Microbiologie/Virologie

GR 122222X is an inhibitor of topoisomerase II.

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.

RNase L ligand 3 is an RNase L ligand employed in the synthesis of F3-PEG8-RiboTAC.

DNDI-8219 is an antitubercular agent. It has potent antileishmanial effects.

MA220607 is an antibacterial agent characterized by low hemolytic toxicity and a dual-target mechanism of action (MOA). It promotes FtsZ protein polymerization, increases bacterial membrane permeability, and inhibits biofilm formation. The resistance rate of MA220607 is low, with MICs against Gram-positive bacteria and Gram-negative bacteria ranging from 0.062-2 μg/mL and 0.5-4 μg/mL, respectively [1].

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].

Griseofulvic Acid ((±)-Griseofulvic acid) is a metabolite of the antifungal agent Griseofulvin. It induces protein aggregation and tubulin polymerization in cell-free assays.

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

SARS-CoV-2 Mpro-IN-31 (Compound 18) is an inhibitor of SARS-CoV-2 MPro with an IC50 of 11 nM. Additionally, this compound effectively inhibits the enzymatic activity of the cysteine proteases cathepsin B and cathepsin L, with IC50 values of 24 nM and 1.8 nM, respectively.

Ipronidazole (RO-71554) is an orally effective antiprotozoal agent used to prevent and ameliorate histomoniasis in turkeys, commonly referred to as blackhead disease.

CYP51-IN-14 (compound 1n), a derivative of Fluconazole, functions as an effective antifungal agent. This compound inhibits Microsporum gypseum and Candida albicans with a minimum inhibitory concentration (MIC80) of 1 μg/mL.

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

Antibacterial agent 76 (compound 9) is a potent antibacterial agent.

Metesind Glucuronate is an antineoplastic. It also is a specific thymidylate synthase inhibitor.

AN-12-H5 is an anti-enteroviral compound that targets the replication process of PV and EV71 viruses.

G092 is a potent inhibitor of MsbA. MsbA is an ABC transporter protein. G092 has potential for antibacterial drug research.

EFdA-TP tetrasodium is a potent HIV-1 inhibitor that blocks DNA synthesis as an ICT or DCT.

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>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>

MraY-IN-2 (compound 6) is an effective inhibitor of bacterial transposase MraY (IC50=4.5 μ M), and can be used for antibacterial research.

Gln-AMS (TFA) is a type Ia amido-tRNA synthetase (AARS) inhibitor with a Ki value of 1.32 μM for glutaminyl-tRNA synthetase.

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

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.

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

NITD-688 is a pan-serotype inhibitor targeting the dengue virus NS4B protein, effective through oral administration.

NBTIs-IN-5 inhibits Mycobacterium abscessus DNA with IC50 1.5μM, halts growth at MIC90 0.4μM.

Anti-MRSA agent 23 (compound 11) is a potent agent against methicillin-resistant Staphylococcus aureus. This compound exhibits both antibacterial and antibiofilm properties. It facilitates the healing and reconstruction of MRSA-infected skin wounds by reducing bacterial load, alleviating inflammation, and promoting angiogenesis.

ACSS2-IN-1, a potent ACSS2 inhibitor, has IC50 0.01-<1 nM; useful in cancer research.

ddCTP trisodium, an HIV reverse transcriptase target, aids AIDS research and DNA sequencing as a ddNTP.

ZK-316 is a potent and broad-spectrum NNRTI inhibitor with an EC50 range of 0.99 to 75.1 nM. It is applicable for HIV research.

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

<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>

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.

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

Isazofos is a broad-spectrum organophosphate insecticide and nematicide effective in controlling a variety of lawn pests, such as nematodes (Radopholus similis). It also demonstrates efficacy in managing rice gall midge.

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

AYK004-C1 is a TLR agonist used in the formulation of immunological adjuvants.

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).

Flutimide: Endonuclease inhibitor, IC50 = 3μM, for research on acute respiratory diseases like influenza.

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.

Antibacterial agent 68 targets drug-resistant E. coli at 0.007 mM with low cytotoxicity.

Antimalarial agent 2 is an orally active, novel antimalarial agent that exhibits rapid in vitro killing effects.

