foreskin

1,4-DPCA is an inhibitor of prolyl-hydroxylase with an IC50 of 2.4 µM for collagen hydroxylation in human foreskin fibroblasts and 60 μM for factor inhibiting HIF (FIH).

T0901317 is a potent and selective agonist for both LXR and FXR, with EC50 of ~50 nM and 5 μM, respectively; it inhibits nuclear factor κB (NF κB).

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).

U-51605, a stable analog of the endoperoxide prostaglandin H2 (PGH2), functions as an inhibitor with greater selectivity towards prostacyclin (PGI) synthase over thromboxane (TX) synthase. It also acts as a partial agonist at TP receptors. Studies show that at a concentration of 2.8 µM, U-51605 effectively inhibits PGI synthase in human foreskin fibroblasts, while a concentration of 5.6 µM is required to inhibit human platelet TX synthase. Furthermore, U-51605, at up to 1 µM, decreases the release of prostacyclin in SHR aorta triggered by the calcium ionophore A-23187 without impacting TXA2 production, and notably enhances the release of PGE2 and PGF2α.

Burnettramic acid A is a fungal metabolite originally isolated fromA. burnettiithat has diverse biological activities.1It is active againstB. subtilis,S. aureus,C. albicans, andS. cerevisiae(IC50s = 2.3, 5.9, 0.5, and 0.2 μg/ml, respectively). Burnettramic acid A is cytotoxic to NS-1 murine myeloma cells but not neonatal foreskin fibroblasts (IC50s = 13.8 and >100 μg/ml, respectively). 1.Li, H., Gilchrist, C.L.M., Lacey, H.J., et al.Discovery and heterologous biosynthesis of the burnettramic acids: Rare PKS-NRPS-derived bolaamphiphilic pyrrolizidinediones from an Australian fungus, Aspergillus burnettiiOrg. Lett.21(5)1287-1291(2019)

L-K6L9, a cytolytic peptide comprised of L-isomer leucine and lysine, demonstrates cytotoxicity against both androgen-independent (LNCaP-CL1) and androgen-dependent (22Rv1 and LNCaP) human prostate cancer cells, with LC50 values of 4, 4, and 6 µM, respectively. It also affects non-cancerous cells, including NIH3T3 mouse fibroblasts and OL human foreskin fibroblasts, with LC50s of 7 and 5 µM, respectively. Furthermore, at a concentration of 100 µM, L-K6L9 induces hemolysis in isolated human erythrocytes.

S-Acetyl-L-glutathione is a derivative of glutathione .1 It increases intracellular GSH levels in primary fibroblasts derived from patients with glutathione synthetase deficiency when used at a concentration of 50 μM. S-Acetyl-L-glutathione (5 mM) induces apoptosis in Daudi, Raji, and Jurkat lymphoma cells.2 It inhibits the replication of herpes simplex virus 1 (HSV-1) in human foreskin fibroblasts when used at concentrations of 5 and 10 mM.3 S-Acetyl-L-glutathione (6.25 μg/g per day) increases survival in a mouse model of HSV-1 infection.

Burnettramic acid A aglycone is a fungal metabolite and an aglycone form of burnettramic acid A, originally isolated from [A. burnettii], that exhibits anticancer activity. It is cytotoxic to NS-1 murine myeloma cells (IC50 = 8.4 μg ml) but not to neonatal foreskin fibroblasts (IC50 > 100 μg ml).

D-K6L9 exhibits antimicrobial and antibiofilm properties effective against Pseudomonas aeruginosa isolated from patients with cystic fibrosis. The compound demonstrates stability and resistance to degradation by proteases found in cystic fibrosis sputum and does not promote bacterial resistance [1].

L-K6L9 exhibits antimicrobial and antibiofilm properties effective against P. aeruginosa associated with cystic fibrosis, demonstrating both stability and resistance to degradation by sputum proteases from cystic fibrosis patients, without inducing bacterial resistance [1].