Microbiology/Virology

<p>Polθ-IN-7 (example 12) is an inhibitor of DNA polymerase θ (Polθ) with a Ki of 1.27 nM.</p>

<p>5,6-Dihydro-5-azathymidine exhibits activity against both Gram-positive and Gram-negative bacteria, as well as DNA viruses.</p>

<p>Urease -IN-1 is a urease inhibitor (IC50: 2.21±0.45 μM).</p>

<p>PF-07957472 (Compound 4) is an orally effective inhibitor of the SARS-CoV-2 papain-like protease (PLpro). In NHBE cells infected with SARS-CoV-2, it demonstrated cytopathic effects with an EC50 of 13.9 nM. Additionally, PF-07957472 exhibited antiviral activity in a mouse-adapted COVID-19 infection model.</p>

<p>SARS-CoV-2-IN-97 (Compound CO-01) is an inhibitor of the SARS-CoV-2Nsp15 endoribonuclease, exhibiting an IC50 of 53.5 μM. It demonstrates low cytotoxicity in A549-AT cells with an IC50 value of 134 μM.</p>

<p>SARS-CoV-IN-6 (Compound 17) acts as an inhibitor of SARS-CoV-1 and SARS-CoV-2 RdRp, demonstrating an IC50 value of 7.8 μM against SARS-CoV-2 RdRp. This compound reduces the cytopathic effects of single-round infectious particles (SRIP) infected with SARS-CoV-1 and SARS-CoV-2 replicons and inhibits the expression of SARS-CoVN proteins. The EC50 values for SRIP based on SARS-CoV-1 and SARS-CoV-2 replicons are 0.12 µM and 1.47 µM, respectively.</p>

<p>CTSL/CAPN1-IN-2 (Compound 14b) serves as an orally active inhibitor targeting both CTSL and CAPN1, manifesting IC50 values of 6.88 nM for CTSL and 347.6 nM for CAPN1 respectively. This compound not only displays anti-inflammatory attributes but also features favorable pharmacokinetic properties. Moreover, CTSL/CAPN1-IN-2 shows extensive antiviral effects against coronaviruses by inhibiting viral entry [1].</p>

<p>SARS-CoV-2-IN-80 (compound 13), identified as a potent inhibitor of SARS-CoV-2 3CLpro, exhibits an IC50 value of 0.964 µM [1].</p>

<p>DHX9-IN-9 (509) acts as an inhibitor of the RNA helicase DHX9, demonstrating an EC50 of 0.0177 μM in DHX9 cellular target engagement, primarily utilized in cancer research [1].</p>

<p>Antibacterial agent 204 (Compd P2-56-3) enhances the activity of Rifampin (RIF) against Acinetobacter baumannii and Klebsiella pneumoniae by disrupting the outer membrane of A. baumannii. T [1].</p>

<p>HKI12134085 (compound 3), an orally administered nitrobenzothiazinone (BTZ) derivative, demonstrates antibacterial efficacy against Mycobacterium tuberculosis. This compound exhibits significant in vivo inhibitory potency within a BALB/c mouse model of Mycobacterium tuberculosis infection [1].</p>

<p>Pneumolysin-IN-1 (compound PB-3), characterized as a targeted small molecule inhibitor of Pneumolysin (PLY) with an IC50 value of 3.1 µM, acts as a pore-blocking agent and an anti-virulence factor. This compound is useful for researching infections caused by Streptococcus pneumoniae [1].</p>

<p>Uridine 3′,5′-diphosphate (3′,5′-UDP; Compound pUp) serves as a competitive RNase inhibitor [1].</p>

<p>WRN inhibitor 7 (Compound h6), a potent inhibitor of Werner syndrome helicase, demonstrates effective suppression of WRN's helicase and ATPase activities with IC50 values of 9.8 μM and 15.8 μM, respectively. This compound is utilized in the study of microsatellite instable (MSI) cancers [1].</p>

