replication protein a

TDRL-551 is a novel and potent replication protein A (RPA) inhibitor (IC50=18 µM) with potential anticancer activity.TDRL-551 inhibits RPA-DNA interaction and enhances the efficacy of platinum-based chemotherapy for lung and ovarian cancer.

Daunorubicin hydrochloride (Rubidomycin hydrochloride), an anthracycline aminoglycoside antineoplastic, inhibits DNA replication and repair and RNA and protein synthesis.

2'-O-Methylcytidine is a nucleoside derivative and an inhibitor of hepatitis C virus (HCV) non-structural protein 5B (NS5B; IC50= 3.8 μM).1It inhibits HCV replication in a replicon assay (IC50= 21.2 μM). 1.Migliaccio, G., Tomassini, J.E., Carroll, S.S., et al.Characterization of resistance to non-obligate chain-terminating ribonucleoside analogs that inhibit hepatitis C virus replication in vitroJ. Bio. Chem.278(49)49164-49170(2003)

N-Acetyl-L-cysteine ethyl ester (NACET) is a derivative of the amino acid L-cysteine. NACET has been shown to exhibit diverse biochemical and physiological effects, including inhibition of protein synthesis, inhibition of DNA replication, and induction of apoptosis. Additionally, it has demonstrated anti-inflammatory, antioxidant, and anti-cancer activity.

Tubercidin (Sparsomycin A), an adenosine analogue, is a nucleoside antibiotic. It is incorporated into DNA and inhibits polymerases, thereby inhibiting DNA replication and RNA and protein synthesis. This agent also exhibits antifungal and antiviral activities.

PF-3450074 (PF-74) acts at an early stage of HIV-1 infection inhibits viral replication by directly competing with the binding of CPSF6 (nuclear host factors cleavage and polyadenylation specific factor 6) and NUP153 (nucleoporin 153), and blocks the uncoating, assembly, and the reverse transcription steps of the viral life cycle. PF-3450074 is a specifical inhibitor of HIV-1 capsid protein (CA) and shows a broad-spectrum inhibition of HIV isolates with submicromolar potency (EC50=8-640 nM).

Beclabuvir is an allosteric inhibitor that binds to thumb site 1 of the HCV NS5B RNA-dependent RNA polymerase, inhibiting recombinant NS5B proteins from HCV genotypes 1, 3, 4, and 5 (IC50 < 28 nM).

BRD5631 is an autophagy enhancer that operates through an mTOR-independent pathway. It influences several cellular disease phenotypes associated with autophagy, such as protein aggregation, cell survival, bacterial replication, and inflammatory cytokine production. BRD5631 can serve as a valuable tool for studying the role of autophagy in cellular homeostasis and disease. [1].

Cdc7-IN-5 is a potent inhibitor of Cdc7 kinase. Cdc7, a serine-threonine protein kinase enzyme, is essential for the initiation of DNA replication in the cell cycle.

IR415 selectively interacts with Hepatitis B virus X protein (HBx, Kd = 2 nM) and blocks HBV-mediated RNAi suppression, reverses the inhibitory effect of HBx protein on the activity of the dicer endoribonuclease. IR415 is a potent anti-HBV agent and inhibits HBV replication by blocking the HBx activity.

RN-18 antagonizes Vif function and inhibits HIV-1 replication only in the presence of A3G. RN-18 increases cellular A3G levels in a Vif-dependent manner and increases A3G incorporation into virions without inhibiting general proteasome-mediated protein degradation. RN-18 enhances Vif degradation only in the presence of A3G, reduces viral infectivity by increasing A3G incorporation into virions and enhances cytidine deamination of the viral genome.

Pentamethylmelamine, as a primary metabolite of hexamethylmelamine, exhibits antitumor activity. This compound alkylates DNA and other macromolecules, leading to the formation of DNA intra-strand and DNA-protein cross-links, thereby inhibiting DNA replication.

TDI-015051 is an orally active inhibitor of SARS-CoV-2 non-structural protein 14 (SARS-CoV-2 NSP14) with an IC50 of ≤0.15 nM. It effectively inhibits SARS-CoV-2 NSP14 in Huh-7.5 cells (EC50=11.4 nM) and A549 cells expressing ACE2-TMPRSS2 (EC50=64.7 nM). Additionally, TDI-015051 suppresses other coronaviruses such as α-hCoV-NL63, α-hCoV-229E, and β-hCoV-MERS with IC50 values of 1.7, 2.6, and 3.6 nM, respectively. This compound inhibits viral RNA methylation and replication by binding to a stable SAH-cap pocket and demonstrates anti-infection activity in mouse models.

