tp 1

TP-030-1, an inhibitor of RIPK1, exhibits potent activity against hRIPK1 (human RIPK1) with a Ki value of 3.9 nM and against mRIPK1 (mouse RIPK1) with an IC50 value of 4.2 μM. This compound is instrumental in the research of inflammatory and neurodegenerative diseases.

TP receptor antagonist-1 (compound 7m) serves as an antagonist for the thromboxane A2 receptor (TP receptor), exhibiting IC50 values of 9.46 μM for TPa and 8.49 μM for TPb. It is utilized in the study of cardiovascular diseases [1].

JTP 103237 is a potent and selective monoacyglycerol acyltransferase 2 (MOGAT2) inhibitor.

EFdA-TP 3TEA is the salt form of EFdA-TP.EFdA-TP 3TEA is a nucleoside analog that is a novel, potent, and selective nucleoside reverse transcriptase (RT) inhibitor that inhibits HIV-1 reverse transcriptase by multiple mechanisms, thereby increasing its drug resistance.

1-Methylxanthine is a caffeine derivative. 1-Methylxanthine is an essential human urinary metabolite of caffeine and theophylline (1,3-dimethylxanthine, TP). 1-Methylxanthine enhances the radiosensitivity of tumor cells.

L 888607 Racemate is a selective antagonist of the prostaglandin D2 receptor subtype 1 (DP1) with Ki values of 132 nM and 17 nM for DP1 and the thromboxane A2 receptor (TP), respectively.

BW A868C, a hydantoin compound and structural analogue of BW245C, functions as a selective and potent competitive antagonist of prostaglandin D2 (PGD2), showing no activity on other prostaglandin receptors (IP, EP1, EP2, TP, and FP) [1].

R-82913 is a RNA-directed DNA polymerase inhibitor. R 82913 reduce 5-HT2 receptor-mediated DOI-head-shakes in mice. R82913 inhibited the replication of thirteen different strains of HIV-1 in CEM cells with a median IC50 of 0.15 microM. R82913 was 20-fold

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.

TP-238, a potent and selective dual CECR2 BPTF probe, exhibits IC50 values of 30 nM and 350 nM, respectively. Additionally, it inhibits BRD9 with a pIC50 of 5.9, demonstrating lesser activity against another 338 kinases [1] [2].

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).

EFdA-TP tetraammonium is an influential nucleoside reverse transcriptase (RT) inhibitor that effectively prevents RT-mediated DNA synthesis by acting as an immediate or delayed chain terminator (ICT or DCT). Additionally, EFdA-TP tetraammonium exhibits multiple mechanisms of inhibiting HIV-1 RT[1].

Beauvericin A is a cyclodepsipeptide and derivative of beauvericin originally isolated fromB. bassianathat has diverse biological activities.1,2,3It is active againstM. tuberculosis(MIC = 25 μg/ml) andP. falciparum(IC50= 12 μg/ml).2Beauvericin A is toxic to brine shrimp (LD100= 32 μg/ml).3 1.Gupta, S., Montillor, C., and Hwang, Y.-S.Isolation of Novel Beauvericin Analogues from the Fungus Beauveria bassianaJ. Nat. Prod.58(5)733-738(1995) 2.Nilanonta, C., Isaka, M., Kittakoop, P., et al.Antimycobacterial and antiplasmodial cyclodepsipeptides from the insect pathogenic fungus Paecilomyces tenuipes BCC 1614Planta Med.66(8)756-758(2000) 3.Shi, S., Li, Y., Ming, Y., et al.Biological activity and chemical composition of the endophytic fungus Fusarium sp. TP-G1 obtained from the root of Dendrobium officinale Kimura et MigoRec. Nat. Prod.12(6)549-556(2018)

8-iso PGF3α is an isoprostane produced from the free-radical peroxidation of EPA. While little is known about its biological activity, one report indicates it is inactive in a TP receptor-mediated assay of human platelet shape change, a test in which 8-iso PGF2α has an ED50 value of 1 uM. [1]

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.

AZT triphosphate TFA (3'-Azido-3'-deoxythymidine-5'-triphosphate TFA) is a active triphosphate metabolite of Zidovudine (AZT). AZT triphosphate TFA exhibits antiretroviral activity and inhibits replication of HIV. AZT triphosphate TFA also inhibits the DNA polymerase of HBV. AZT triphosphate TFA activates the mitochondria-mediated apoptosis pathway[1][2][3]. Treatment with 100 μM Zidovudine (AZT) for 48h disrupts the mitochondrial tubular network via accumulation of AZT triphosphate (AZT-TP) in H9c2 cells. AZT triphosphate accumulation causes downregulation of Opa1 and upregulation of Drp1. AZT triphosphate causes mitochondrial dysfunction, increases the production of cytotoxic reactive oxygen species (ROS), and impairs the balance of the mitochondrial quality control system in H9c2 cell model established from rat embryonic myoblasts[1]. [1]. Ryosuke Nomura, et al. Azidothymidine-triphosphate Impairs Mitochondrial Dynamics by Disrupting the Quality Control System. Redox Biol. 2017 Oct;13:407-417. [2]. Takeya Sato, et al. Engineered Human tmpk/AZT as a Novel Enzyme/Prodrug Axis for Suicide Gene Therapy. Mol Ther. 2007 May;15(5):962-70. [3]. K Y Hostetler, et al. Enhanced Oral Absorption and Antiviral Activity of 1-O-octadecyl-sn-glycero-3-phospho-acyclovir and Related Compounds in Hepatitis B Virus Infection, in Vitro. Biochem Pharmacol. 1997 Jun 15;53(12):1815-22.

Prostaglandin B2 (PGB2) is a non-enzymatic dehydration product resulting from the treatment of PGE2 or PGA2 with strong base. It has weak agonist activity on TP receptors and can increase pulmonary blood pressure in the rabbit at relatively high doses (5 ug/kg). [1]

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.

EFdA-TP, a highly potent nucleoside reverse transcriptase (RT) inhibitor, exerts its inhibitory effect on RT-catalyzed DNA synthesis through both immediate and delayed chain termination mechanisms, commonly referred to as ICT and DCT, respectively. Additionally, EFdA-TP demonstrates its efficacy in inhibiting HIV-1 RT through multiple pathways.

TP-3654, a second-generation Pim kinase inhibitor (Ki values against Pim-1 3: 5 42 nM).

Treprostinil Sodium (UT-15) is a potent DP1, IP and EP2 agonist (EC50: 0.6 1.9 6.2 nM).

TP-110 is a new proteasome inhibitor, which shows potent growth inhibition in various tumor cell lines. Treatment with TP-110 for 24 h in vitro induced apoptosis in multiple myeloma cell line RPMI8226. TP-110 reduced the intrinsic inhibitor of apoptosis proteins (IAPs), cIAP-1 and XIAP, that suppress executioner caspases.

EFdA-TP tetrasodium, a potent nucleoside reverse transcriptase (RT) inhibitor, effectively halts RT-catalyzed DNA synthesis by acting as an immediate or delayed chain terminator (ICT or DCT). It employs multiple mechanisms to inhibit HIV-1 RT [1].

TP-030-2 is a RIPK1 inhibitor with a human Ki of 0.43 nM and a mouse IC50 of 100 nM.