Metabolism

Ro 31-8472 is an angiotensin-converting enzyme (ACE) inhibitor and an analog of cilazaprilat.

β-Glucuronidase/hCAII-IN-2 is a potent inhibitor of β-glucuronidase and hCA II, and their IC50 values were 670.7 μM and 21.77 μM, respectively.

EpoY (SD-142) is an irreversible inhibitor of the primary brain microtubule-associated tyrosine carboxypeptidase (TCP), a complex formed by vasohibin-1 (VASH1) and small vasohibin-binding protein (SVBP). By inhibiting TCP with an IC50 value of approximately 500 nM, EpoY effectively reduces the levels of detyrosinated α-tubulin, which is crucial for microtubule dynamics and neuronal differentiation. This inhibition results in significant differentiation defects and is linked to potential issues related to cancer and cardiomyopathy.

GC-IN-2 (Compound 25) is an effective and selective non-sugar-based glucocerebrosidase inhibitor with an IC50 value of 6.46 μM. It is utilized in research related to Gaucher's disease.

15-epi-PGE1 (15R-Prostaglandin E1; 15-Epiprostaglandin E1), a stereoisomer of PGE1, exhibits reduced biological activity [2]. This compound acts as a non-competitive inhibitor of human placental 15-Hydroxyprostaglandin dehydrogenase (15-PGDH), with an inhibitory concentration 50 (IC50) value of 170 μM [1].

Pefcalcitol is a novel antipsoriatic prodrug candidate containing a 16-en-22-oxa-vitamin D3 structure.

(3S,17S)-FD-895 is an analogue of FD-895. It inhibits the growth of HCT116 cells and shows splicing-modulating activity. This compound can be utilized in cancer research.

3β,7β-Dihydroxy-5-cholestenoic acid is a C27 acid whose levels are elevated in Niemann-Pick Type C and B diseases, leading to toxicity in ocular motor neurons. It is synthesized by the enzymatic action of hydroxysteroid 11-β dehydrogenase 1 from 3β-hydroxy-7-oxocholest-5-en-(25R)26-enoic acid (3βH,7O-CA).

RORγt modulator 5, a potent RORγt modulator, exhibits a dissociation constant (K_i) of <100 nM.

PDE5-IN-8 (compound 2) is an inhibitor of PDEs.

Sekikaic acid, a phenolic lichen metabolite in H. obscurata, has antioxidant and antiviral properties, inhibiting MLL1-CBP.

CIT-ALD is an aldehyde intermediate formed during the metabolism of Citalopram. It has potential applications in the research of neurological disorders.

L-Phenylalanyl-L-threonine is a dipeptide composed of phenylalanine and threonine, which can be utilized in the synthesis of the cyclic hexapeptide [Banyascyclamide A].

Fluopimomide (LH2010A), a powerful insecticide, is extensively utilized in the control of agricultural pests. It adversely affects the growth, locomotor behavior, reproduction, and lifespan of nematodes. Concurrently, it leads to increased production of reactive oxygen species (ROS), accumulation of lipids and lipofuscins, as well as a rise in malondialdehyde content. Additionally, Fluopimomide inhibits the antioxidant system of nematodes.

7-Hydroxychlorpromazine, an active metabolite of Chlorpromazine, can reversibly counteract the suppression of regionally dense dopaminergic neurons induced by Amphetamine.

PDEδ-IN-1 is a ligand for PDEδ and can be utilized in the synthesis of PDEδ autophagic degrader 1.

Complex III-IN-1 inhibits complex III, has antifungal properties, and an EC50 of 18.53 mg/L against S. sclerotiorum.

PF-00489791 (PF4634817) is a long-acting PDE5 inhibitor with hypotensive activity for the study of diabetic nephropathy.

1-Phenylethanamine, a potential central nervous system stimulant related to β-phenylethylamine (β-phenylethylamine), exhibits diminished glycogenolysis activity in the brain due to its benzene ring being replaced by an indole group. This reduction in activity makes it useful for investigating how the chemical structure of phenylethylamine derivatives influences their effects on the central nervous system. Additionally, 1-Phenylethanamine is also utilized in the synthesis of the tyrosine kinase (tyrosine kinase) inhibitor CLM3.

RO5101576 is a potent antagonist of LTB4 receptor.

hCAII-IN-4 (Compound 12j) is a potent inhibitor of human carbonic anhydrase II (hCA II), exhibiting an inhibitory concentration (IC50) of 7.78 μM.

FAAH/MAGL-IN-3 irreversibly inhibits FAAH (IC50: 179 nM) & MAGL (IC50: 759 nM) with low PAMPA permeability.

Compound S1 (antidiabetic agent 5) is an antidiabetic agent that effectively inhibits the enzymes α-glucosidase and α-amylase, demonstrating IC50 values of 3.91 µM and 8.89 µM, respectively. It reduces sugar levels and holds potential for type-II diabetes research [1].

FXIa-IN-9, a potent FXIa inhibitor (K i : human 0.17 nM, rabbit 0.5 nM), forms hydrogen bonds and has anticoagulant properties.

Tovinontrine (IMR-687) (IMR-687) is a potent and selective inhibitor of phosphodiesterase-9 (PDE9), designed to target sickle cell disease treatment.

CAII-IN-2 (3g): potent, selective CA-II inhibitor; IC50-12.1 μM for bovine CA-II; valuable in CA-related disorder research.