RJS308 is a PROTAC degrader of cyclosporin A (cyclosporin A) with a DC50 of 284 nM. It exhibits antiviral activity by inhibiting the replication of HIV-1 and HCV. (Pink: ligand for target protein CypA ligand-2; Black: linker; Blue: ligand for E3 ligase VHL (S,R,S)-AHPC-Me)

KR019 is a potent hepatitis B virus (HBV) capsid assembly modulator that demonstrates significant antiviral activity in HBV cells. It binds to the hydrophobic pocket at the core protein dimer-dimer interface, redirecting capsid assembly into genome-free capsids, thereby inhibiting viral replication.

3′-Deoxy CTP trisodium is the sodium salt form of 3′-Deoxy CTP. This compound is a nucleotide analog known as a chain terminator. By lacking a 3′-hydroxyl group, it causes chain termination and inhibits the RNA synthesis activity of the HCV non-structural protein (NS5B) polymerase, thereby blocking viral replication. 3′-Deoxy CTP trisodium is utilized in the study of chain termination mechanisms of HCV polymerase and the development of antiviral drugs.

3′-Deoxy CTP is a nucleotide analog that functions as a potent chain terminator. By lacking a 3′-hydroxyl group, 3′-Deoxy CTP induces chain termination, thereby inhibiting the RNA synthesis activity of HCV non-structural protein (NS5B) polymerase and halting viral replication. This compound is useful for studying the chain termination mechanism of HCV polymerases and for developing antiviral drugs.

SM875 is a degrader specifically targeting the cellular prion protein (PrP) with an IC50 of 7.87 μM. By binding to the folding intermediates of PrP, SM875 facilitates their degradation via the autophagy-lysosome pathway. It acts exclusively on nascent, immature PrP molecules and does not affect mature PrP synthesized beforehand. SM875 has the potential to inhibit prion replication, making it a promising compound for research in neurodegenerative diseases, particularly prion diseases.

YZ51, a novel potent inhibitor of ribonucleotide reductase (RR), inhibits hepatitis B virus replication by targeting ribonucleotide reductase M2 protein.

Disoxaril (BRN 3626820, WIN 51711) is an anti-picornavirus agent that inhibits enterovirus replication by binding to a hydrophobic bag within the VP1 coat protein, thereby stabilizing virions and preventing their uncoating. When used in combination with A

Paritaprevir free base(ABT-450) is an orally bioavailable, synthetic acylsulfonamide inhibitor of the hepatitis C virus (HCV) protease complex comprised of non-structural protein 3 and 4A (NS3 NS4A), with potential activity against HCV genotype 1. Upon administration, paritaprevir reversibly binds to the active center and binding site of the HCV NS3 NS4A protease and prevents NS3 NS4A protease-mediated polyprotein maturation. This disrupts both the processing of viral proteins and the formation of the viral replication complex, which inhibits viral replication in HCV genotype 1-infected host cells. NS3, a serine protease, is essential for the proteolytic cleavage of multiple sites within the HCV polyprotein and plays a key role during HCV ribonucleic acid (RNA) replication. NS4A is an activating factor for NS3. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family, and infection is associated with the development of hepatocellular carcinoma (HCC).

Dasabuvir (ABT-333) is a non-nucleoside inhibitor of the hepatitis C virus (HCV) non-structural protein 5B (NS5B), an RNA-dependent RNA polymerase. Upon administration and intracellular uptake, dasabuvir binds HCV NS5B polymerase, blocking viral RNA synthesis and replication. The HCV NS5B protein is essential for the replication of the HCV RNA genome.

FSL-1 TFA, a toll-like receptor 2/6 (TLR2/6) agonist derived from bacteria, bolsters resistance against experimental HSV-2 infection[1] and stimulates MMP-9 production via the TLR2 and NF-κB/AP-1 signaling pathways in monocytic THP-1 cells[2].

O-11 is an analog of the fully saturated, 14-carbon fatty acid myristic acid, in which the methylene group at position 11 is replaced with oxygen. It is highly effective and selective at killingTrypanosoma brucei, the protozoan parasite responsible for African sleeping sickness, exhibiting an LD50of less than 1 μM in a cell culture assay.1,2The toxic effects of O-11 appear to be caused by its ability to inhibit the incorporation of a single myristate into the GPI anchor of the variant surface glycoprotein (VSG), a protein critical for evading the host immune response.1O-11 exhibits essentially no anti-fungal activity when assayed usingC. neoformans, but does have a minor inhibitory effect on HIV-1 replication in T-lymphocytes.3 1.Doering, T.L., Raper, J., Buxbaum, L.U., et al.An analog of myristic acid with selective toxicity for African trypanosomesScience2521851-1854(1991) 2.Doering, T.L., Lu, T., Werbovetz, K.A., et al.Toxicity of myristic acid analogs toward African trypanosomesProceedings of the National Academy of Sciences of the United States of America919735-9739(1994) 3.Langner, C.A., Lodge, J.K., Travis, S.J., et al.4-Oxatetradecanoic acid is fungicidal for Cryptococcus neoformans and inhibits replication of human immunodeficiency virus IThe Journal of Biological Chemisty267(24)17159-17169(1992)