sk-1-in-1

SK1-IN-1是一种可口服且具有高效性的鞘氨醇激酶1 (SPHK1) 抑制剂（IC50：58 nM），具有潜在的抗癌活性，可用于研究癌症和神经退行性疾病。

TASK-1-IN-1 是一种有效的选择性的 TASK-1 (Potassium Channel) 抑制剂（IC50 ： 148 nM）。TASK-1-IN-1 对 TASK-3 通道 的IC50 为 1750 nM，抑制作用有所降低。TASK-1-IN-1 具有抗癌作用。

ASK1-IN-1 是一种凋亡信号调节激酶 1（SK1） 抑制剂，具有良好的效价 (细胞IC50=138 nM; BiochemicalIC50=21 nM)。ASK1-IN-1具有中枢神经系统渗透性。

SZU-B6, 作为一种PROTAC降解剂，能够有效降解目标蛋白SIRT6。在SK-HEP-1与Huh-7细胞系中，SIRT6的DC50值分别达到45 nM及154 nM。SZU-B6对SK-HEP-1细胞的增殖具有抑制作用，其IC50为1.51 μM，并能有效抑制SK-HEP-1与Huh-7细胞的集落形成，诱导SK-HEP-1细胞的凋亡(apoptosis)，同时在G2/M期阻滞细胞周期。此外，SZU-B6在小鼠模型中显示出显著的抗肿瘤活性。(Pink: 靶蛋白配体; Black: 连接子; Blue: E3连接酶配体)

TRBP-IN-1 (Compound 13j) 是一种口服有效的 TAR RNA 结合蛋白 2 (TRBP) 抑制剂，IC50 为 12.72 μM。TRBP-IN-1 展现出显著的抗肝细胞癌 (HCC) 活性，有效抑制 HCC 细胞（HCCLM3 细胞 IC50 为 18.96 μM；SK-Hep-1 细胞 IC50 为 16.45 μM）的增殖与转移。通过靶向 TRBP，TRBP-IN-1 调控 miRNA 生物合成并抑制致癌 miRNA 的表达，诱导 HCC 细胞的凋亡和焦亡。该化合物可用于针对 HCC 的靶向治疗研究。

MASTL/Aurora A-IN-1 (Compound MA4) 是一种针对 MASTL 和 Aurora A 激酶的双重抑制剂，其 IC50 分别为 0.56 μM 和 0.16 μM。此化合物在 NCI-60 癌细胞系中展现出广泛的抗癌活性，尤其对 SR（白血病）、K-562（白血病）、MDA-MB-435（黑色素瘤）、MOLT-4（白血病）和 SK-MEL-2（黑色素瘤）细胞系，GI50 分别为 0.023、0.032、0.037、0.044 和 0.051 μM。通过抑制 Aurora A 和 MASTL 激酶，MASTL/Aurora A-IN-1 能诱导细胞周期停滞在 G2/M 期，从而抑制癌细胞的增殖。此化合物可应用于癌症研究，特别是针对有丝分裂异常的肿瘤。

QC-182 是一种高效的 p300/CBPPROTAC 降解剂，能够在 SK-HEP-1 细胞中降低 p300 蛋白 (DC50= 93nM)。此外，QC-182 显著抑制 SK-HEP-1 和 JHH7 细胞系的生长，其 IC50 分别为 0.733 和 0.477 μM。QC-182 可用于肝细胞癌 (HCC) 的研究。

SK-216（化合物 SK-216） 是一种特异性 PAI-1 抑制剂，可减少肿瘤血管生成，并抑制体外 VEGF 诱导的人脐静脉内皮细胞迁移和管形成。该化合物还能减轻小鼠中博莱霉素诱导的肺纤维化程度。

Ganglioside GD3 is synthesized by the addition of two sialic acid residues to lactosylceramide and can serve as a precursor to the formation of more complex gangliosides by the action of glycosyl- and sialyltransferases. It induces apoptosis in HuT-78 cutaneous T cell lymphoma cells in a concentration-dependent manner and disrupts the mitochondrial membrane potential when used at a concentration of 200 μM. Expression of ganglioside GD3 in GD3-negative SK-MEL-28-N1 malignant melanoma cells increases both cell proliferation and invasion in vitro. Ganglioside GD3-deficient adult mice exhibit progressive loss of the neural stem cell (NSC) pool and impaired neurogenesis. Ganglioside GD3 mixture contains ganglioside GD3 molecular species with C18:1 and C20:1 sphingoid backbones.

