DNA gyrase inhibitor EN-7 (EN-7) is a potent bacterial DNA gyrase inhibitor, is active against pathogenic species that are resistant to ciprofloxacin and other clinically important antibiotics.EN-7 inhibited growth of the wild-type strain (S. aureus) with MIC 1 μM.Strains containing GyrA A34T (mut-3 and mut-9), GyrA P219Q (mut-6), and GyrB K417E (mut-1, mut-2, mut-4, and mut-5) exhibited moderate resistance, with MICs of either 4 or 8 μM.EN-7 inhibited sporulation pathway in the bacterial genus Streptomyces.

DMA-135 (DMA135) is a RNA-biased small molecule binds to the EV71 SLII IRES domain (Kd=520 nM), dose-dependently (IC50=7.54 uM) inhibits EV-71 viral translation and replication.DMA-135 inhibits EV71 replication by attenuating IRES-dependent translation at dosages of relatively low cellular toxicity.DMA-135 changes the local and global structure of the EV71 SLII IRES domain.DMA-135 allosterically stabilizes a AUF1 (cellular protein)-SLII-(DMA-135) ternary complex.

DMA-135 (DMA135) is a RNA-biased small molecule binds to the EV71 SLII IRES domain (Kd=520 nM), dose-dependently (IC50=7.54 uM) inhibits EV-71 viral translation and replication.DMA-135 inhibits EV71 replication by attenuating IRES-dependent translation at dosages of relatively low cellular toxicity.DMA-135 changes the local and global structure of the EV71 SLII IRES domain.DMA-135 allosterically stabilizes a AUF1 (cellular protein)-SLII-(DMA-135) ternary complex.

Dichlorcyclizine (DCCZ) is a potent, small molecule HCV fusion inhibitor, also inhibits SARS-CoV and SARS-CoV-2 S-mediated infection in MA104 cells with EC50 of 9.92 and 4.53 uM, respectively.

CTN1122 (CTN-1122) is a potent, selective Leishmaniacasein kinase 1 isoform 2 (CK1.2, L-CK1.2) with IC50 of 0.72 uM (LmCK1) and 0.8 uM (amastigotes L. major), antileishmanial compound.

CTCB-405 (CTCB405) is a small molecule allosteric inhibitor of T. brucei phosphofructokinase (TbPFK) with IC50 of 0.18 uM, ITC Kd of 92 nM, no significant inhibition of human PFKs.CTCB-405 demonstrated in vitro parasite killing potency of the bloodstream form of T. brucei strain Lister 427 (EC50=0.37 uM).CTCB-405 (50, 100 mg/kg) clear parasites in a stage 1 model of HAT infection with 1-day oral dosing and show reduction of parasitaemia in the brain in a pleiomorphic model.

COR588 is a second-generation small-molecule lysine-gingipain (Kgp, gingipain K) inhibitor with novel structure and improved pharmacologic and safety profile prioritized for Alzheimer’s development.

COR388 (Atuzaginstat) is an orally bioavailable, brain penetrant small-molecule that irreversibly inhibits lysine-gingipain (Kgp, gingipain K) with Ki of <0.01 nM.COR388 blocks the activity of gingipains, a type of toxic protein made by the bacteria Porphyromonas gingivalis ( P. gingivalis ).COR388 reduced the bacterial load of an established P. gingivalis brain infection, blocked Aβ1-42 production, reduced neuroinflammation, and rescued neurons in the hippocampus.

Ciapavir (SBI-0953294, cIAP1 antagonist for viral reactivation) is a bivalent, next-generation, Smac mimetic and antagonist of cIAP1 as latency-reversing agent (LRA), specifically and potently promote HIV-1 latency reversal activity both in vivo.Ciapavir's latency reversal activity is dependent on the NIK-dependent NF-κB signaling.Ciapavir exhibits substantially greater potency and efficacy as an LRA, inducing comparable levels of latency reversal at concentrations 10- to 1,000-fold lower than the first-generation molecule SBI-0637142, without an increase in cytotoxicity.Ciapavir does not trigger cytokine release or T cell activation.Ciapavir is capable of increasing latent HIV-1 expression in ART-treated BLT mice in vivo and may therefore prove useful in "shock and kill" approaches to HIV-1 cure.