<p>NDM-1 Inhibitor-5 (compound 57) exhibits strong inhibition of NDM-1, characterized by a K i of 2.5 μM. Additionally, it demonstrates synergistic antibacterial effects when combined with meropenem [1].</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>SHEN26 (ATY014) is a potent, orally active RdRp inhibitor with an IC50 of 1.36 μM for SARS-CoV-2. As a 5'-cyclohexanecarboxylate derivative of GS-441524, SHEN26 inhibits viral nucleic acid synthesis, achieving antiviral effects. SHEN26 can be used for COVID-19 research [1] [2].</p>

<p>Antibacterialagent 278 (compound B1) is an antimicrobial agent that exhibits potent inhibitory activity against Gram-positive bacteria.</p>

<p>PAV-104 inhibits the replication of SARS-CoV-2 at a MOI of 0.01. It interacts with the SARS-CoV-2 nucleocapsid (N) and disrupts its oligomerization, thereby preventing particle assembly.</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>Ipronidazole (RO-71554) is an orally effective antiprotozoal agent used to prevent and ameliorate histomoniasis in turkeys, commonly referred to as blackhead disease.</p>

<p>Polθ-IN-5 (Compound 139) is an inhibitor of DNA polymerase theta (Polθ) that exhibits antitumor activity.</p>

<p>PIQ-2 (compound 54) serves as an antiprotozoal agent, displaying potent activity against IP. falciparum 3D7 and B. divergens Rouen, with IC50 values of 9.4 nM and 1.6 nM, respectively.</p>

<p>WRN inhibitor 12 (compound 5) serves as an inhibitor for the WRN helicase.</p>

<p>Polθ-IN-6 (Compound 89) is an inhibitor of DNA polymerase theta (Polθ) and exhibits antitumor activity.</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>

<p>PCNA-IN-1 (Compound 11) is an inhibitor of the PCNA/PIP-box interaction, with an IC50 greater than 50 μM. It is applicable in cancer research.</p>

<p>2-CEES is a mustard gas analogue that only forms DNA monoadducts. It induces centromere amplification in both human and mouse cells and can lead to chromosome instability.</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>SARS-CoV-2-IN-106 (compound 19) is a SARS-CoV-2 papain-like protease inhibitor, displaying IC50 values of 0.44 μM for papain-like proteases and 0.18 μM for viral replication.</p>

<p>N-Nitrosonornicotine, a tobacco-specific nitrosamine, exhibits carcinogenic and mutagenic properties, and is capable of inducing micronuclei in C3A cells. Additionally, N-Nitrosonornicotine can form DNA adducts.</p>

<p>2,5-Di-tert-butyl-1,4-benzoquinone is a potent antibacterial agent found primarily in marine Streptomyces sp. VITVSK1, effective against emerging antibiotic resistance. Additionally, it serves as a powerful inhibitor of RNA polymerase.</p>

<p>SARS-CoV-2 Mpro-IN-34 (Compound 26) acts as an inhibitor of SARS-CoV-2 Mpro with an IC50 of 6 nM. It also inhibits OC43 Mpro, demonstrating an IC50 of 33 nM. Furthermore, this compound exhibits antiviral activity in Vero E6 cells infected with SARS-CoV-2, with an EC50 of 0.103 μM.</p>

<p>Cefamandole (lithium), a second-generation broad-spectrum cephalosporin antibiotic, exhibits antimicrobial activity. Upon metabolism in the body, it releases free NMTT, which can lead to hypoprothrombinemia.</p>

<p>Cilastatin ammonium salt is an antibiotic that is particularly effective against Gram-positive cocci, with a half-life of 3-4 hours.</p>

<p>5-Methylcytosine hydrochloride plays a critical role in regulating gene expression, promoting genomic imprinting, and inhibiting transposon factors. It is also closely associated with translation fidelity and tRNA recognition.</p>

