concentration ratio

4-Hydroxyantipyrine is formed during oxidative deamination of aminopyrine.

AGI-026 (AGI-12026) is a novel and potent dual inhibitor of the mutant isocitrate dehydrogenase mIDH1 2 with the advantages of oral administration and penetration of the blood-brain barrier, with a drug concentration to plasma concentration ratio (brain plasma ratio) of 1.5 in brain tissue, and the ability to reduce the accumulation of the carcinogenic metabolite d-2-hydroxyglutarate (2-HG), which is used in the study of mIDH gliomas.

Antimicrobial agent-34 (compound 4h), characterized by its clogP value of 9.14, effectively disrupts the integrity of bacterial cell membranes. This compound boasts a minimum inhibitory concentration (MIC) ranging from 1–4 μg mL and shows notable plasma stability with an HC50 of 131.1 μg mL. Additionally, it exhibits excellent membrane selectivity, as evidenced by its HC50 MIC ratio of 65.6, and possesses rapid sterilization capabilities. It not only increases intracellular reactive oxygen species but also causes the leakage of protein and DNA, culminating in bacterial death. Antimicrobial agent-34 has demonstrated significant antibacterial effectiveness in vivo, particularly in a mouse sepsis model infected with Staphylococcus aureus ATCC43300.

M4K2281 is a potent and selective inhibitor of ALK2 with a half-maximal inhibitory concentration (IC50) of 2 nanomolar. In both biochemical and cellular assays, M4K2281 and M4K2308 demonstrate strong efficacy against ALK2. Moreover, M4K2281 exhibits a brain-to-plasma ratio that ranges from moderate to high.

MitoA is a ratiometric mass spectrometry probe that can be used for assessing changes in H2S within mitochondria in vivo. MitoA contains a triphenylphosphonium cation component that drives its accumulation in mitochondria where its aryl azide moiety selectively reacts with H2S to produce an amine product, MitoN. Quantifying the MitoN/MitoA ratio by LC-MS/MS reflects the mitochondrial matrix H2S concentration. In a mouse model of acute myocardial infarction with MitoA administered prior to ischemia, the MitoN/MitoA ratio is increased only in the region of ischemia.

MitoP is a phenol product produced by the reaction of H2O2 with the ratiometric mass spectrometry probe MitoB . MitoB contains a triphenylphosphonium cation component that drives its accumulation in mitochondria where its arylboronic moiety selectively reacts with H2O2 to produce MitoP. Quantifying the MitoP/MitoB ratio by LC-MS/MS reflects the mitochondrial matrix H2O2 concentration.

Sphingosines are long-chain base precursors of cellular sphingolipids used directly in the synthesis of ceramide, which in combination with sialic acid forms ganglioside. Sphingosine can exist in four stereoisomers, however only sphingosine occurs naturally. Compared to other sphingolipids throughout the body, which are predominantly composed of C-18 sphingosine, only central nervous system (CNS) gangliosides contain significant amounts of sphingosine. The concentration of sphingosine within mammalian brain gangliosides apparently increases with developmental maturation. Furthermore, the ratio of C-18 to C-20 sphingosine in the brain is thought to be related to some nervous system degeneration processes.

PKM2 activator 3 is a highly potent compound that activates PKM2, with an AC 50 value of 90 nM. It exhibits excellent Caco-2 permeability, a low efflux ratio, and remarkable microsomal stability. PKM2 activator 3 is particularly valuable for anticancer research purposes [1]. (AC 50: the concentration at which 50% enzyme activation occurs.)

α-Synuclein inhibitor 4 (compound 3gh) is a highly effective, blood-brain barrier-permeable inhibitor of α-Synuclein aggregation, demonstrating potent activity with an IC50 value of 0.98 μM and an inhibition ratio of 91.2% at 30 μM [1].

