Metabolism

FXR/HSD17B13 modulator 1 (compound 6) is an effective modulator of FXR/HSD17B13, playing a significant role in studies related to metabolic dysfunction-associated steatohepatitis (MASH).

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

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

Oral, brain-penetrant mutant IDH1 inhibitor targeting R132H/C with IC50: 0.021/0.045μM; 2.52μM for IDH1WT.

Arphamenine A is an inhibitor of aminopeptidase B (aminopeptidaseB) found in HMG361-CF4 of Actinomadura azurea. It exhibits inhibitory effects against Sarcoma 180 and invasive micropapillary carcinoma (IMC).

HSD17B13-IN-44 (Compound 23) functions as an inhibitor targeting hydroxysteroid 17β-dehydrogenase 13 (HSD17B13), exhibiting an IC50 value of < 0.1 μM against estradiol. This compound is applicable in the study of liver diseases or metabolic disorders [1].

D-Citrulline (H-D-Cit-OH), a stereoisomer of L-citrulline, effectively reduces cardiac contractile dysfunction caused by polymorphonuclear leukocyte (PMN) in isolated perfused rat hearts undergoing ischemia/reperfusion. This protective effect is mediated through a non-NO-mediated mechanism.

DS44470011 is an inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) with oral bioavailability. It enhances the release of erythropoietin (EPO) from cells and is utilized in research related to renal anemia.

(R,R)-BMS-986397 is a CK1α degrader with a DC50 ranging from 0.1 to 0.5 pM. This compound is applicable in leukemia research.

4-Amino-3-hydroxyphenylalanine (4-AHP) is a photodegradation product of eumelanin. It can be utilized in research focused on the formation of cutaneous melanoma and age-related macular degeneration.

Casein kinase1δ-IN-30 (Compound 581) is an inhibitor of casein kinase 1δ (CK1δ). It can be utilized in research related to neurodegenerative diseases.

Compound 142 (also known as Compound 235) is a PTPN inhibitor with potential applications in cancer research [1].

(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.

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].

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.

Propofolsulfate (sodium) is a metabolite of Propofol.

DSM705 hydrochloride: potent antimalarial, pyrrole-based DHODH inhibitor effective against Plasmodium, non-toxic to mammalian DHODH.

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].

Falecalcitriol is an analog of calcitriol. It has a higher potency both in vivo and in vitro systems, which is longer duration of action in vivo.

Nampt-IN-13 (example 58m) is an NAMPT inhibitor used in the synthesis of antibody-drug conjugates (ADCs).

JTT-553 is a DGAT1 inhibitor with an IC50 of 2.38 nM. It effectively reduces plasma levels of glucose, insulin, non-esterified fatty acids (NEFA), total cholesterol (TC), and liver triglycerides (TG). JTT-553 enhances insulin-dependent glucose absorption and glucose intolerance in the adipose tissue of diet-induced obese (DIO) mice. In KK-Ay mice, it lowers TNF-α mRNA levels and elevates GLUT4 mRNA levels in adipose tissue. By contributing to weight loss, JTT-553 improves insulin resistance in adipose tissue and overall glucose metabolism. This compound is useful for research on obesity and type 2 diabetes mellitus (T2DM).

AZ513 is a reversible FAAH inhibitor, exhibiting an IC50 of 551 nM for human FAAH and 27 nM for rat FAAH. It inhibits the hydrolysis of arachidonoyl ethanolamide in HEK293 cells transfected with human FAAH, with an IC50 of 360 nM.

DLCI-1 is a potent and selective oral inhibitor of cytochrome P450 2A6 (CYP2A6), significantly reducing self-administered nicotine doses in both male and female mice.

Buspirone N-oxide (Bu N-oxide) is a metabolite of Buspirone. Buspirone is an orally active 5-HT1A receptor agonist and a dopamine D2 (dopamine D2) autoreceptor antagonist. It is an anxiolytic agent used for research in generalized anxiety disorder.

5-Carboxy-2′-deoxycytidine is a metabolite of Trifluridine.

RBM14C12 is a compound known for its cell signaling activity. It plays a crucial role in researching lipid metabolism and cell membrane structure. Additionally, RBM14C12 can be utilized in the development of novel compounds aimed at modulating the biological mechanisms associated with lipid-related diseases.

