Metabolism

<p>ZK168281 is a 1α,25(OH)2D3 analog, VDR antagonist with 0.1 nM Kd, and blocks receptor CoA interaction.</p>

<p>ENPP1-IN-12 is a potent, oral ENPP1 inhibitor with a Ki of 41 nM and anti-tumor properties.</p>

<p>HIF-2α-IN-5 is a potent HIF-2α inhibitor with an IC 50 of &lt; 50 nM [1].</p>

<p>AZD 4407 is a potent inhibitor of 5-lipoxygenase.</p>

<p>T-3764518 is a novel and potent inhibitor of stearoyl coenzyme A desaturase (SCD)(IC50 of 4.7 nM).</p>

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

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

<p>GK420 (AVX420) is a potent inhibitor of cytoplasmic phospholipase A2α (cPLA2α), with an XI(50) value of 0.0016. It effectively inhibits the release of arachidonic acid, with an EC50 of 0.09 μM. GK420 plays a significant role in cancer research.</p>

<p>Implitapide is an inhibitor of microsomal triglyceride transfer protein (MTP).</p>

<p>EtoricoxibN1'-oxide is a metabolite of Etoricoxib. It does not inhibit COX-1 and does not significantly inhibit COX-2.</p>

<p>ZK159222 is an effective 1α,25-(OH)2D3 receptor (VDR) agonist. ZK159222 has a partial agonistic character.</p>

<p>FXR agonist12 (Compound C7) is an orally active FXR agonist. It downregulates bile acid synthesis-related genes and upregulates bile acid transport-related genes in HepG2 cells. FXR agonist12 alleviates ANIT-induced cholestasis and reduces liver damage and fibrosis in a mouse model of NASH.</p>

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

<p>Lecufexor is an agonist of the farnesoid X receptor (FXR).</p>

<p>Lapaquistat: active TAK-475 metabolite; reduces cholesterol synthesis and statin myotoxicity.</p>

<p>Fonadelpar is an agonist of PPARδ. It also is used in the research of neuroparalytic keratopathy.</p>

<p>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.</p>

<p>BMS-185354 is a selective RARγ activator with an EC50 value of 28 nM, offering potential for cancer research.</p>

<p>Propofolsulfate (sodium) is a metabolite of Propofol.</p>

<p>Homodestcardin: cyclic depsipeptide from T. roseum with immunosuppressant properties; inhibits mouse T cell proliferation.</p>

<p>DPM-1003 is an allosteric inhibitor of PTP1B, targeting the non-catalytic, disordered C-terminal segment of the PTP1B protein, and has shown beneficial effects in reducing pulmonary inflammation in mice.</p>

<p>Compound 13, identified as h15-LOX-2 inhibitor 3, exhibits inhibitory activity against h15-LOX, with IC50 and Ki values of 25 μM and 15.1 μM, respectively.</p>

<p>FTI-2148 blocks RAS-related FT-1 &amp; GGT-1; IC50: 1.4 nM &amp; 1.7 μM.</p>

<p>LDHA-IN-5 is a novel and potent inhibitor targeting both glycolate oxidase (GO) and lactate dehydrogenase A (LDHA), designed for the treatment of primary</p>

<p>BT-114143 is a plasminogen activator inhibitor with an IC50 of 8.42 μM. It is applicable in research related to hemorrhagic diseases caused by excessive fibrinolysis, including traumatic bleeding, severe menorrhagia, postpartum hemorrhage, and complications of hemophilia.</p>

<p>Glucokinase activator7 is an activator of glucose kinase (Glucokinase) and can be utilized in research on diabetes and hyperglycemia [refer to compound on page 176].</p>

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

<p>Cilazaprilat is the active metabolite of cilazapril, a pyridazine angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity.</p>

<p>CK1δ-IN-8 (Compound 429) is a CK1δ inhibitor suitable for Alzheimer's disease research.</p>

<p>(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.</p>

<p>GW461484A is a small molecule inhibitor targeting Candida albicans Yck2, exhibiting an IC50 of 0.11 µM. It has a MIC80 of 12.5 µM against C. albicans. GW461484A shows potential for research into fungal diseases, including drug-resistant Candida infections.</p>

<p>Casein kinase1δ-IN-26 (compound 505) is a potent inhibitor of casein kinase 1δ. This compound is applicable in research related to neurodegenerative disorders such as Alzheimer’s disease.</p>

<p>SMase-IN-1 (Compound 4) is a bacterial sphingomyelinase (SMase) inhibitor with an IC50 value of 6.43 µM against Bacillus cereus SMase. It also inhibits eqBuChE with an inhibition rate of 59.50% at a concentration of 50 µM. SMase-IN-1 forms a complex with Cu2+ through bio-metal interactions and can inhibit hemolysis of sheep red blood cells induced by Bacillus cereus.</p>

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

<p>L 691816 is an effective inhibitor of the 5-LO reaction.</p>

<p>TNP-470 is a methionine aminopeptidase-2 inhibitor. TNP-470 is also an angiogenesis inhibitor.</p>