2-deoxy-D-Glucose-13C6is intended for use as an internal standard for the quantification of 2-deoxy-D-glucose by GC- or LC-MS. 2-deoxy-D-Glucose is a glucose antimetabolite and an inhibitor of glycolysis.1,2It inhibits hexokinase, the enzyme that converts glucose to glucose-6-phosphate, as well as phosphoglucose isomerase, the enzyme that converts glucose-6-phosphate to fructose-6-phosphate.32-deoxy-D-Glucose (16 mM) induces apoptosis in SK-BR-3 cells, as well as inhibits the growth of 143B osteosarcoma cells cultured under hypoxic conditions when used at a concentration of 2 mg/ml.4,5In vivo, 2-deoxy-D-glucose (500 mg/kg) reduces tumor growth in 143B osteosarcoma and MV522 non-small cell lung cancer mouse xenograft models when used alone or in combination with doxorubicin or paclitaxel .6 1.Kang, H.T., and Hwang, E.S.2-Deoxyglucose: An anticancer and antiviral therapeutic, but not any more a low glucose mimeticLife Sci.78(12)1392-1399(2006) 2.Aft, R.L., Zhang, F.W., and Gius, D.Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: Mechanism of cell deathBr. J. Cancer87(7)805-812(2002) 3.Ralser, M., Wamelink, M.M., Struys, E.A., et al.A catabolic block does not sufficiently explain how 2-deoxy-D-glucose inhibits cell growthProc. Natl. Acad. Sci. USA105(46)17807-17811(2008) 4.Liu, H., Savaraj, N., Priebe, W., et al.Hypoxia increases tumor cell sensitivity to glycolytic inhibitors: A strategy for solid tumor therapy (Model C)Biochem. Pharmacol.64(12)1745-1751(2002) 5.Zhang, X.D., Deslandes, E., Villedieu, M., et al.Effect of 2-deoxy-D-glucose on various malignant cell lines in vitroAnticancer Res.26(5A)3561-3566(2006) 6.Maschek, G., Savaraj, N., Priebe, W., et al.2-deoxy-D-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivoCancer Res.64(1)31-34(2004)

Pituitary adenylate cyclase-activating peptide (PACAP) (6-27) is a PACAP receptor antagonist with IC50 values of 1,500, 600, and 300 nM, respectively, for rat PAC1, rat VPAC1, and human VPAC2 recombinant receptors expressed in CHO cells. It binds to PACAP receptors on SH-SY5Y and SK-N-MC human neuroblastoma and T47D human breast cancer cells (IC50s = 24.5, 106, and 105 nM, respectively) and inhibits cAMP accumulation induced by PACAP (1-38) (Kis = 457, 102, and 283 nM, respectively, in SH-SY5Y, SK-N-MC, and T47D cells). In vivo, in newborn pigs, PACAP (6-27) (10 μM) inhibits vasodilation of pial arterioles induced by PACAP (1-27) and PACAP (1-38) . It also inhibits PACAP (1-27)-stimulated increases in plasma insulin and glucagon levels and pancreatic venous blood flow in dogs when administered locally to the pancreas at a dose of 500 μg.

ARN14988 is a potent inhibitor of acid ceramidase (IC50 = 12.8 nM for the human enzyme). It inhibits acid ceramidase activity and increases levels of C16 dihydro ceramide and C16 ceramide in A375, G361, M14, MeWo, MNT-1, and SK-MEL-28 melanoma cells. ARN14988 also reduces growth of A375 and G361 melanoma cells (EC50s = 41.8 and 67.7 μM, respectively).

Nocardamine is a ferrioxamine siderophore that has been found inStreptomycesand has diverse biological activities.1,2,3,4It chelates iron in a chrome azurol S assay (IC50= 9.9 μM).1Nocardamine inhibitsM. smegmatisandM. bovisbiofilm formation (MIC = 10 μM for both), an effect that can be reversed by iron.2It is cytotoxic to T47D, SK-MEL-5, SK-MEL-28, and RPMI-7951 cancer cells (IC50s = 6, 18, 12, and 14 μM, respectively).3Nocardamine also induces morphological changes in BM-N4 insect cells.4 1.Lopez, J.A.V., Nogawa, T., Futamura, Y., et al.Nocardamin glucuronide, a new member of the ferrioxamine siderophores isolated from the ascamycin-producing strain Streptomyces sp. 80H647J. Antibiot. (Tokyo)72(12)991-995(2019) 2.Ishida, S., Arai, M., Niikawa, H., et al.Inhibitory effect of cyclic trihydroxamate siderophore, desferrioxamine E, on the biofilm formation of Mycobacterium speciesBiol. Pharm. Bull.34(6)917-920(2011) 3.Kalinovskaya, N.I., Romaneko, L.A., Irisawa, T., et al.Marine isolate Citricoccus sp. KMM 3890 as a source of a cyclic siderophore nocardamine with antitumor activityMicrobiol. Res.166(8)654-661(2011) 4.Matsubara, K., Sakuda, S., Tanaka, M., et al.Morphological changes in insect BM-N4 cells induced by nocardamineBiosci. Biotechnol. Biochem.62(10)2049-2051(1998)

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).