The growth factors, platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) play major roles in enhanced smooth muscle cells growth in rodent blood vessels after vascular injury. Tyrosine kinase inhibition has been shown to be effective in blocking tyrosine phosphorylation at the PDGF and bFGF receptors in cultured fibroblast and vascular smooth muscle cells which in turn inhibits their proliferation[1]. CGP 53716 is a specific PDGFR tyrosine kinase inhibitor on SMC (smooth muscle cell) proliferation and migration in vitro and in neointimal formationin vivo[3]. CGP 53716 inhibited serum-induced cell growth in RASMC (rat aortic smooth muscle cells). And it completely blocked PDGF-BB tyrosine receptor autophosphorylation in RASMC and 3T3 cells, PDGF-BB-induced phosphorylation of mitogen-activated protein kinase at 1 μM in RASMC and inhibited PDGF-BB-induced c-Fos protein expression at 1 μM in RASMC; consistent with inhibition of PDGF-BB-induced DNA synthesis. Further, CGP 53716 inhibited PDGF-BB-, bFGF- and EGF-induced DNA synthesis in a concentration-dependent manner in each cell line. And it showed a 2- to 4-fold selectivity for PDGF-BB-stimulated DNA synthesis over bFGF or EGF in RASMC or 3T3 cells[1]. CGP 53716 inhibited dose dependently tyrosine phosphorylation of both the known PDGFRs: the PDGFR-α and PDGFR-β. After rat carotid artery ballooning injuryin vivo, the migration of alpha-actin-positive cells on the luminal side of internal elastic lamina was decreased with 50 mg kg day of CGP 53716 from 38 ± 10 (control group) to 4 ± 2. Intima media ratio was inhibited by 40% after 14 days in the CGP 53716-treated group (P=0.028) after rat aortic denudation[3].

Arsthinol is an antiprotozoal agent which may have anti-cancer activity. It was found that arsthinol, a trivalent organoarsenic compound (dithiarsolane), has been active in vitro on leukemia cell lines and offers a better therapeutic index than arsenic trioxide, as estimated by the ratio LD50 IC50. Arsthinol induced growth inhibition of NB4 cells at lower concentration (IC50 (concentration inhibiting growth by 50%) = 0.78 + - 0.08 micromol l after 24 h) than As(2)O(3) (IC50 = 1.60 + - 0.23 micromol l after 24 h) or melarsoprol (IC50 = 1.44 + - 0.08 micromol l after 24 h). Arsthinol-cyclodextrin complex demonstrated to have was more effective than arsenic trioxide (As2O3) and melarsoprol on the U87 MG cell line. Importantly, in the in vivo study, significant antitumor activity against heterotopic xenografts was observed after i.p. administration.

This novel compound is an orally bioavailable antagonist of P2X3 P2X2 3 receptors, exhibiting potent activity with a pIC50 of 8 in both human and rat, and a pIC50 of 7.3 specifically for the human P2X2 3 receptor. It demonstrates high brain penetration, evidenced by a brain to plasma ratio of 6, and effectively blocks agonist-evoked intracellular Ca2+ flux and inward currents within the nanomolar range (10 nM to 1 µM) in cell lines that express human P2X3 and P2X2 3 receptors recombinantly. The compound also shows favorable pharmacokinetic properties, with a half-life (t1 2) of 1.63 hours and a time to reach maximum concentration (Tmax) of 30 minutes.

Sterculic acid methyl ester, an ester derivative of sterculic acid known for inhibiting Δ9 desaturase, has been found to adversely affect and exhibit toxicity towards R. opacus bacteria at a concentration of 0.75 mM. It not only hampers bacterial growth but also modifies fatty acid composition by reducing stearate and oleate levels, increasing the palmitate ratio, and decreasing overall fatty acid content at 0.25 or 0.5 mM concentrations. Additionally, at 50 ppm, Sterculic acid methyl ester enhances the tumor growth-promoting effects of aflatoxin Q1 in rainbow trout, indicating a synergistic interaction between the two compounds. [Matreya, LLC. Catalog No. 1236]

This novel compound is an orally bioavailable antagonist of P2X3/P2X2/3 receptors, exhibiting potent activity with a pIC50 of 8 in both human and rat, and a pIC50 of 7.3 specifically for the human P2X2/3 receptor. It demonstrates high brain penetration, evidenced by a brain to plasma ratio of 6, and effectively blocks agonist-evoked intracellular Ca2+ flux and inward currents within the nanomolar range (10 nM to 1 µM) in cell lines that express human P2X3 and P2X2/3 receptors recombinantly. The compound also shows favorable pharmacokinetic properties, with a half-life (t1/2) of 1.63 hours and a time to reach maximum concentration (Tmax) of 30 minutes.

20-Hydroxylucidenic acid E2 is a triterpene compound identified in Ganoderma ludicum. It significantly inhibits TPA-induced inflammation and suppresses TPA-induced EBV early antigen expression with an IC50 of 290 mol ratio 32 pmol TPA [indicating that the molar concentration of this compound is 290 times that of TPA (32 pmol) to achieve 50% inhibition of EBV early antigen expression]. This compound is applicable in anti-inflammatory and anticancer research.