MB076 is an innovative heterocyclic triazole designed with enhanced plasma stability. It effectively inhibits seven distinct Class C Acinetobacter-derived cephalosporinases (ADCs) β-lactamase variants with K i values less than 1 μM. Additionally, MB076 demonstrates a synergistic effect when combined with various cephalosporins to restore pBCSK(−) susceptibility [1].

AVE-1330A sodium is a beta-Lactamase inhibitor.

Antibacterial agent 113 targets multiple bacteria including P. aeruginosa and E. coli, showing efficacy at MIC 15625 μM.

Thiolactomycin is a novel reversible dual inhibitor of D-amino acid oxidase (DAO) and D-Aspartate oxidase (DDO).

<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>

Finafloxacin is a pH-activated fluoroquinolone, most effective at pH 5.0-6.0, targeting bacterial topoisomerases, used for UTIs and H. pylori infections.

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.

Artefenomel (OZ439) is an orally active anti-malarial ozone analog with antiviral activity for the study of SARS-CoV-2 infections and malaria infections.

Antileishmanial agent-4, a ribonucleoside analogue, targets L.infantum and T.cruzi with EC50s of 0.68 μM and 0.83 μM.

Cap-dependent endonuclease-IN-14 hinders CEN and could treat influenza virus infections. (Patent CN113620948A, compound 1-c).

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.

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.

Antileishmanial agent-4, a ribonucleoside analogue, functions as an antileishmanial agent [1].

Antitrypanosal agent 5 is a selective anti-trypanosomal agent that acts on T. brucei (IC50: 1 nM) and HEK293 cells (IC50: 483.3 μM).

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

20S Proteasome-IN-4: brain-penetrant, parasite-specific, oral, inhibits T.b. brucei proteasome (IC50: 6.3nM), for HAT research.

Faldaprevir sodium: HCV treatment, inhibits NS3/NS4A protease, P-glycoprotein, CYP3A4, UGT1A1.

4-Chloropyridine acts as an inhibitor of Nicotinamide N-methyltransferase (NNMT). Serving as a substrate for NNMT, this compound enhances the electrophilicity at the C4 position through methylation of the pyridine nitrogen. This modification facilitates an aromatic nucleophilic substitution reaction with the non-catalytic cysteine (C159) in NNMT, ultimately leading to suicidal activity inhibition of the enzyme. 4-Chloropyridine is a promising candidate for the development of activity-based probes targeting NNMT functions.

Compound 112: Powerful antibacterial, MIC 1250 μM against B. subtilis, E. coli, E. faecalis, S. typhimurium, S. aureus; also an HIV-1 antibody.

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

Nikkomycin Z (Nikkomycin Z from Streptomyces tendae) is a competitive chitin synthase inhibitor.It inhibitor of the growth of filamentous fungi, insects,

Antibacterialagent 281 (Compound 95,186) effectively inhibits the growth of GAS by binding to the ligand-binding pocket of SPs0871, competing with the ligand. It exhibits concentration-dependent growth inhibition against Streptococcus pyogenes (S. pyogenes).

RmlA-IN-2: Strong RmlA blocker, hinders l-rhamnose synthesis & alters bacterial wall permeability (IC50: 0.303 μM).

3-Epiquinine is a Quinidine stereoisomer, used in malaria, antiarrhythmic, inhibits P450db, and blocks K+ channels, IC50: 19.9 μM.

<p>Bersiporocin is a novel prolyl-tRNA synthetase (PRS) inhibitor that exerts antifibrotic effects through downregulation of collagen synthesis in IPF.</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.

MBX-1162, a bis-indole compound, has demonstrated unique substrate specificity related to MepA and MepR in studies investigating its resistance mechanisms in Staphylococcus aureus. It has not shown cross-resistance with related compounds.

AB25583 is a small molecule inhibitor of Polθ helicase (Polθ-hel) with an IC50 of 6 nM. It selectively kills cells deficient in BRCA1/2 and synergizes with Olaparib in cancer cells harboring pathogenic BRCA1/2 mutations. AB25583 can be utilized in tumor research.

Antifungal agent 43 inhibits biofilms with low toxicity to human cancer cells.

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.

