Metabolism

JTE-151, a RORγ inhibitor, suppresses the overactive immune response by inhibiting RORγ, which is linked to the activation of Th17 cells. This action positions JTE-151 as a potential candidate for autoimmune disease research [1].

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

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.

Erizepine, an octopamine receptor 3 (OAR3) antagonist, exhibits a Ki value of 474 nM. This compound is utilized in insect research.

Vimirogant is a RORγ inhibitor (Ki: <100 nM).

Myxothiazol blocks mitochondrial complex III and triggers SESN2, a gene important for stress response.

Carbonic anhydrase inhibitor 17 (compound 7c) is a pyrazine-based sulfonamide that acts as a carbonic anhydrase II inhibitor, with an IC50 value of 0.63 nM.

The PKR Inhibitor, negative control, is an inactive structural analog of RNA-dependent protein kinase (PKR) inhibitors, serving as a negative control. Additionally, it can inhibit LK-induced neuronal death, demonstrating significant neuroprotective properties.

α-Amylase-IN-7 (Compound 6e) is an inhibitor of α-Amylase, with an IC50 of 40 μM, indicating its potency. This compound shows potential as an anti-diabetic medication.

L 668411, the 2,3-ditritiated methyl ester of L 659699, inhibits HMG-CoA synthase.

SCP1-IN-2: potent, selective SCP1 inhibitor; induces REST degradation, hinders its activity, may study REST-driven glioblastoma growth.

L 671776 is an inositol monophosphatase inhibitor.

ICMT-IN-55 (compound 31) acts as an ICMT inhibitor, exhibiting an IC50 value of 90 nM [1].

α-Amylase/α-Glucosidase-IN-7 (Compound 3f) serves as a competitive inhibitor for the enzymes α-glucosidase and α-amylase, exhibiting IC50 values of 18.52 µM and 20.25 µM, respectively. Additionally, it effectively inhibits AChE and BChE, with IC50 values of 9.25 µM and 10.06 µM, respectively. This compound is useful in research related to diabetes and Alzheimer's [1].

LXRα agonist 1 (Compound 40) is a selective activator of LXRα, with an EC50 of 42 nM, and also demonstrates some activation effects on LXRβ, with an EC50 of 266 nM. It promotes target gene transcription by stabilizing the ligand-binding domain (LBD) of LXRα. When combined with the Raf inhibitor Sorafenib, LXRα agonist 1 shows significant antitumor activity in liver cancer cells. This compound is applicable in research focused on lipotoxicity-related cancers.

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.

Nomelidine, the active N-demethylated metabolite of zimelidine, has been used as an antidepressant and analgesic.

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.

Epoxykynin is a potent soluble epoxide hydrolase (sEH) inhibitor [1].

LTA4H-IN-3 (compound 9) functions as an inhibitor of LTA4H, demonstrating an IC50 of 28 nM [1].

(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.

UGT1A1-IN-1 (compound 2) acts as a non-competitive inhibitor of UGT1A1, effectively inhibiting the 1-O-glucuronidation process mediated by UGT1A1 with a Ki value of 5.02 μM. This compound binds to the same ligand-binding site on UGT1A1 as bilirubin and additionally functions as a 'turn-on' fluorescent probe substrate for UGT1A1 [1].

(+)-Potassium Ds-threo-isocitrate monobasic is a bioactive compound known for its role in enhancing cellular metabolism and regulating energy production. This substance is also utilized in researching metabolic pathways and the regulation of enzyme activities. Widely applied in biochemical research, (+)-Potassium Ds-threo-isocitrate monobasic is studied for its potential functions in cellular processes and disease mechanisms.

TAK-915: potent, brain-ready PDE2A inhibitor, 0.61 nM IC50, 4100x selectivity over PDE1A.

Glucosylceramide Synthase-IN-4 (compound 12) serves as a potent inhibitor of glucosylceramide synthase (GCS), exhibiting an IC50 of 6.8 nM. It demonstrates superior pharmacokinetic properties and robust stability in human hepatocytes. Additionally, this compound is noted for its effective CNS penetration and acceptable PXR selectivity [1].

O-Desmethyl Brinzolamide hydrochloride (compound 6a), a potent metabolite derived from Brinzolamide, serves as a carbonic anhydrase (CA) inhibitor. It exhibits a dissociation constant (Kd) of 0.136 nM for CA II and an inhibitory concentration (IC50) of 165 nM for CA IV [1].