<p>Pyriftalid is a novel insecticide known for its potent inhibitory activity against a variety of pests. It is widely utilized in agriculture to effectively manage crop pests, thereby enhancing both the yield and quality of crops. Additionally, research is exploring the use of Pyriftalid in boosting plant resistance to pests and diseases.</p>

<p>Lentiginosine is a selective amyloglucosidase inhibitor.</p>

<p>Benzisothiazolone is an isothiazolinone fungicide that demonstrates growth inhibitory activity against Escherichia coli ATCC 8739 and yeast NCYC 1354. It is utilized in studies investigating growth inhibition models.</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>Apalcillin (PC-904) combined with Ro 48-1220 (a penicillin sulfone β-lactamase inhibitor) exhibits broad-spectrum activity against Gram-negative aerobic and anaerobic bacteria, excluding Klebsiella acid-producing strains. This combination shows strong efficacy against β-lactamase-producing Moraxella catarrhalis, Haemophilus influenzae, and Neisseria gonorrhoeae with an effective MIC of 11 μg/mL. Additionally, it inhibits Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter at low MICs (0.25 to 4 μg/mL). However, it has limited efficacy against oxacillin-resistant staphylococci and some Gram-positive bacteria. Apalcillin/Ro 48-1220's effectiveness against certain extended-spectrum β-lactamase-producing Escherichia coli is comparable to piperacillin/tazobactam, though it is less effective against SHV-type β-lactamases.</p>

<p>Valopicitabine is an effective prodrug of the effective anti-HCV drug 2'-C-methylcytidine and can be used as a promising antiviral drug for the study of chronic</p>

<p>MBL-IN-5 is an inhibitor of metallo-β-lactamase (MBL). It effectively suppresses three clinically significant B1 subfamily MBLs: NDM-1, VIM-1, and IMP-1 with IC50 values of 0.05 nM, 14 nM, and 21 nM respectively. MBL-IN-5 notably enhances the efficacy of carbapenem antibiotics against MBL-producing clinical strains and, when combined with IPM antibiotics, significantly reduces bacterial load in a thigh infection model.</p>

<p>NIP-22c, a novel inhibitor of coronavirus 3CL pro, exhibits antiviral activity [1]. The compound's EC50 values are 4.6 μM for Verona, 1.1 μM for Calu3, 0.1 μM for Caco2, and 0.6 μM for HBTEC-ALI.</p>

<p>Antibacterial Agent 172 (Compound 6a), a &lt;i&gt;Clostridioides difficile (Cd) SpoVD inhibitor with an IC50 value of 89 nM, effectively inhibits the sporulation of Clostridioides difficile. It is useful for research on bacterial infections [1].</p>

<p>Compound 174 (Compound 5g), an antibacterial agent, exhibits potent anti-infective properties in vivo along with appreciable pharmacokinetic profiles. This highly active substance demonstrates favorable biofilm removal capabilities, low hemolysis, and acceptable mammalian cell toxicity [1].</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>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>JPL is an InhA-cofactor-ligand 3FNG inhibitor and is used for the study of tuberculosis [1].</p>

<p>HIV-1 inhibitor-14: potent, broad HIV-1 RT inhibitor. IC50=0.14μM. Effective against wild-type and resistant strains, EC50=5.79-28.3nM.</p>

<p>OPC-167832: oral dprE1 inhibitor, IC50 0.258 μM, anti-tuberculosis, for Mycobacterium tuberculosis research.</p>

<p>L-2'-Fd4C is an L-nucleoside analogue with both anti-human immunodeficiency virus (HIV) and anti-hepatitis B virus (HBV) activity [1].</p>

<p>Antibacterial agent 88 is an effective antibacterial agent against B. subtilis (MIC: 4 μg/ml) with MIC values of ≤0.0156 μg/mL for MRSA, MRSE and S. aureus.</p>

<p>Antifungal agent 43 inhibits biofilms with low toxicity to human cancer cells.</p>

<p>Antiviralagent 67 (compound PC6) is an inhibitor of DENVNS5 (RNA-dependent RNA polymerase) with a Ki value of 1.12 nM.</p>

