embryonic fibroblasts

RBC10 抑制 Ral 与其效应物 RALBP1 的结合，以及抑制 Ral 介导的鼠胚胎成纤维细胞的细胞扩散和人类癌细胞系的非贴壁依赖性生长。

OAC2 是一种 Oct4 激活剂，通过 Oct4 基因启动子激活表达， 通过提高胚胎成纤维细胞诱导多能干细胞的产生速率来提高重编程效率，是 OAC1 的类似物。

C6 urea ceramide is an inhibitor of neutral ceramidase.1 It increases total ceramide levels in wild-type mouse embryonic fibroblasts (MEFs) and in HT-29 colon cancer cells but not in MEFs lacking neutral ceramidase. It inhibits proliferation of, and induces apoptosis and autophagy in HT-29, but not non-cancerous RIE-1, cells when used at concentrations of 5 and 10 μM. C6 urea ceramide decreases total β-catenin, increases phosphorylated β-catenin, and induces colocalization of β-catenin with the 20S proteasome in HT-29 and HCT116, but not RIE-1, cells. It reduces tumor growth and increases C16, C18, C20, and C24 ceramide levels in tumor tissue in an HT-29 mouse xenograft model when administered at doses of 1.25, 2.5, and 5 mg/kg for five days. |1. García-Barros, M., Coant, N., Kawamori, T., et al. Role of neutral ceramidase in colon cancer. FASEB J. 30(12), 4159-4171 (2016).

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).

1-Stearoyl-2-15(S)-HpETE-sn-glycero-3-PE is a phospholipid that contains stearic acid at the sn-1 position and 15(S)-HpETE at the sn-2 position. It is produced via oxidation of 1-stearoyl-2-arachidonoyl-sn-glycero-3-PE by 15-lipoxygenase (15-LO). 1-Stearoyl-2-15(S)-HpETE-sn-glycero-3-PE (0.6 and 0.9 μM) increases ferroptotic cell death in wild-type and Acsl4 knockout Pfa1 mouse embryonic fibroblasts (MEFs) treated with the GPX4 inhibitor RSL3.

C22 dihydro 1-Deoxyceramide (m18:0/22:0) is a very long-chain atypical ceramide containing a 1-deoxysphinganine backbone. 1-Deoxysphingolipids are formed when serine palmitoyltransferase condenses palmitoyl-CoA with alanine instead of serine during sphingolipid synthesis.1,2 C22 dihydro 1-Deoxyceramide (m18:0/22:0) has been found in mouse embryonic fibroblasts (MEFs) following application of 1-deoxysphinganine alkyne or 1-deoxysphinganine-d3.3 It has also been found as the most prevalent dihydro deoxyceramide species in mouse brain, spinal cord, and sciatic nerve at one, three, and six months of age.4 |1. Steiner, R., Saied, E.M., Othman, A., et al. Elucidating the chemical structure of native 1-deoxysphingosine. J. Lipid Res. 57(7), 1194-1203 (2016).|2. Alecu, I., Othman, A., Penno, A., et al. Cytotoxic 1-deoxysphingolipids are metabolized by a cytochrome P450-dependent pathway. J. Lipid Res. 58(1), 60-71 (2017).|3. Alecu, I., Tedeschi, A., Behler, N., et al. Localization of 1-deoxysphingolipids to mitochondria induces mitochondrial dysfunction. J. Lipid. Res. 58(1), 42-59 (2017).|4. Schwartz, N.U., Mileva, I., Gurevich, M., et al. Quantifying 1-deoxydihydroceramides and 1-deoxyceramides in mouse nervous system tissue. Prostaglandins Other Lipid Mediat. 141, 40-48 (2019).

C24 dihydro 1-Deoxyceramide (m18:0/24:0) is a very long-chain atypical ceramide containing a 1-deoxysphinganine backbone. 1-Deoxysphingolipids are formed when serine palmitoyltransferase condenses palmitoyl-CoA with alanine instead of serine during sphingolipid synthesis.1,2 C24 dihydro 1-Deoxyceramide (m18:0/24:0) has been found in mouse embryonic fibroblasts (MEFs) following application of 1-deoxysphinganine alkyne or 1-deoxysphinganine-d3.3 It has also been found in mouse brain, spinal cord, and sciatic nerve at one, three, and six months of age.4 |1. Steiner, R., Saied, E.M., Othman, A., et al. Elucidating the chemical structure of native 1-deoxysphingosine. J. Lipid Res. 57(7), 1194-1203 (2016).|2. Alecu, I., Othman, A., Penno, A., et al. Cytotoxic 1-deoxysphingolipids are metabolized by a cytochrome P450-dependent pathway. J. Lipid Res. 58(1), 60-71 (2017).|3. Alecu, I., Tedeschi, A., Behler, N., et al. Localization of 1-deoxysphingolipids to mitochondria induces mitochondrial dysfunction. J. Lipid. Res. 58(1), 42-59 (2017).|4. Schwartz, N.U., Mileva, I., Gurevich, M., et al. Quantifying 1-deoxydihydroceramides and 1-deoxyceramides in mouse nervous system tissue. Prostaglandins Other Lipid Mediat. 141, 40-48 (2019).

UC-857993 是一种选择性SOS1-Ras 抑制剂 (Kd=14.7 μM, His6-SOS1cat)，抑制其催化活性。UC-857993 还能抑制ERK 和Ras 激活，抑制小鼠胚胎成纤维细胞 (MEF) 的生长。

Kras4B G12D-IN-1为Kras4B G12D的抑制剂，表现出抗癌活性。在降低Kras4B G12D表达的小鼠胚胎成纤维细胞(MEF)中减少Kras蛋白水平。