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

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

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).

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

Deltasonamide 2 hydrochloride is a competitive high-affinity PDEδ inhibitor with a Kd of approximately 385 pM.

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

Casein kinase1δ-IN-13 (compound 401) is an inhibitor of Casein kinase1δ. It is utilized in the research of neurodegenerative diseases.

Diacylglycerolacyltransferaseinhibitor-2 (Example 8) acts as an inhibitor for diacylglycerol acyltransferase 2 (DGAT2), exhibiting an IC50 value of 3.7 nM.

NTPDase-IN-1 selectively inhibits NTPDases 1, 2, 8 with IC50 of 0.05, 0.23, 0.54 μM. Non-competitive, K m 21 μM, used in cancer, immune, infection research.

Urobilin hydrochloride, a metabolic byproduct of Hemoglobin, is excreted through urine and feces in various mammals. It also serves as an indicator of human waste contamination.

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

FR 901537 is a new aromatase inhibitor with antitumor effects.

DC371739 is an effective oral PCSK9 inhibitor that decreases both PCSK9 and ANGPTL3 mRNA expression. It also reduces PCSK9 protein expression while enhancing that of LDLR. Given its properties, DC371739 has potential applications in the study of hyperlipidemia.

MAGL-IN-15 (Compound 6), a MAGL inhibitor, holds potential for research into diseases and disorders associated with the regulation of endocannabinoid system signaling activities [1].

SHP2-IN-9: Potent SHP2 inhibitor, IC50=1.174 μM, 85x SHP1 selectivity, crosses blood-brain barrier, hampers cancer growth.

CK1δ-IN-10 (Compound 85) is an inhibitor of casein kinase 1 (CK1), specifically targeting CK1δ (CSNKID), with an IC50 value of 0.255 μM.

BAY R3401 is an orally active inhibitor of glycogen phosphorylase, leading to irreversible and non-selective inhibition of liver glycogenolysis. It suppresses glycogen breakdown in hepatocytes with IC50 values of 27.06 μM in HL-7702 cells and 52.83 μM in HepG2 cells. BAY R3401 is applicable for research in type 2 diabetes.

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

Boc 3 Arg is a tert-butyl carbamate-protected arginine compound. It serves as an efficient tag that induces degradation by directly targeting proteins to the 20S proteasome.

RORγt inhibitor 4 (Compound 9a) is an orally active RORγt inhibitor capable of penetrating the central nervous system. It has been shown to improve experimental autoimmune encephalomyelitis.

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.

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

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

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

RORγt inverse agonist 32 (compound b14) exhibits oral activity and can be utilized in inflammatory research studies.

CK1δ-IN-6 (Compound 303) is an inhibitor of Casein kinase 1δ, with potential applications in Alzheimer's disease research.

IDO antagonist-1 (compound 163), an IDO antagonist, effectively inhibits the growth of pancreatic adenocarcinoma cells in C57BL/6 mice [1].

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.

VHR-IN-1 (Compound SA1) is an effective and selective VHR phosphatase inhibitor with an IC50 of 18 nM. It hinders the proliferation of cervical cancer cells, demonstrating antitumor activity.

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].

ZSH-2208 is a retinoic acid A analogue that inhibits tumour cell proliferation and survival through RARγ-TNFAIP3 and retinoid receptors.

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

DG013A inhibits ERAP1 & ERAP2 (IC50: 33 nM & 11 nM) to research autoimmune diseases & cancer.

11β-HSD2-IN-2 (compound 3) is a selective 17β-HSD2 (17β-hydroxysteroid dehydrogenase type 2) inhibitor with an IC50 of 300 nM, studying osteoporosis.

trans-Doxercalciferol is an isomer of Doxercalciferol. Doxercalciferol is an activator of the Vitamin D receptor and prevents renal disease.

5-HT1A/5-HT7 antagonist; 5-HT1A Ki=8 nM, 5-HT7 Ki=451 nM; PDE4B IC50=80.4 μM, PDE7A IC50=151.3 μM; stronger than escitalopram.

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.

