mrc-5

2-Fluoroadenine (NSC-27364) has toxicity in nonproliferating and proliferating tumor cells. 2-Fluoroadenine can be used for anticancer studies.

Mirodenafil is a PDE-5 inhibitor developed for the treatment of erectile dysfunction.

HDAC-IN-83 (compound 9D) is an inhibitor of histone deacetylase (HDAC), demonstrating an IC50 of 0.01 μM for HDAC1 and 0.44 μM for HDAC6. It exhibits anticancer and antiproliferative activities and promotes caspase-3 7 activation. The compound inhibits Cal27, HepG2, and MRC-5 cells with IC50 values of 0.693 μM, 0.427 μM, and 3.19 μM, respectively.

HR-568 displays broad-spectrum anti-enterovirus activity. It inhibits enterovirus strains EV-A71, E30, and CVA24 in MRC-5 cells, with EC50 values of 1.53 μM, 0.4 μM, and 1.22 μM, respectively. HR-568 targets the hydrophobic pocket on enterovirus capsid proteins, thereby hindering viral replication.

Omaciclovir (ABT-091) is a selective herpesvirus herpesvirus replication inhibitor and a nucleoside analog with antiviral activity for the study of herpesvirus infections.

Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013). Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3 References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013).

MtTMPK-IN-1 (compound 3) is a highly effective inhibitor of Mycobacterium tuberculosis thymidylate kinase (Mt TMPK), with an IC50 value of 2.5 μM. It shows moderate to weak activity against Mtb H37Rv and low cytotoxicity in human fibroblast cells MRC-5, making it a valuable tool for tuberculosis research [1].

MtTMPK-IN-2 (compound 15), a potent inhibitor of Mycobacterium tuberculosis thymidylate kinase (Mt TMPK), demonstrates an IC50 value of 1.1 μM. This compound effectively inhibits Mtb H37Rv with a minimum inhibitory concentration (MIC) of 12.5 μM and exhibits cytotoxicity in MRC-5 human fibroblast cells with an EC50 of 6.1 μM. MtTMPK-IN-2 is valuable for tuberculosis research [1].

MtTMPK-IN-3 (compound 25) is a potent inhibitor of Mycobacterium tuberculosis thymidylate kinase (MtTMPK) with an IC50 value of 0.12 μM. It also exhibits inhibitory activity against Mtb H37Rv with a MIC of 12.5 μM and shows cytotoxicity in MRC-5 human fibroblast cells (EC50 = 12.5 μM). This compound is useful for tuberculosis research [1].

ML251 is a potent novel nanomolar inhibitor of T. brucei and T. cruzi phosphofructokinase[1]. ML251 inhibits T. brucei PFK (IC50=0.37 μM) and T. cruzi PFK (IC50=0.13 μM). ML251 can be used for the research of parasite[1].

Galectin-3 galectin-8-IN-1 (Compound 53) serves as a dual inhibitor of the Galectin-3 and galectin-8 C-terminal domains, exhibiting dissociation constants (Kd) of 4.12 μM for Galectin-3 and 6.04 μM for galectin-8. It effectively impedes the migration of MRC-5 lung fibroblast cells and is utilized in cancer and tissue fibrosis research [1].

Galectin-3 galectin-8-IN-2 (Compound 57) is a dual inhibitor targeting the C-terminal domains of Galectin-3 and galectin-8, with dissociation constants (Kd) of 12.8 μM and 2.06 μM, respectively. It effectively inhibits MRC-5 lung fibroblast cell migration and serves as a potential research tool for studying cancer and tissue fibrosis [1].

NPD-2975 (compound 30) is an orally active antitrypanosomal agent effective against Human African Trypanosomiasis (HAT), demonstrating acceptable metabolic stability and low toxicity potential in human MRC-5 lung fibroblasts, as well as in an acute mouse model of T. b. brucei infection. It exhibits an in vitro IC50 of 70 nM against T. b. brucei and IC50 values of 0.16 μM and 0.42 μM against CYP1A2 and CYP2C19 enzymes, respectively [1].

BRC4wt, an acetylated peptide originating from the BRC4 repeat within human BRCA2 (1521-1536), acts as an inhibitor of the BRCA2 and RAD51 protein-protein interaction. When linked to the cationic cell-penetrating peptide (Arg)9, it effectively shortens DNA replication tract lengths and diminishes the frequency of homologous repair of camptothecin-induced DNA damage in vitro. Additionally, BRC4wt enhances the efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib in inducing cell death in HeLa human cervical cancer and U2OS human osteosarcoma cells, albeit it does not affect non-cancerous hTERT RPE-1, MRC-5, or MCF-10A cells.

HP661, a selective inhibitor of mitochondrial complex I (NADH dehydrogenase), impedes complex I activity by 77.6% at 1 µM, demonstrating lesser inhibition towards complex III (28.1%) and no inhibitory effects on complexes II and IV. It notably decreases the viability of human lung cancer cells—H460, NCI H441, and trametinib-resistant A549 cells (IC50s = 10.6, 29.7, and 15.1 nM, respectively)—which exhibit high levels of oxidative phosphorylation. In contrast, it shows minimal activity against NCI H358 lung cancer cells and non-cancerous HPNE and MRC-5 cells (IC50s = >10,000 nM for both), which have lower oxidative phosphorylation levels. Furthermore, in an H460 mouse xenograft model, HP661 at a dose of 30 mg/kg twice daily significantly reduces tumor volume and enhances the tumor-growth inhibitory effects of trametinib.

EV-A71-IN-2 (compound 6c) is an antiviral agent targeting Enterovirus A71, exhibiting EC50 values of 0.29 μM in EV-A71-MRC-5 cells and 1.66 μM in EV-A71-RD cells. It is utilized in research focused on Enterovirus infections.

Mirodenafil dihydrochloride is a PDE-5 inhibitor developed for the treatment of erectile dysfunction.