CBS1194 is a novel specific fusion inhibitor for group 2 influenza viruses, inhibits IAVs bearing group 2 HAs (pseudo-H7, EC50=0.25 uM).CBS1194 displays no inhibition against both pseudo-H5 and pseudo-Lassa.CBS1194 exhibitss potency agianst group II influenza viruses influenza A/rhea/North Carolina/1993 (H7N1) and A/Hong Kong/1/1968 (H3N2) with EC59 of 3.17 and 1.60 uM, respectively.CBS1194 displays no inhibitory activity against group 1 influenza viruses, including A/Puerto Rico/8/1934 (H1N1) and A/Viet Nam/1203/04 (H5N1).CBS1194 acts at an early stage of viral infection, inhibits viral HA mediated hemolysis, and prevents the low pH-induced conformational change of HA.The substitutions K1172N and T301A but not D71N to confer resistance to CBS1194.

CBR417 (CBR-417) is a potent and selective antiwolbachial activity compound (Anti-Wolbachia wMel In vitro HCI cell-based assay IC50=21 nM, IC90=1640 nM).CBR417 demonstrates potent antiwolbachial activity was confirmed in L. sigmodontis, Brugia malayi, and Onchocerca ochengi in vivo preclinical models of filarial disease.CBR417 demonstrates in vitro selectivity against Loa loa (a safety concern in endemic areas).

Burkfloxacin (BFX) is a fluoroquinolone analog that potently inhibits growth of intracellular Burkholderia.Burkfloxacin is active against other gram-negative organisms in vitro, showing similar potency to the widely used fluoroquinolone, ciprofloxacin (Cip), against Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853.Burkfloxacin near-completely inhibits plaque formation by Bt and Bp at concentration of 0.5 uM.Burkfloxacin functions as a canonical fluoroquinolone by inhibiting the negative DNA supercoiling activity of E. coli DNA gyrase.Treatment with Burkfloxacin was significantly more effective than ceftazidime, the current antibiotic of choice, for improving survival and decreasing bacterial counts in major organs in a murine model of fulminant respiratory melioidosis.

BLI-489 is a bicyclic penem inhibitor that inhibits class A, C, and D beta-lactamases with synergistic effects with piperacillin; The combination of piperacillin-BLI-489 demonstrated improved activity compared to that of piperacillin-tazobactam against the problematic extended-spectrum beta-lactamase- and AmpC-expressing strains.

BDM88855 is a novel allosteric efflux-pump inhibitor that potentiate antibiotic activity in E. coli through inhibition of its primary RND transporter, AcrAB-TolC.BDM88855 binds to a unique site on the transmembrane domain of the AcrB L protomer, lined by key catalytic residues involved in proton relay, boost antibiotic activity in E. coli by inhibiting the AcrAB-TolC efflux pump.

BDM88855 Hcl is a novel allosteric efflux-pump inhibitor that potentiate antibiotic activity in E. coli through inhibition of its primary RND transporter, AcrAB-TolC.BDM88855 binds to a unique site on the transmembrane domain of the AcrB L protomer, lined by key catalytic residues involved in proton relay, boost antibiotic activity in E. coli by inhibiting the AcrAB-TolC efflux pump.

Azoffluxin (CMLD012336) is a bis-benzodioxolylindolinone that synergizes with fluconazole against C. auris through the inhibition of efflux pump Cdr1, thus increasing intracellular fluconazole levels.Azoffluxin increases intracellular accumulation of fluconazole (FLC) by inhibiting Cdr1-mediated efflux in C. auris.Azoffluxin potentiates intracellular acting compounds against C. auris, to a similar degree as deletion of CDR1.Azoffluxin is active against diverse C. auris strains, azoffluxin potentiated fluconazole in multiple isolates from three of the four major clades. The clade III isolates from South Africa were the exception.Azoffluxin enhances fluconazole (FLC) activity against azole-resistant C. albicans isolates.Azoffluxin not only enhanced fluconazole activity but also reduced fungal burden by ~1000-fold as a single agent in mice infected with drug-resistant C. auris.