α-Glucosidase-IN-63 (Compound 4d) serves as an α-Glucosidase inhibitor with an IC 50 value of 0.44 μM. Additionally, it exhibits inhibitory activity against hCA II, demonstrating a K i of 7.0 nM. The compound is also effective when administered orally. [1]

ABCB1-IN-4 (Compound C6z) is an orally active inhibitor of α-amylase and α-glucosidase, with IC50 values of 1.63 μM and 0.14 μM, respectively. It holds potential for diabetes research.

1-Stearoyl-sn-glycerol 3-phosphate sodium, a biologically active phospholipid, plays a crucial role in regulating cell motility, proliferation, invasion, survival, and the production of growth factors through interactions with G protein-coupled receptors (GPCR). Synthesized during the formation of membrane phospholipids, this compound typically has a low plasma concentration (approximately 100nM) and originates from various cell types, including activated platelets, epithelial cells, leukocytes, neuronal cells, and tumor cells. Its distinctive structure features stearic acid at the sn-1 position and a hydroxyl group at the sn-2 position.

Glucosylceramide synthase-IN-3 (BZ1) is a potent, brain-accessible, oral GCS inhibitor with a 16 nM IC50, relevant for Gaucher's disease study.

7α,24(S)-Dihydroxycholesterol ((3β,7α,24S)-Cholest-5-ene-3,7,24-triol) acts as a ligand for liver X receptors (LXR), specifically binding to the ligand-binding domains of LXRα and LXRβ. This compound is synthesized through the E-α,β-unsaturated ketone process, starting with arsindole and J-secondary-butyl dimethylsiloxy-bis-positive-5-cholestenal as the initial materials. It undergoes a series of transformations to produce 7α,24(S)-dihydroxycholesterol.

3-Ferrocenylpropionic anhydride is extensively used in compound synthesis, serving as an intermediary for producing various bioactive compounds. Additionally, by modulating specific enzyme activities, 3-Ferrocenylpropionic anhydride has demonstrated potential anti-tumor properties.

9-cis-β-Carotene, a precursor of retinal, is cleaved by beta-carotene oxygenase 1 (BCMO1) to produce 9-cis-retinal.

GSK864 is an inhibitor of isocitrate dehydrogenase 1 (IDH1) mutant. GSK864 inhibits IDH1 mutants R132C, R132H, and R132G (IC50: 8.8, 15.2, and 16.6 nM).

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).

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

Lp-PLA2-IN-6: Potent tetracyclic inhibitor of rhLp-PLA2, with pIC50 of 10.0, and potential in neurodegenerative research.

NSC 828467 is one of the top five CA-IX inhibitors with significant in vitro anticancer activity (IC50: 27.2 nM).

HSD17B13-IN-32 (Compound 67) is an inhibitor of hydroxysteroid 17β-dehydrogenase 13 (HSD17B13) with an IC50 value of ≤0.1 μM for estradiol. It can be used for research on liver diseases, metabolic diseases, or cardiovascular diseases, such as NAFLD or NASH, as well as drug-induced liver injury (DILI) [1].

2-Amino-5-methyl-5-hexenoic acid ((S)-2-Amino-5-methylhex-5-enoic acid) acts as a methionine analog, competing with methionine and thereby hindering cell growth. This compound inhibits protein synthesis in Salmonella typhimurium TA1535 and Escherichia coli K-12 without affecting the synthesis of DNA or RNA.

OH-α-PVP (OH-α-Pyrrolidinovalerophenone) TFA is a metabolite of α-pyrrolidinovalerophenone, which is a synthetic cathinone stimulant.

RORγt Inverse agonist 2 is a selective, orally active inverse agonist of RORγt(EC50 of 119 nM).

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

LXR agonist 2 is a potent agonist of the LXR (liver X receptor). LXR agonist 2 stabilises NCOA1 (coactivator), which in turn agonises the LXR.

MDL-100240 inhibits ACE/neprilysin, effective against hypertension-induced heart/vascular changes.

Norfluoxetine, the active metabolite of the antidepressant Fluoxetine, acts as a selective inhibitor for serotonin uptake.

Turoctocog alfa: recombinant FVIII from CHO cells for hemophilia A study.

α-Amylase-IN-10 (Compound 15n) is an inhibitor of α-Amylase, with an IC50 of 5.00 µM. This compound is applicable for research in type 2 diabetes.

Omesdafexor is an FXR agonist that can be used to study diseases caused by liver disease or metabolic inflammation.

Carbonic anhydrase inhibitor28 (Compound 11) serves as an inhibitor for the Pseudomonas aeruginosa carbonic anhydrase. It exhibits antibacterial activity, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 0.5 and 1 μg/mL, respectively, against P. aeruginosa. Carbonic anhydrase inhibitor28 is utilized in research focused on anti-infection applications.

