tp 10

TP-10 是 PDE10A 对其他 PDE 的特异性抑制剂，IC50 为 0.8 nM。

The prostaglandin E receptor 4 (EP4) is one of four G protein-coupled receptors that mediate the actions of prostaglandin E2 . Binding of PGE2 to the EP4 receptor causes an increase in intracellular cyclic AMP, which plays important roles in bone formation and resorption, cancer, and atherosclerosis. KMN-80 is a substituted γ-lactam (pyrrolidinone) derivative of PGE1 that acts as a selective and potent agonist of EP4 with an IC50 value of 3 nM (IC50 = 1.4 μM for EP3 and > 10 μM for all other prostanoid receptors). In functional assays it has been shown to stimulate secreted alkaline phosphatase gene reporter activity in EP4-transfected HEK293 cells with an EC50 value of 0.19 nM, demonstrating >5,000 and 50,000-fold selectivity against EP2 and TP, respectively. KMN-80 can induce the differentiation of bone marrow stem cells from both young and aged rats into osteoblasts in vitro (EC50s = 20 and 153 nM, respectively) and exhibits favorable tolerability up to at least 10 μM, whereas the EP4 agonist L-902,688 is highly cytotoxic at similar concentrations in these cells. KMN-80 has been used to repair calvarial defects in an in vivo rat craniomaxillofacial reconstruction model (rate of reduction in defect size equivalent to BMP-2 treated rats) and to promote bone formation in a rat incisor tooth socket model.

NHC-triphosphate triammonium is an active phosphorylated intracellular metabolite of β-d-N4-Hydroxycytidine (NHC) as a triphosphate form[1]. NHC-triphosphate triammonium is a weak alternative substrate for the viral polymerase and can be incorporated into HCV replicon RNA[1][2]. In an intracellular metabolism assay, HCV replicon cells are treated with 10 μM 3H-labeled NHC, and intracellular nucleotide levels are determined after 1, 2 and 8 hours incubations. NHC is rapidly convered into the mono-, di-, and triphosphate forms, and NHC-TP reaches up to 71.12 pM after 8 hours[1].NHC-triphosphate triammonium (NHC-TP) (5-40 μM) absence leads to full-length polymerization products, it can be a weak alternative substrate. In addition, incorporation of NHC-TP instead of CTP increases the molecular weight of the polymerization product by 16 (one extra oxygen) for each event and an obvious electrophoretic shift is observed in cell-free HCV NS5B polymerization reactions[1].Huh-7 cells are incubated with (10-50 μM; 4 h) NHC or a McGuigan phosphoramidate prodrug of NHC. Intracellular levels of the parental compounds and phosphorylated metabolites are measured using LC-MS MS. Small amounts of NHC-monophosphate (MP) and NHC-diphosphate (DP) can be observed, while NHC-triphosphate triammonium remains the most abundant metabolite[2].NHC-triphosphate triammonium (NHC-TP) metabolite may directly target the viral polymerase and behave as a nonobligate chain terminator. It plays a prominent role in inhibiting early negative-strand RNA synthesis, either through chain termination or mutagenesis, which may in turn interfere with correct replicase complex formation. [1]. Stuyver LJ,et al. Ribonucleoside analogue that blocks replication of bovine viral diarrhea and hepatitis C viruses in culture.Antimicrob Agents Chemother. 2003 Jan;47(1):244-54. [2]. Maryam Ehteshami, et al. Characterization of β-d- N4-Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus.

NU1085 is a potent poly(ADP-ribose) polymerase (PARP) inhibitors have been developed that potentiate the cytotoxicity of ionizing radiation and anticancer drugs. The biological effects of NU1085 [Ki = 6 nM], in combination with temozolomide (TM) or topotecan (TP) have been studied in 12 human tumor cell lines (lung, colon, ovary, and breast cancer). Cells were treated with increasing concentrations of TM or TP + - NU1085 (10 microM) for 72 h.

TP-1454是一种针对PKM2的激活剂，其生化测定的AC50为10 Nm。它可通过作用于T调节细胞来调控肿瘤的免疫反应。

TP-064 是选择性蛋白精氨酸甲基转移酶 4 抑制剂 ，IC50小于10 nM，具有抗癌活性。它抑制 BAF155 和 MED12 的二甲基化，IC50为 340 和 43 nM。它对于 PRMT6 的 IC50为 1.3 μM。