Rostratin A, a disulfide from Exserohilum rostratum, is cytotoxic to HCT-116 cells with an IC50 of 8.5 μg/mL.

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

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

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

PDE1-IN-7 (Compound 13h), with an IC50 value of 10 nM, selectively inhibits bPDE1. This compound demonstrates significant anti-fibrotic effects in a BDL-induced liver fibrosis rat model and is useful for research purposes in studying liver fibrosis [1].

The compound 3,3'-[Dithiobis[2,1-ethanediyl(methylimino)]]bis[1-propanol] is an SS-cleavable, proton-activated lipid-like substance (SSPalm) that facilitates the delivery of plasmid DNA.

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

JTZ-951 is a potent and orally active inhibitor of hypoxia inducible factor prolyl hydroxylase (PHD).

CA IX-IN-1 (compound 12g) is a potent and highly selective hCA IX inhibitor (IC50: 7 nM) that exhibits antitumour effects.

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

Retezorogant is a retinoic acid receptor-related orphan receptor gamma (RORγ) antagonist.

Mosapride N-Oxide, a major active metabolite of Mosapride, is a gastroprokinetic agent that acts as a selective 5HT4 agonist.

BAR-2227 (compound 3a) functions as an FXR agonist and a LIFR inhibitor. It is utilized in the study of liver fibrosis and inflammation.

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

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.

BAY-179 is a potent, selective, species cross-reactive complex I inhibitor for the study of cancer.

α-Glucosidase-IN-13 is an inhibitor of α-glucosidase (IC50: 5.69 μM).

HIF-1α-IN-4 is an inhibitor of HIF-1α with IC50 of 24 nM in HEK293T cells which has potential antitumor effects.

APOL1-IN-3 is an APOL1 inhibitor used for kidney disease research.

PTP1B-IN-21 inhibits PTP1B (IC50=1.56μM) selectively over TCPTP, a type 2 diabetes target.

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

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

Magnesium ionophore III (ETH 4030) is an ion carrier that regulates intracellular magnesium ion concentrations. It enhances cellular functions and metabolic activities by increasing the permeability of cell membranes to magnesium ions. Additionally, Magnesium ionophore III is utilized in research to explore the significance of magnesium ions in biological processes and their impact on cellular physiology.

Lipid HTO12 is an ionizable lipid used for forming lipid nanoparticles (LNP). It facilitates the delivery of siRNA and mRNA.

(±)-HIP-B is an excitatory amino acid transporter blocker.

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.

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

DOCP (2-((2,3-Bis(oleoyloxy)propyl)dimethylammonio)ethyl hydrogen phosphate) is a lipid characterized by an opposite charge orientation compared to traditional phosphatidylcholine (PC) lipids, featuring quaternary ammonium near the bilayer interface and phosphate groups projecting into the aqueous environment. This unique structure of iPC lipids presents an excellent opportunity to investigate the biophysical characteristics and biological activities influenced by the reversal of surface charges on bilayers.

Potent hCA inhibitor: targets hCA II, IX & XII with IC50s of 42.9, 47.6, & 6.7 nM respectively.

P053: potent, selective CerS1 inhibitor, IC50 = 0.5µM, curbs muscle fat oxidation, affects body fat.

NAZ2329: Cell-permeable, targets R5 RPTPs, inhibits hPTPRZ1 (IC50=7.5 μM) & hPTPRG (IC50=4.8 μM), hampers glioblastoma growth, affects stem cell traits.

L-690330 hydrate inhibits IMPase; Ki: 0.30 μM (human), 0.42 μM (bovine cortex); 0.27 μM (recom. human), 0.19 μM (bovine).

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

6′SLN is a characteristic glycan found on the surface of cancer-related extracellular vesicles (EVs) and serves as the primary form of protein glycosylation within EVs. Additionally, 6′SLN, a derivative of sialic acid, interacts with hemagglutinins (HAs) from both human and avian influenza strains, making it relevant in the study of anti-influenza drugs.

Darlifarnib (Compound (S)-058) is an inhibitor of farnesyl transferase and geranylgeranyltransferase, with IC50 values of ≤ 10 nM and > 1000 nM, respectively. It exhibits high metabolic stability in human and mouse liver microsomes, with a half-life of over 100 minutes.