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

<p>Asukamycin, from S. nodosus asukaensis, is a polyketide antibiotic inhibiting tumor cells by activating caspases 8 and 3.</p>

<p>RAD51-IN-6, a potent RAD51 gene inhibitor, may help research mitochondrial disorders. (WO2021164746A1, cmpd 23)</p>

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

<p>Compd 3b: anti-trypanosomal, IC50 0.51 μM (NINOA), 3.06 μM (INC-5), also combats T. gondii.</p>

<p>PfPKG-IN-1, an imidazole-based inhibitor, targets the Plasmodium falciparum cyclic guanosine monophosphate-dependent protein kinase (PfPKG).</p>

<p>Fenbenicillin (Phenbenicillin) potassium is a semi-synthetic penicillin with antibacterial spectrum activity.</p>

<p>BRD-4592 is an allosteric inhibitor targeting tryptophan synthase (TrpAB) of Mycobacterium tuberculosis. It binds at the α-β subunit interface of TrpAB, with an IC50 of 70.9 nM for the α subunit and 22.6 nM for the β subunit.</p>

<p>HT1171 is a potent and selective inhibitor of the Mycobacterium tuberculosis proteasome. It exhibits strong antitubercular activity against Mycobacterium tuberculosis H37Rv, with a MIC90 of 2 μg/mL and MIC of 4 μg/mL. At a concentration of 100 μM, HT1171 shows an inhibition rate of 53.8% against normal human liver cells (L02). HT1171 is applicable in antituberculosis drug research.</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>Antibacterialagent 261 (compound 43) is a potent inhibitor of the peptide deformylase (PDF) enzyme, demonstrating IC50 values of 2.5 nM against Staphylococcus aureus (S. aureus) and 10.6 nM against Escherichia coli (E. coli).</p>

<p>BM635 hydrochloride, an MmpL3 inhibitor, strongly blocks Divergent bacteriophage H37Rv (MIC50: 0.08 μM), with doubled in vivo potency.</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>ZINC000104379474 is a compound that targets SARS-CoV-2 endoribonuclease.</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>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>Quorum sensing-IN-9 (Compound 7d) inhibits quorum sensing in Pseudomonas aeruginosa by binding to the PqsR protein. It suppresses the expression of quorum sensing system-related genes lasB, rhlA, and pqsA, thereby preventing the production of virulence factors elastase, pyocyanin, and rhamnolipid. Quorum sensing-IN-9 disrupts the motility of P. aeruginosa, inhibits biofilm formation, and reduces the bacterium's virulence and pathogenicity. Additionally, it exhibits anti-infective activity in the Galleria mellonella larval model.</p>

<p>Pibrozelesin, a water-soluble duocarmycin B2 derivative, binds AT-rich DNA, blocking replication and inducing cell death.</p>

<p>CDA-IN-1 (Compound vs#2-1) is an inhibitor of chitin deacetylase (CDA) that exhibits antifungal activity. By inhibiting fungal CDA activity, it activates plant immune responses and leads to the accumulation of reactive oxygen species (ROS), hindering fungal growth. At a concentration of 100 μM, CDA-IN-1 achieves inhibition rates of 86.9% on P. xanthii's PxCDA1 and 74.5% on PxCDA2. CDA-IN-1 is applicable in research on fungal plant diseases, such as cucumber powdery mildew and tomato gray mold.</p>

<p>Antibacterial agent 76 (compound 9) is a potent antibacterial agent.</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>HBV-IN-12: strong HBsAg &amp; HBV DNA inhibitor; EC50 0.001-0.05 μM &amp; 0.001-0.02 μM respectively. (WO2021204252A1)</p>

<p>Glutamate-5-kinase-IN-1 is a potent G5K inhibitor with a 4.1 μM MIC, showing promise in anti-TB research.</p>