Stephacidin B is a fungal metabolite that has been found inA. ochraceus.1Dimeric stephacidin B is rapidly converted to a monomer, avrainvillamide ,in vitro.2Stephacidin B is cytotoxic to a variety of cancer cells, including testosterone-independent PC3 and -sensitive LNCaP prostate cancer cells (IC50s = 0.37 and 0.06 μM, respectively) and estradiol-independent SK-BR-3 and -sensitive MCF-7 breast cancer cells (IC50s = 0.32 and 0.27 μM, respectively).1It induces apoptosis in HepG2 and Huh7 hepatocellular carcinoma cells when used at a concentration of 4 μM.3 1.Qian-Cutrone, J., Huang, S., Shu, Y.-Z., et al.Stephacidin A and B: Two structurally novel, selective inhibitors of the testosterone-dependent prostate LNCaP cellsJ. Am. Chem. Soc.124(49)14556-14557(2002) 2.Wulff, J.E., Herzon, S.B., Siegrist, R., et al.Evidence for the rapid conversion of stephacidin B into the electrophilic monomer avrainvillamide in cell cultureJ. Am. Chem. Soc.129(16)4898-4899(2007) 3.Hu, L., Zhang, T., Liu, D., et al.Notoamide-type alkaloid induced apoptosis and autophagy via a P38/JNK signaling pathway in hepatocellular carcinoma cellsRSC Adv.9(34)19855-19868(2019)

C4 Ceramide is a bioactive sphingolipid and cell-permeable analog of naturally occurring ceramides. [1] [2] [3] It inhibits IL-4 production by 16% in EL4 T cells stimulated with phorbol 12-myristate 13-acetate when used at a concentration of 10 μM. [1] C4 Ceramide is cytotoxic to SK-BR-3 and MCF-7/Adr breast cancer cells (IC50s = 15.9 and 19.9 μM, respectively). [2] C4 Ceramide also increases maturation and stability of cystic fibrosis transmembrane conductance regulator (CFTR) proteins bearing the F508 deletion (F508del) mutation, enhances cAMP-activated chloride secretion, and suppresses secretion of IL-8 in primary epithelial cells isolated from patients with cystic fibrosis.[3]

Notoginsenoside Fa 是一种原人参二醇型皂苷，从P. notoginseng 提取出来得到，有激活和恢复退化脑功能的潜能。

NS309 是选择性钙依赖性钾离子通道 SK/IK 的激活剂，在 BK 通道上没有激活作用。

BRD9500 是一种具有口服活性的磷酸二酯酶 3 (PDE3) 抑制剂，对PDE3A 和PDE3B 的IC50分别为 10 和 27 nM。BRD9500 在黑色素瘤细胞系 SK-MEL-3 癌症异种移植模型中具有活性。

ACA-28是一种ERK MAPK信号调节剂，能够过度激活ERK从而诱导黑黑色素瘤细胞凋亡，对黑色素瘤细胞 (SK-MEL-28) 和正常黑色素细胞 (NHEM)的IC50值分别为5.3和10.1μM。

Ginsenoside Rg5 是红参的主要成分，可阻断IGF-1与其受体的结合，IC50约为90 nM。它还通过抑制NF-κB p65的 DNA 结合活性来抑制COX-2的 mRNA 表达。它可促进血管生成和改善高血压，具有抗炎和治疗阿尔茨海默病的潜力。

VPC03090 is a Sphingosine-1-Phosphate Receptor Inhibitor. VPC03090 is an analog of FTY-720, acts as antagonist for S1PR1 and S1PR3. VPC03090-P, converted from VPC03090 through the phosphorylation by SK-2, causes a reduction in tumor growth in mice with mammary cancer, and its oral bioavailability is determined to be 30 hours.

Antitumor agent-61 (Compound 9b)，Irinotecan (Ir)的衍生物，展现出对多种肿瘤细胞（包括SK-OV-3、SK-OV-3/CDDP、U2OS、MCF-7、A549与MG-63）具有显著的抑制效果，其IC50值分别为0.92、1.39、1.75、2.20、3.05和3.23 μM。该化合物主要通过线粒体途径引发SK-OV-3细胞的凋亡。

UBA5-IN-1 (compound 8.5) 是 UBA5的选择性抑制剂，IC50值为 4.0 μM。UBA5-IN-1 抑制高表达 UBA5 的 Sk-Luci6 癌细胞的增殖。