tp-4

ETP-46464 is an effective and specific ATR inhibitor (IC50: 25 nM).

ETP-45658 (ETP45658) is a PI 3-kinase inhibitor (IC50 values are 22, 30, 129 and 710 nM for PI 3-Kα, PI 3-Kδ, PI 3-Kβ and PI 3-Kγ respectively). Also inhibits DNA-PK and mTOR (IC50 values are 70.6 and 152 nM respectively).

TP-4748 is a biochemical.

ETP-46321 is an effective and orally bioavailable PI3Kα PI3Kδ inhibitor (Ki: 2.3 14.2 nM).

TP-472 is a selective inhibitor of BRD9 (Kd: 33 nM).

D-106669, an inhibitor of Erk2, exhibits an IC50 of 18.7 μM and effectively suppresses cell proliferation with an EC50 of 0.9 μM.

CTP499, a selective PDE inhibitor, and the deuterium-containing agent is an HDX analogue and a metabolite of hexantheobromine that slows the progression of type 2 diabetic nephropathy in patients with macroalbuminuria.

TP-422 is a negative control for TP-238.

TP-472N serves as a negative control probe for TP-472, which is a specific and effective BRD7 9 probe.

ETP-47037 is a potent inhibitor of the PI3Kα isoform (IC50: 0.99 nM) and inhibits the PI3Kβ (IC50: 49.2 nM), PI3Kδ (IC50: 7.13 nM) and PI3Kγ (IC50: 49.1 nM) isoforms. ETP-47037 has potential for telomere protection chemoregulation studies.

JTP-4819 is a potent and selective prolyl endopeptidase (PEP) inhibitor with potential for treating Alzheimer's disease. At nanomolar concentrations, it inhibited the degradation of substance P, arginine-vasopressin, and thyrotropin-releasing hormone by PEP in supernatants of the rat cerebral cortex and hippocampus. Repeated administration of JTP-4819 reversed the aging-induced decrease in brain substance P-like and thyrotropin-releasing hormone-like immunoreactivity, suggesting it may improve the imbalance of peptidergic neuronal systems that develops with senescence by inhibiting PEP activity. Additionally, JTP-4819 increased acetylcholine release from the frontal cortex and hippocampus, regions closely associated with memory, in both young and aged rats.

Tyropeptin A-4 is used as a proteasome inhibitor.

TP-064 is a potent and selective PRMT4 inhibitor, featuring an IC50 < 10nM for methylation of H3 (1-25) and over 100-fold selectivity compared to other histone methyltransferases and non-epigenetic targets. It inhibits the methylation of MED12 in cells with an IC50 of 43 nM.

4'-Azidothymidine 5'-triphosphate exerts selectively action on both reverse transcriptase of human immunodeficiency virus type 1 and human DNA polymerases alpha and beta.

Thymocartin (RGH 0206) is a fragment 32-35 of the naturally occurring thymic factor (thymopoietin).Thymocartin is used in the study of immunodeficiency diseases.

6-Prenylindole is a bacterial metabolite that has been found in Streptomyces and has antifungal and antimalarial properties.1 It is active against A. brassicicola strain TP-F0423 and F. oxysporum f. sp. tulipae TU-4-2 (15 and 30 μg/disc in the paper disc assay), and also drug-resistant P. falciparum strain K1 (IC50 = 21 μg/ml).2 |1. Sasaki, T., Igarashi, Y., Ogawa, M., et al. Identification of 6-prenylindole as an antifungal metabolite of Streptomyces sp. TP-A0595 and synthesis and bioactivity of 6-substituted indoles. J. Antibiot. (Tokyo) 55(11), 1009-1012 (2002).|2. Nkunya, M.H., Makangara, J.J., and Jonker, S.A. Prenylindoles from Tanzanian Monodora and Isolona species. Nat. Prod. Res. 18(3), 253-258 (2004).

8-iso-15-keto Prostaglandin F2α (8-iso-15-keto PGF2α) is a metabolite of the isoprostane 8-iso PGF2α in rabbits, monkeys, and humans. 8-iso PGF2α is a prostaglandin-like product of non-specific lipid peroxidation. In humans and monkeys, exogenously infused 8-iso PGF2α is converted to metabolites with 2 or 4 carbon atoms removed from the top side chain by β-oxidation, with a similar pattern observed in tritiated 8-iso PGF2α-infused rabbits. Early in the infusion (within 1-2 minutes), 8-iso-15-keto PGF2α is a major component of the metabolite profile, primarily comprising unmetabolized 8-iso PGF2α. 8-iso-15-keto PGF2α is a vasoconstrictor when tested on the rat isolated thoracic aorta, acting via the TP (thromboxane) receptor.

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.

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.

Selective prostacyclin IP receptor antagonist (pKi = 8.3). Exhibits no affinity at other prostanoid receptors (EP1-4, FP and TP) in a radioligand binding assay. Demonstrates analgesic activity in rats. Orally bioavailable. Clark et al (2004) Discovery and SAR development of 2-(phenylamino) imidazolines as prostacyclin receptor antagonists. Bioorg.Med.Chem.Lett. 14 1053 PMID:15013022 |Jones et al (2006) Investigation of the prostacyclin (IP) receptor antagonist RO1138452 on isolated blood vessel and platelet preparations. Br.J.Pharmacol. 149 110 PMID:16880763 |Bley et al (2006) RO1138452 and RO3244794: characterization of structurally distinct, potent and selective IP (prostacyclin) receptor antagonists. Br.J.Pharmacol. 147 335 PMID:16331286

AL 8810 methyl ester, a prostaglandin F(2α) analog and receptor agonist, competitively antagonizes FP receptor agonist Fluprostenol effects. It lacks significant potency against TP, DP, EP(2), EP(4) receptor subtypes in cell lines [1].