECTAS-2.0 is a small molecule designed to correct RNA mis-splicing caused by the GLA c.639+919G&gt;A mutation, intended for research in Fabry disease.</p>

<p>Compound 3d: antitubercular, MIC 0.007 μg/mL vs MTB H37Rv, 1.851 μg/mL vs MDR-MTB 16833, metabolically unstable.</p>

<p>Antibacterial agent 80 (compound 20) has antibacterial activity [1].</p>

<p>SP inhibitor 1 blocks SARS-CoV-2 replication in vitro (0.3250&lt;5.98 μM) and targets SP protein (IC50: 3.26 μM) with antiviral effects.</p>

<p>Squalamine lactate is an aminosterol compound discovered in the tissues of the dogfish shark, with antimicrobial activity.</p>

<p>Cephalosporin C exhibits relatively weak resistance to Gram-positive and Gram-negative bacteria. It is stable against penicillinase, but can be decomposed by cephalosporinase. When hydrolyzed to remove its side chain, it yields 7-amino-cefenoic acid (7-ACA), which is an essential raw material for the production of semisynthetic cephalosporins.</p>

<p>LasR-IN-3 inhibits LasR in Pseudomonas, disrupting its dimer, causing loss of function.</p>

<p>Avibactam sodium dihydrate (NXL-104) is a reversible covalent inhibitor for CTX-M-15 and TEM-1 β-lactamases with IC50s of 5 nM and 8 nM.</p>

<p>EBOV-IN-10 is an orally active inhibitor of the Ebola virus (EBOV) with an EC50 value of 0.19 μM.</p>