IDX375 is a non-nucleoside inhibitor that selectively targets the HCV NS5B enzyme. It shows promising selectivity for genotypes 1a and 1b. The structure and binding sites of IDX375 have been confirmed through X-ray co-crystallization studies.

NTPDase-IN-3 inhibits NTPDase1/2/3/8 (IC50: 0.21/1.07/0.38/0.05 μM), useful for cancer and thrombosis research.

(S)-Dexfadrostat ((S)-Fadrozole), an aromatase inhibitor, exhibits an IC 50 of 4.6 nM in in vitro assays using human placental microsomes. It is applicable for research on estrogen-dependent breast cancer, gynecomastia, and systemic lupus erythematosus.

Mitochondrial-IN (C458) is a potent inhibitor of mitochondrial complex I. It offers significant protection against Aβ toxicity, exhibits favorable pharmacokinetic properties, and has minimal off-target effects.

hCAIX-IN-20 (compound APBS-5m) is a potent inhibitor of carbonic anhydrase IX (hCA IX), with a Ki of 2.7 nM, playing a significant role in cancer research.

hCAIX/XII-IN-15 (Compound 17β) is an inhibitor of hCA IX and hCA XII, exhibiting Ki values of 0.42 and 4.37 μM, respectively. It demonstrates a pro-apoptotic effect in multiple myeloma cells.

7-Hydroxy-4-phenylcoumarin is a dual inhibitor of ALDH-2 and MAO, with IC50 values of 1.5 µM and 0.5 µM, respectively.

ATUX-1215, a protein phosphatase 2A (PP2A) activator, diminishes the phosphorylation of ERK, p38, JNK, and Akt, as well as decreases the secretion of IL-12p70,

ACLY-IN-1 (compound 55) is a potent ACLY inhibitor with an IC50 of 8.3 nM, and it can be utilized in hyperlipidemia research.

Anticancer agent 78: anti-aromatase (IC50=0.9 μM), cytotoxic, potential in breast cancer research.

17β-HSD1-IN-1 (Compound 1) can be used in the non-small cell lung cancer (NSCLC) research.

Lipid PPz-2R1 is an ionizable cationic lipid employed in crafting lipid nanoparticles (LNPs) for mRNA delivery both in vitro and in vivo. LNPs with lipid PPz-2R1, encapsulating an mRNA reporter, target the lungs preferentially over the heart, liver, spleen, and kidneys in mice. Additionally, these LNPs, when encapsulating mRNA encoding phosphatase and tensin homolog (PTEN), enhance PTEN protein levels in PTEN-deficient Lewis lung carcinoma (LLC) cells. In an orthotopic murine LLC model, these Lipid PPz-2R1-containing LNPs, carrying PTEN mRNA, reduce tumor growth either when administered alone or alongside an antibody against programmed cell death protein 1 (PD-1).

HSD17B13-IN-40 (compound 6) serves as a potent inhibitor of hydroxysteroid 17β-dehydrogenase 13 (HSD17B13), exhibiting an IC50 value of less than 0.1 μM using estradiol as substrates. This compound is significant in the treatment of nonalcoholic fatty liver diseases (NAFLDs), including nonalcoholic steatohepatitis (NASH) [1].

Phocaecholic acid, a bile acid, has been identified in the bile of ducks (A. platyrhynchos).

Nampt-IN-14 (example 3) is an effective NAMPT inhibitor with an IC50 of 0.2 nM, suited for use in the synthesis of antibody-drug conjugates (ADCs).

MAGL-IN-19 (compound 7o) is a highly effective and selective inhibitor of MAGL.

Nsp12-IN-2 (Compound 8), a triphosphate metabolite of 4'-thiouridine, functions as an inhibitor of SARS-CoV-2 Nsp12. It effectively suppresses the RNA-dependent RNA polymerase (RdRp) activity of the SARS-CoV-2 Nsp12-Nsp7-Nsp8 complex, halting RNA synthesis and blocking the RNA capping and NMP capping of Nsp9. Nsp12-IN-2 shows potential for research into infections caused by SARS-CoV-2, other coronaviruses, and additional RNA viruses.

FXIa-6f is a high affinity, orally bioavailable macrocyclic FXIa inhibitor with antithrombotic activity in preclinical species

IMR687: a PDE9 inhibitor that could improve memory in Alzheimer's by slowing cGMP hydrolysis.

Salacinol is a naturally occurring alpha-glucosidase inhibitor isolated from an Ayurvedic traditional medicine Salacia reticulata.

Ranolisib is an isocitrate dehydrogenase (IDH) inhibitor known for its antitumor activity.

<p>Morocromen is a 2-benzamidobenzoic acid derivative characterized by its ability to enhance coronary activity.</p>

HSD17B13-IN-19 (compound 16) acts as a potent inhibitor of hydroxysteroid 17β-dehydrogenase 13 (HSD17B13), exhibiting IC50 values under 0.1 μM and under 1 μM when using estradiol and Leukotriene B3 as substrates, respectively. This compound is crucial in the treatment of nonalcoholic fatty liver diseases (NAFLDs), such as nonalcoholic steatohepatitis (NASH) [1].

MAFP (Methyl Arachidonyl Fluorophosphonate) is an effective irreversible inhibitor of anandamide amidase.