<p>Benzohydroxamic acid (BHA) is a chitin deacetylase (CDA) inhibitor with notable antifungal properties. It displays Ki values of 8.31 μM against Verticillium dahliae CDA and 9.83 μM against Puccinia striiformis f. sp. tritici CDA. BHA can restore the defense responses in infected host plants by upregulating the expression of defense-related genes, thereby reducing fungal growth and proliferation within the plants. It is applicable in the research of agricultural fungal diseases, such as cotton wilt and wheat stripe rust, caused by pathogens like Verticillium dahliae and Puccinia striiformis.</p>

<p>RAD51-IN-5 blocks RAD51; may aid mitochondrial disorder research. (WO2021164746A1, cmpd 3)</p>

<p>AK-968-11563024 is an inhibitor targeting marine V. vulnificus NAT [(VIBVN)NAT] with an IC50 value of 18.86 µM. In V. vulnificus, NAT (aromatic amine N-acetyltransferase) plays a role in drug metabolism, contributing to drug resistance. Thus, AK-968-11563024 can be used for research related to drug tolerance.</p>

<p>K13787 is an acetohydroxy acid synthase (AHAS) inhibitor with antibacterial properties. It exhibits antimicrobial activity against various non-tuberculous mycobacteria (NTM) as well as clarithromycin (CLR) resistant strains.</p>

<p>RAD51-IN-7 inhibits RAD51 gene, with potential for mitochondrial disorders. (From WO2021164746A1, cmpd 71)</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>Antitubercular agent-15 (5n): low toxicity, fights M. tuberculosis strains; MIC90 values range 0.73-18.8 μg/mL.</p>

<p>L 689065 is a 5-lipoxygenase inhibitor.</p>

<p>Amicoumacin A has antibacterial activity. It also strongly suppresses inflammatory and ulcer activity.</p>

<p>MDL-860 is a broad-spectrum antiviral compound targeting small RNA viruses and exhibits low cytotoxicity to human cells. MDL-860 is useful for research into viral infections.</p>

<p>Chitin synthase inhibitor 8 is a chitin synthase (CHS) inhibitor with broad-spectrum antifungal effects that can be used in studies related to fungal infections</p>

<p>KL-50, a selective toxin, effectively targets tumors deficient in the DNA repair protein O6-methylguanine-DNA-methyltransferase (MGMT), which corrects O6-alkylguanine lesions. This compound induces both DNA damage response pathways and cell cycle arrest in MGMT-deficient cells, regardless of mismatch repair (MMR) status. KL-50 shows promise in the study of brain tumors lacking MGMT.</p>

<p>ZLM-66: Doravirine analog, HIV-1 NNRTI inhibitor, IC50: 41nM, EC50: HIV-1 13nM, cIAP1 0.32nM; useful in AIDS research.</p>

<p>Chitinase-IN-4 (compound 8f) is a potent and selective inhibitor of OfChi-h with an IC50 value of 0.1 μM and good insecticidal activity.</p>

<p>Antitumor agent-74, a quinazoline derivative, inhibits DNA, arrests cell cycle, and induces apoptosis with agent-75.</p>

<p>9-tert-Butyldoxycycline exhibits immunomodulatory activity by altering the polarization state of polymorphonuclear neutrophils and ameliorating inflammatory responses in ischemia-reperfusion injury models. Additionally, 9-tert-Butyldoxycycline serves as a ligand for the "Tet-On" inducible gene expression system.</p>

<p>Compound 5q is a potent antitubercular with low MIC90 values (0.40-23.51 μg/mL) against M. tuberculosis strains, showing minimal cytotoxicity.</p>

<p>Cefclidin (Cefclidine) is a cephalosporin compound.</p>

<p>Bersiporocin is a novel prolyl-tRNA synthetase (PRS) inhibitor that exerts antifibrotic effects through downregulation of collagen synthesis in IPF.</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>Calpain Inhibitor-2, lipophilic, inhibits calpain; shows anti-proliferative effects on melanoma, PC-3 cells; blocks 80% DU-145 cell invasion.</p>