ARN-75041 (ARN75041) is a potent, small molecule fusion inhibitor of arenavirus, inhibits pseudotyped entry of pGTOV and pCHAPV with EC50 of 1.7 and 15.3 nM, respectively. ARN-75041 demonstrated sub-nanomolar against native replicative LASV (LASV EC90<0.3 nM) and JUNV (EC90=6.2 nM).ARN-75041 also potently inhibits mutant T434I pTCRV variant with EC50 of 29 nM.ARN-75041 dramatically improved survival outcome and potently inhibited TCRV replication in serum and various tissues at doses of 10 and 35 mg/kg, provided highly significant post-exposure protection in mice against TCRV infection.

ARN-75039 (ARN75039) is a potent, small molecule fusion inhibitor of arenavirus, inhibits pseudotyped entry of pGTOV and pCHAPV with EC50 of 0.13 and 4.3 nM, respectively.ARN-75039 demonstrated sub-nanomolar EC50 activity against pTCRV that further translated to native wild-and NWAs, including LASV, JUNV and MACV, in pseudotyped virus assays and against native replicative LASV and JUNV.ARN-75039 also potently inhibits mutant T434I pTCRV variant with EC50 of 29 nM.ARN-75039 dramatically improved survival outcome and potently inhibited TCRV replication in serum and various tissues at doses of 10 and 35 mg/kg, provided highly significant post-exposure protection in mice against TCRV infection.

Antimicrobial peptide BING (IRIILRAQGALKI) is a thermostable 13-residue peptide that targets bacterial envelope stress response by suppressing cpxR expression in Gram-negative bacteria.BING downregulates efflux pump components and synergises the effect of antibiotics, and suppresses the development of antibiotic resistance.BING downregulated the expression of efflux pump components mexB, mexY and oprM in P. aeruginosa and significantly synergised the toxicity of antibiotics towards these bacteria.

AN12855 (AN-12855) is potent, cofactor-independent M. tuberculosis InhA inhibitor, binds to and inhibits InhA with IC50 of 0.03 uM, shows potent activity against whole-cell M. tuberculosis H37Rv with IC90 of 0.09 uM; AN12855 demonstrates potent activity against drug-susceptible and drug-resistant strains of M. tuberculosis, exhibits comparable efficacy to the frontline antitubercular drug isoniazid (INH) in both acute and chronic models of TB infection with a lower potential for resistance development and shows in vitro activity against conventional KatG-mediated INH-resistant M. tuberculosis.

Amphihevir is a potent, selective HCV NS4B inhibitor with EC50 of 0.34 and 1.97 nM against the GT1a (H77) and GT1b replicon in luciferase assays.Amphihevir shows weaker acitivity against GT2a (JFH-1) (EC50=186 nM).Amphihevir shows EC50 3.13 nM and 18.16 nM with 100% human serum against GT1a and GT1b replicons using HCV-1b replicon cells test.Amphihevir reduced replicon RNA by nearly 6,300-fold (3.8 log10) at a concentration 25-fold greater than the EC90 (300 nM).Amphihevir was found to be inactive against other viruses, human kinases, and GPCRs, which implies its good selectivity.Amphihevir has good oral bioavailability and appropriate T1/2 in rats and dogs, showed good safety profiles in rats and dogs.Amphihevir is the first reported NS4B inhibitor that has advanced to clinical trials.

ACHN-975 (ACHN975) is a potent bacterial LpxC inhibitor with IC50 of 0.68 nM (P. aeruginosa LpxC); ACHN-975 is potent against the P. aeruginosa isolates with MIC50 of 0.06 ug/mL and MIC90 of 0.25 ug/mL. ACHN-975 demonstrated in a neutropenic mouse thigh model with P. aeruginosa ATCC 27853.