ONL-1204 is a small molecule, CD95 antigen inhibitor (Fas inhibitor) being developed by ONL Therapeutics for the treatment of retinal detachment.

EB-0156: potent ER α-glucosidase inhibitor, IC50 of 0.0479/ <0.001 μM, N-substituted valerian, broad-spectrum antiviral potential.

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

Tauro-ω-muricholic acid sodium (TωMCA sodium) is an analogue of tauro-α-muricholic acid, a bile acid of hepatic origin.

Isoprostanes are produced by the non-enzymatic, free radical peroxidation of phospholipid-esterified arachidonic acid.

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].

PDE4-IN-14 (Compound 1) serves as an inhibitor of phosphodiesterase 4 (PDE4), applicable in research concerning diseases associated with PDE4, including

Dioctanoylphosphatidic acid sodium serves as a modulator of phagocyte respiratory bursts, a precursor to diacylglycerol and lyso-phosphatidic acid, and influences the phosphorylation of the mammalian target of rapamycin (mTOR). Additionally, it enhances the viability of gallbladder cancer cells inhibited by histone deacetylase inhibitors (HDACI). This compound is derived from glycerophospholipids through the action of phospholipase D.

(E)-10-Hydroxy Nortriptyline maleate, a derivative of antidepressant Nortriptyline, eases depression symptoms.

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

2,4-Dihydroxybutanoic acid is typically not found in extracts of normal human urine and is present only in trace amounts in newborns, while cases of succinic semialdehyde dehydrogenase deficiency consistently exhibit elevated levels of this metabolite.

BI-4916 is a phosphoglycerate dehydrogenase (PHGDH) inhibitor that inhibits SSP and reduces cancer cell migration.

BRD7539B: PfDHODH inhibitor, IC50 0.033μM; selective vs HsDHODH, IC50 >50μM.

LU 2443 is an orally active antiepileptic agent that is extensively absorbed, with up to 18% remaining unabsorbed in rats. The active half-life in plasma is 13.17 hours.

BMS-214662 mesylate is a potent and selective farnesyl transferase inhibitor with an IC50 of 1.35 nM. It exhibits antitumor activity and is applicable in cancer research.

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

RXR antagonist 2 is a potent antagonist of RXR (Ki: 0.391 μM, Kd: 0.281 μM). RXR antagonist 2 has shown research potential for RXR-related diseases.

PF-06795071 is an effective and selective covalent inhibitor of MAGL (IC50: 3 nM).

Fmoc-NH-PEG6-alcohol, a cleavable ADC linker, is employed in the synthesis of antibody-drug conjugates (ADCs) [1].

LXA5 is made from EPA by leukocytes, contracts guinea pig lungs like LXA4/LXB4, but doesn't dilate aorta.

HSD17B13-IN-28 (compound 47) is a potent inhibitor of hydroxysteroid 17β-dehydrogenase 13 (HSD17B13), with an IC50 of < 0.1 μM using estradiol as a substrate. HSD17B13-IN-28 plays an important role in nonalcoholic fatty liver diseases (NAFLDs), including NASH (nonalcoholic steatohepatitis) [1].

7-Hydroxyrisperidone (7-RispOH) is a metabolite of Risperidone. Risperidone acts as a 5-HT2 receptor blocker, an inhibitor of P-glycoprotein (P-Glycoprotein), and an antagonist of the dopamine D2 receptor.

Nampt-IN-15 (Example 3) is a Nampt inhibitor that exhibits cytotoxic effects on various cell lines, including BxPC-3, HepG2, L540cy, and MOLM-13. The respective IC50 values for these cell lines are 38.5 nM, 8 nM, 8.5 nM, and 7 nM.

(R)-Acenocoumarol ((R)-Acenocoumarin; (R)-Nicoumalone) is a short-acting, orally administered anticoagulant that works by inhibiting vitamin K epoxide reductase (vitamin K1 recycling), similar to Warfarin. It demonstrates greater anticoagulant potency in vivo compared to Warfarin. This compound has a single chiral center, resulting in two enantiomeric forms. The (R)-enantiomer has a longer plasma elimination half-life of 6.6 hours, slower plasma clearance of 1.9 L/h, and stronger anticoagulation effects than the (S)-enantiomer.

BMS-986339: oral, potent FXR agonist; binds to His298/ASN287; for PBC, PSC, NASH, anti-fibrosis research.

FXIa-IN-10 is a potent, orally bioavailable inhibitor of Activator XI (FXIa) (Ki: 0.17 nM).

Anticancer Agent 143 (Compound 369), a potent dual inhibitor targeting PTPN2 and PTP1B, exhibits IC50 values below 2.5 nM.