DPC 684 is a potent and selective HIV-1 protease inhibitor with an IC90 of 5.7-40 nM and a Ki of 0.021 nM. It competitively inhibits HIV-1 protease, preventing viral polyprotein cleavage. Compared to cellular proteases, DPC 684 shows high selectivity for retroviral proteases. The compound exhibits low protein binding and offers broad-spectrum inhibition against various wild-type and mutant HIV-1 proteases, with an IC90 of 1.9-6.3 nM. DPC 684 is significant for HIV research.

SMCypIC31, a non-peptide cyclophilin inhibitor, blocks PPIase at 0.1 μM IC50 and fights various HCV genotypes (EC50: 1.20-7.76 μM).

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

844-TFM, a NBTI DNA gyrase blocker, IC50: 1.5 μM, kills Mycobacterium abscessus.

Isopyrazam, a plant protection product, exhibits potent antifungal activity. When applied to crops, it effectively inhibits the growth of various plant pathogenic fungi, significantly enhancing both the yield and quality of the crops. This compound demonstrates exceptional disease resistance capabilities in agricultural applications.

Inactive enantiomer of Sofosbuvir, used for chronic hepatitis C; lacks reported biological activity.

<p>iPAF1C is a powerful inhibitor of the polymerase-associated factor 1 complex (PAF1C) and exhibits anti-HIV activity [1].</p>

Eprociclovir Na (A-5021) is 15x stronger than acyclovir at inhibiting herpesviruses, showing promise for EHV1 and herpetic keratitis treatment.

HIV-1 Inhibitor-61 (2c) serves as a potent inhibitor of HIV-1 reverse transcriptase, exhibiting an EC50 value of 0.07 nM in NL4-3 wt MT-4 cells [1].

Antimicrobial Agent-29 (Compound C35) influences the interaction between human hemoglobin and the Staphylococcus aureus IsdB hemophore. This compound facilitates the identification of IsdB:Hb PPI inhibitors [1].

Pyrromycin is a monosaccharide anthracycline which can be used to inhibit cellular RNA synthesis.

DHFS-IN-1 (Compound 3) is an inhibitor of dihydrofolate synthetase (DHFS) with an IC50 of 2.6 μM. It is applicable for research into infectious diseases related to bacterial folate synthesis.

3′-Amino-2′,3′-dideoxy-CTP is an analog of nucleoside triphosphates. It selectively inhibits DNA polymerase β.

DL-2-Aminopimelic Acid acts as a weak agonist for glutamate receptors and also reduces the sensitivity of leech glutamate receptors to glutamate.

Ambelline has antitumor activity.

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.

7-APRA is a semisynthetic intermediate of the cephalosporin class of antibiotics. It exhibits antibacterial activity and is primarily used in the synthesis of other cephalosporin antibiotics, such as Cefaclor and Cefprozil.

BDM91288, an orally active AcrB efflux pump inhibitor of pyridinium piperazine, enhances the in vivo efficacy of levofloxacin in treating Klebsiella pneumoniae pulmonary infection in mouse models [1].

(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>Enpatoran hydrochloride (M5049 hydrochloride) is a TLR7/8 inhibitor with antiviral activity that is used in the study of autoimmune diseases.</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.

WRN inhibitor 13 is an inhibitor of the WRN helicase with a pIC50 value ranging from 6 to 7.

<p>CCF0058981: noncovalent inhibitor for SARS-CoV-2 &amp; -1 proteases; IC50s: 68 nM (SC2) &amp; 19 nM (SC1). Potential COVID-19 research use.</p>

HRO761 is a potent Werne r syndrome RecQ DNA deconjugase (WRN) inhibitor that can be used to study cancers such as colon and stomach cancer.

Tigemonam is a monobactam, a novel orally administered monobactam that protects against gram-negative aerobic bacterial pathogens. Cost-effective and quality-assured.

<p>LeuRS-IN-1 hydrochloride is a Mycobacterium tuberculosis leucyl-tRNA synthetase inhibitor with antileukemic activity and antimalarial activity.</p>

CTPS1-IN-1 is a cytidine-5′ triphosphate synthase 1 (CTPS1) inhibitor with potential antitumor activity and can be used to study autoimmune diseases.

Vaniprevir is a competitive HCV NS3/4A protease inhibitor, an antiviral(hepatitis C virus) drug that acts directly and blocks the viral replication process.