ACAi-028 is a small molecule inhibiting HIV-1 replication (EC50=0.55 uM) that targets a hydrophobic pocket in the N-terminal domain of capsid (CA-NTD).ACAi-028 binds directly and noncovalently to HIV-1 capsid monomer.ACAi-028 inhibits the early stage of the HIV-1 life cycle and does not affect the late stage, also prevents multiple-round HIV-1 infection using HIV-1 strains (HIV-1NL4-3 and HIV-1LAI), except for HIV-2 strain (HIV-2ROD).ACAi-028 inhibits the replication of various types of HIV-1 strains (HIV-1104pre and HIV-1MDR/B) in PBMCs and HIV-1ATVR5μM in MT-4 cells, with negligible cytotoxicity.

AB-506 is a small-molecule inhibitor targeting HBV core protein, inhibits viral replication in vitro (IC50=77 nM).AB-506 binds to HBV core protein, accelerates capsid assembly and inhibits HBV pgRNA encapsidation.AB-506 blocks cccDNA establishment in HBV-infected HepG2-hNTCP-C4 cells and primary human hepatocytes, leading to inhibition of viral RNA, HBsAg, and HBeAg production (EC50=0.64-1.52 uM).AB-506 demonstrated activity across HBV genotypes A-H and maintains antiviral activity against nucleostide analog-resistant variants in vitro.AB-506 showed an 8 to 20-fold increase in EC50 values against L30F, L37Q, and I105T substitutions.AB-506 exhibits good oral bioavailability, systemic exposure, and higher liver to plasma ratios in rodents.

AB-452 (AB452) is a potent, small molecule inhibitor of noncanonical poly(A) polymerases PAPD5 and PAPD7 (PAPD5/7), inhibits PAPD5/7 enzymatic activities, reduces HBsAg in vitro (EC50=1.4/6.8 nM).AB-452 demonstrated specific antiviral activity for HBV, was inactive against a panel of 10 different RNA and DNA viruses with EC50 values of >30 uM.AB-452 reduced HBsAg, HBeAg, and HBV DNA production with EC50 of 0.28-6.8 nM, without cytotoxicity.AB-452 interferes with multiple steps of HBV life cycle by reducing HBV RNA.AB-452 demonstrated antiviral activity in AAV-HBV-transduced mouse model.AB-452 promotes HBV RNA degradation through inhibiting PAPD5 and PAPD7 enzymatic activities and blockage of guanosine incorporation into viral RNA poly(A) tails..

A small molecule CD4-mimetic that binds gp120 and blocks CD4 binding, inhibits HIV-1 entry.

A highly potent, selective HCV NS5B polymerase inhibitor for treatment of HCV infection.

90 (CBR-490) is a potent and selective antiwolbachial activity compound (Anti-Wolbachia wMel In vitro HCI cell-based assay IC50=33 nM, IC90=283 nM).CBR490 demonstrates potent antiwolbachial activity was confirmed in L. sigmodontis, Brugia malayi, and Onchocerca ochengi in vivo preclinical models of filarial disease.CBR490 demonbstrated in vitro selectivity against Loa loa (a safety concern in endemic areas).

2S-alkyne is an irreversible and clickable inhibitor of Streptococcal pyrogenic exotoxin B (SpeB) with IC50 of 1.4 uM; 2S-alkyne showed irreversible enzyme inhibition in biochemical assays and labeled endogenous SpeB in cultured S. pyogenes supernatants. 2S-alkyne decreased S. pyogenes survival in the presence of human neutrophils and supports the role of SpeB-mediated proteolysis as a mechanism to limit complement-mediated host defense.

1-ECBC is a small molecule inhibiting C. albicans filamentation, 1-ABC targets DYRK1-family kinase Yak1, the sole DYRK-family member expressed in C. albicans.1-ECBC blocked C. albicans biofilm formation in several co-culture models and a rat catheter infection model.