(2-Pyridyldithio)-PEG4 acid is a four-unit cleavable polyethylene glycol (PEG) linker specifically designed for the synthesis of antibody-drug conjugates (ADCs)[1]. It serves as a crucial component in the conjugation of antibodies and drugs, enabling targeted drug delivery and enhanced therapeutic efficacy. This linker possesses a (2-pyridyldithio) group at one end, facilitating the attachment of the linker to the specific site on the antibody molecule. The PEG4 chain provides the necessary flexibility and biocompatibility for optimal drug release while maintaining stability throughout the circulation in the body. Ultimately, (2-Pyridyldithio)-PEG4 acid is instrumental in the development and advancement of ADCs, a promising approach in cancer therapy.
AGN-201904Z is a slowly absorbed, acid-stable pro-proton pump inhibitor (pro-PPI) rapidly converted to omeprazole in the systemic circulation giving a prolonged residence time. AGN 201904-Z produced a significantly greater, and nocturnal acid suppression
Levomefolate magnesium is the magnesium salt of the metabolite of folic acid (Vitamin B9) and it is a predominant active form of folate found in foods and in the blood circulation, accounting for 98% of folates in human plasma. It is transported across th
Peroxidation of common ω-6 polyunsaturated fatty acids (PUFAs) such as linoleic acid, DGLA, and arachidonic acid can give rise to 4-HNE. 4-HNE is cleared rapidly from the plasma and undergoes enterohepatic circulation as a glutathione conjugate in the rat. About two thirds of an administered dose of 4-HNE is excreted within 48 hours in the urine, primarily in the form of mercapturic acid conjugates. The C-1 aldehyde of 4-HNE is reduced to an alcohol in about half of these metabolites. The remainder are C-1 aldehydes or have been oxidized to C-1 carboxylic acids. These aldehydes and carboxylic acids can also form γ-lactols and γ-lactones, respectively, producing at least 4 or 5 end urinary metabolites of 4-HNE in vivo.
Thromboxane B2 (TXB2) is released in substantial quantities from aggregating platelets and metabolized during circulation to 11-dehydro TXB2 and 2,3-dinor TXB2. In rats and rabbits, 2,3-dinor TXB1 has been identified as another urinary metabolite of TXB2. However in human urine, only trace amounts of 2,3-dinor TXB1 have been identified. In rats, 2,3-dinor TXB1 is excreted at a much higher rate than 2,3-dinor TXB2 (19.2 ± 4.9 ng/24 hr and 1.6 ± 0.3 ng/24 hr, respectively). Therefore, urinary 2,3-dinor TXB1 is a suitable marker of thromboxane biosynthesis in rats.
Echistatin TFA, the smallest active RGD protein belonging to the family of disintegrins that are derived from snake venoms, is a potent inhibitor of platelet aggregation. Echistatin is a potent inhibitor of bone resorption in culture. Echistatin is a potent antagonist of αIIbβ3, αvβ3 and α5β1[1][2][3][4]. [1]. J Musial, et al. Inhibition of platelet adhesion to surfaces of extracorporeal circuits by disintegrins. RGD-containing peptides from viper venoms. Circulation. 1990 Jul;82(1):261-73.[2]. M Sato, et al. Echistatin is a potent inhibitor of bone resorption in culture. J Cell Biol. 1990 Oct;111(4):1713-23.[3]. C C Kumar, et al. Biochemical characterization of the binding of echistatin to integrin alphavbeta3 receptor. J Pharmacol Exp Ther. 1997 Nov;283(2):843-53.[4]. I Wierzbicka-Patynowski, et al. Structural requirements of echistatin for the recognition of alpha(v)beta(3) and alpha(5)beta(1) integrins. J Biol Chem. 1999 Dec 31;274(53):37809-14.
Dichloroacetate (DCA) is an inhibitor of all pyruvate dehydrogenase kinase (PDHK) isoforms, which are enzymes that phosphorylate and inhibit PDH in mitochondria. Inhibition of PDHK shifts cell metabolism from glycolysis to mitochondrial glucose oxidation, an effect that has relevance to cancer, type 2 diabetes, and other diseases. CAY10703 is a DCA trimer that is at least 10-fold more cytotoxic against leukemia cell lines than DCA. It is approximately 3-fold less cytotoxic than DCA against peripheral blood mononuclear cells from healthy blood donors. CAY10703 significantly reduces both basal and maximal respiration in leukemia cells. It is stable in vivo after subcutaneous inoculation, remaining in circulation for more than five hours after injection.
Synthetic and natural alkyl phosphates, also known as phosphoantigens, stimulate the proliferation of γδ-T lymphocytes. Isopentenyl pyrophosphate, and related derivatives including (E)-hydroxy-dimethyl-allyl pyrophosphate ((E)-HDMAPP), are particularly effective activators of γδ-T cells. (E)-C-HDMAPP is the pyrophosphonate form of (E)-HDMAPP. The pyrophosphonate moiety in (E)-C-HDMAPP is much less susceptible to chemical or enzymatic hydrolysis than its pyrophosphate counterpart. As a result, (E)-C-HDMAPP is much more stable in solution and in vascular circulation. (E)-C-HDMAPP possesses comparable activity to (E)-HDMAPP, which is the most potent of the isoprenoid phosphoantigens. (E)-C-HDMAPP stimulates the synthesis of tumor necrosis factor (TNF-α) by γδ-T lymphocytes with an IC50 value of 0.91 nM. (E)-C-HDMAPP also significantly increases the number of circulating γδ-T cells in vivo, in cynomolgus monkeys.
(2-Pyridyldithio)-PEG1-hydrazine is a one-unit cleavable polyethylene glycol (PEG) linker specifically designed for the synthesis of antibody-drug conjugates (ADCs). This linker offers the advantage of controlled release of the drug payload from the ADC construct. It is utilized in the conjugation process between the antibody and the cytotoxic drug, enabling the targeted delivery of the drug to cancer cells. The (2-pyridyldithio) group of this linker provides stability during circulation in the bloodstream, while the hydrazine moiety allows for efficient drug release at the tumor site. Overall, the (2-pyridyldithio)-PEG1-hydrazine linker serves as a valuable tool in the development of targeted chemotherapeutic agents for cancer treatment.