BLT-4 is a specific and reversible inhibitor of scavenger receptor class B type I (SR-BI). It effectively blocks the SR-BI-mediated transfer of lipids between high-density lipoprotein (HDL) and cells.

Rosiptor (AQX-1125) activates SHIP1, inhibits Akt, and reduces inflammation and allergy in rodents.

Asimicin is a effective complex I inhibitor.

7(Z),11(Z)-Nonacosadiene, a female fly pheromone, spurs male courtship; it's a C29 diene made by a female-specific elongase.

Sphingomyelin (d18:1/12:0) is a polar lipid known for its role in modulating cell signal transduction. It plays a critical role in cell membranes, influencing their fluidity and stability. Additionally, sphingomyelin (d18:1/12:0) is involved in lipid metabolism and has potential in promoting neuronal cell growth. This compound is essential for the functioning and development of the nervous system.

HSD17B13-IN-30 (compound 64) serves as a potent inhibitor of hydroxysteroid 17?-dehydrogenase 13 (HSD17B13), exhibiting an IC 50 value of less than 0.1 μM? with estradiol? as substrates. This compound is significantly implicated in the management of nonalcoholic fatty liver diseases (NAFLDs), including nonalcoholic steatohepatitis (NASH) [1].

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].

LRAT-IN-1 (compound 1) is an inhibitor of lecithin retinol acyltransferase (LRAT) with an IC50 value of 21.1 μM. This compound works by inhibiting the esterification of retinol to form retinyl esters, thereby increasing the availability of retinol in the skin to deliver anti-aging benefits. LRAT-IN-1 is under investigation for its potential use as an anti-aging ingredient in cosmetics.

Estradiol 3-glucuronide is an immunogen with antigenic properties. The antiserum induced in rabbits exhibits high affinity and specificity for Estradiol 3-glucuronide. This compound shows promise for use in research involving radioimmunoassay.

Mucidin is an antifungal antibiotic that inhibits electron transfer reactions within the mitochondrial respiratory chain's cytochrome bc1 complex.

BPU17 interacts with PHB1 and disrupts the PHB1-PHB2 interaction, causing slight mitochondrial dysfunction. This damage hinders transcription dependent on SRF/CArG-box, thereby inhibiting epithelial-mesenchymal transition (EMT) in retinal pigment epithelial cells (RPEs). BPU17 has demonstrated anti-fibrotic activity in vivo. It holds potential as a research agent for anti-angiogenic age-related macular degeneration (nAMD).

'3'-Hydroxy Repaglinide, a CYP2C8 metabolite of Repaglinide, treats type II diabetes.

Zolpyridine is a degradation product of Zolpidem tartrate.

PTP1B-IN-3 diammonium, an oral enzyme inhibitor, has potent antidiabetic and anticancer effects, with a 120 nM IC50.

HIV-1 inhibitor-40 (4ab) is a potent NNRTI (EC50: 1.9 nM), non-toxic in vivo, and a sensitive CYP inhibitor.

EGFR/VEGFR2-IN-2 (compound 4b) serves as a dual inhibitor of VEGFR-2 and EGFR.

AD013 is a selective ACE inhibitor and NEP inhibitor with potential anti-hypertensive and cardioprotective benefits.

MolPort-010-778-422 is a high-affinity inhibitor targeting the ACE2 receptor of the SARS-CoV-2 virus. It demonstrates remarkable antiviral activity with an IC50 of 8.9 nM and holds promise for use in studies related to SARS-CoV-2.

Quinapril is an orally active, non-peptide, and non-thiol angiotensin-converting enzyme (ACE) inhibitor. It primarily blocks the conversion of angiotensin I to angiotensin II in both plasma and tissues. Upon enzymatic hydrolysis, Quinapril is converted into the pharmacologically active Quinaprilat and is effective in hypertension models.

3-Benzylidenecamphor, a UV absorber, is noted for its excellent photostability and antioxidant activity. It is extensively utilized in sunscreen products to shield the skin from UV damage. Additionally, 3-Benzylidenecamphor is used in cosmetics to enhance product shelf life and safety.

PFM046 is an antagonist of the liver X receptor (LXR), effectively inhibiting the activation of LXRα and LXRβ, with IC50 values of 2.04 μM and 1.58 μM respectively. It reduces the expression of SCD1 and FASN while increasing ABCA1 expression, and demonstrates antitumor activity in mouse models.

CS-003 HCl is a TNRA - triple neurokinin receptor antagonist.

Dibutyl phosphate (DBUP) is a metabolite of organophosphate esters (OPEs) found in urine. The presence of dibutyl phosphate is positively correlated with an increased risk of sarcopenia.