<p>NR1H4 activator 1 is a potent and selective agonist of Famesoid X Receptor (FXR).</p>

<p>(2S,4S)-Sacubitril (Sacubitril Impurity C) is a stereoisomer derived from Sacubitril which is a potent NEP inhibitor.</p>

<p>5-HT1A antagonist; Ki=8nM, Kb=0.04nM. PDE4B IC50=80.4μM; PDE7A IC50=151.3μM. Good biofilm penetration, stable, anticognitive, antidepressant.</p>

<p>LXRβ agonist-2 is a highly potent and β-selective liver X receptor (LXRβ) agonist with EC50 of 7 nM.</p>

<p>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.</p>

<p>PTP1B-IN-17, a benzimidazole derivative, inhibits PTP1B (Ki: 30.2 μM) and may help study type 2 diabetes.</p>

<p>ATX inhibitor 22 is a novel inhibitor of ATX (autotaxin) (IC50: 218.9 μM) that lacks inhibitory activity against LPAR1.</p>

<p>AChE/hCA I-IN-1 (Compound L3) is an inhibitor of acetylcholinesterase (AChE) and carbonic anhydrase (CA), effectively inhibiting AChE, hCA I, and hCA II with IC50 values of 302 nM, 265 nM, and 283 nM, respectively.</p>

<p>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.</p>

<p>Mutant IDH1-IN-3 (Compound 1) is a selective allosteric inhibitor targeting the mutant isocitrate dehydrogenase 1 (IDH1), with an IC50 of 13 nM for R132HIDH1. It effectively suppresses the production of D-2-hydroxyglutarate (2HG) in cells and is applicable for research in oncology.</p>

<p>5-Carboxy-2′-deoxycytidine is a metabolite of Trifluridine.</p>

<p>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.</p>

<p>Benfooxythiamine is a transketolase (TKT) inhibitor that suppresses SARS-CoV-2 replication and enhances the activity of the glycolysis inhibitor 2DG. It exhibits antiviral properties.</p>

<p>LEQ803 (N-DesmethylRibociclib) is a metabolite of the CDK4/6 inhibitor Ribociclib, produced through metabolism by CYP3A4. This compound holds potential applications in the field of oncology.</p>

<p>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.</p>

<p>4-MDM (4-Methoxydiphenylmethane) is an orally active anti-inflammatory compound that selectively enhances the aminopeptidase activity of leukotriene A4 hydrolase (LTA4H). By promoting the degradation of proline-glycine-proline by LTA4H, 4-MDM reduces neutrophil recruitment in the lungs, alleviating inflammation without affecting the epoxide hydrolase activity of LTA4H. This compound is useful for research in pulmonary diseases.</p>

<p>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).</p>

<p>CA inhibitor 4, photoprobe; targets hCA I-XIV; Ki: 640-1166 nM.</p>

<p>PDHK-IN-5, potent PDHK2 (0.006 μM IC50) &amp; PDHK4 (0.0329 μM IC50) inhibitor, may be explored for cancer and diabetes treatment.</p>

<p>Miaosporone A: angucyclic quinone, cytotoxic to MCF-7, NCI-H187, Vero cells; anti-TB and anti-malaria with IC50 of 2.4 μM, 2.5 μM.</p>

<p>Raloxifene N-Oxide is a Raloxifene oxidative degradation product.</p>

<p>Pyripyropene A is a potent and selective inhibitor of sterol O-acyltransferase 2 (SOAT2)/acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2)(IC50 of 0.07 μM).</p>

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

<p>Lp(a)-IN-7 (example 1) is an inhibitor of lipoprotein (a) [Lp(a)] formation, exhibiting an IC50 of 2.51 nM in media containing apolipoprotein B (apoB) and apolipoprotein (a). This compound is applicable in cardiovascular disease research.</p>

<p>SHP2 IN-1 is an allergic SHP2 (PTPN11) inhibitor(IC50 : 3 nM).</p>

<p>Desmonomethylpromazine is a demethylated metabolite of Promazine that can penetrate the brain. It enters red blood cells and tissues via passive diffusion and is distributed in organs such as the lungs, liver, and kidneys in rats.</p>

<p>Beloranib is a fumagillin anticancer drug. Beloranib belongs to an angiogenesis inhibitor.</p>

<p>RORγt inverse agonist 34 (compound 5a) is an inverse agonist for RORγt, exhibiting an IC50 of 0.094 μM for the inhibition of RORγt-LBD. This compound is utilized in psoriasis research.</p>

<p>Oral ATX inhibitor 12 (IC50: 1.72 nM) at 60 mg/kg prevents lung damage in C57Bl/6J mice.</p>

<p>HIF-1α-IN-5 is an inhibitor of HIF-1α with an IC 50 value of 24 nM in HEK293T cells that also inhibits the activity of MAO-A.</p>

<p>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.</p>

<p>Carbonic anhydrase inhibitor 3 (compound 11g) is an inhibitor of carbonic anhydrase II that reduces the intraocular pressure in glaucomatous rabbits [1].</p>

<p>GSK2945 HCl is a specific Rev-erbα antagonist, EC50: 21.5 μM (mouse), 20.8 μM (human), increases cholesterol 7α-hydroxylase.</p>

<p>NAMPT activator-6, a regulatory molecule for the optical control system of NAMPT and NAD+, can be used to design efficient photoswitchable proteolysis-targeting chimeras (PS-PROTACs) for light-dependent, reversible regulation of NAMPT and NAD+, thereby reducing toxicity associated with inhibitor-based PS-PROTACs. This enables antitumor activity and in vivo modulation of NAMPT and NAD+ through optical manipulation [1].</p>

<p>Phospho-L-arginine is a derivative of arginine.</p>

<p>SDX-7539 is a selective MetAP2 inhibitor that inhibits the proliferation of HUVEC, with an IC50 of 120 μM. It has demonstrated antitumor activity in xenografted NSCLC in athymic nude mice.</p>

<p>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].</p>

<p>RORγt/DHODH-IN-3 (compound (S)-14d) is a potent, orally active dual inhibitor of RORγt (IC50: 0.098 μM) and DHODH (IC50: 0.432 μM).RORγt/DHODH-IN-1 has</p>

<p>Casein kinase1δ-IN-18 (compound 660) is an inhibitor of casein kinase 1δ (CK1δ), which can be utilized for research in neurodegenerative diseases.</p>

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

<p>Alkannin: potent, tumor-specific PKM2 inhibitor; non-inhibitory to PKM1/PKL; potential anticancer agent.</p>

<p>Porphobilinogen act as a phytotoxin, a metabotoxin, and a neurotoxin.</p>

<p>TS010 is a highly potent inhibitor of GLO-I, with an IC50 value of 0.57 μM. It holds significant promise for advancements in cancer research [1].</p>

<p>DEL-I25 is an effective activator of GPX4 that protects cells from ferroptosis (iron-dependent cell death).</p>

<p>RMGPa-IN-1 (Compound 10C) is an inhibitor of rabbit muscle glycogen phosphorylase a (RMGPa), exhibiting an IC50 value of 82.5 μM. This compound holds potential for research in diabetes.</p>

<p>GGACK (H-Glu-Gly-Arg-CMK) is an irreversible substrate-like inhibitor of the serine protease urokinase-type plasminogen activator (uPA).</p>

<p>FABP1-IN-1 (44) is a selective FABP1 inhibitor with an IC50 value of 4.46 μM. It is applicable in research related to alcoholic fatty liver disease.</p>

<p>ROR1-IN-1 (Compound 19h) is an inhibitor of receptor tyrosine kinase-like orphan receptor 1 (ROR1) with a Ki of 0.10 μM. It inhibits the proliferation of cancer cell lines H1975, A549, and MDA-MB-231, with IC50 values of 0.36 μM, 1.37 μM, and 0.47 μM, respectively. In mice, ROR1-IN-1 demonstrates antitumor efficacy and exhibits favorable pharmacokinetic properties in a rat model.</p>

<p>α-Glucosidase-IN-17 (Compound 12B) is a potent and orally active inhibitor of α-glucosidase, demonstrating antidiabetic activity with an inhibitory</p>

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

<p>Bestatin methyl ester (600, 900 µM; 24 h) inhibits spore cell differentiation in Dictyostelium discoideum.</p>

<p>CGS-24592 is an orally active, selective, and potent inhibitor of neutral endopeptidase 24.11 (NEP), with an IC50 value of 1.6 nmol/L. It reduces the degradation of atrial natriuretic peptide (ANP), thereby increasing plasma ANP concentration and lowering blood pressure. CGS-24592 shows potential for research in cardiovascular diseases such as hypertension and congestive heart failure.</p>

<p>LTA4H-IN-2 (compound (S)-2) acts as an orally active inhibitor targeting Leukotriene A4 Hydrolase, exhibiting potent activity with an IC 50 of less than 3 nM [1].</p>

<p>Epoxykynin is a potent soluble epoxide hydrolase (sEH) inhibitor [1].</p>

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

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

<p>HIF-1/2α-IN-1, an orally active compound, functions as an inhibitor of HIF-2α.</p>

<p>EAAT2(GLT1)-selective non-transportable inhibitor of L-glutamate and L-aspartate uptake</p>

<p>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].</p>

<p>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.</p>

<p>ZK824859 hydrochloride: oral uPA inhibitor with IC50 of 79 nM (uPA), 1580 nM (tPA), 1330 nM (fibrin).</p>

<p>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].</p>

<p>ABHD antagonist 1 is an inhibitor of ABHD6 (α/β-Hydrolase domain containing 6), involved in modulating biochemical pathways affected by ABHD6, thereby influencing cell function and inflammatory responses. This compound is applicable for research in fields such as pain, neurological disorders, inflammatory diseases, autoimmune diseases, metabolic disorders, and cancer.</p>

<p>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.</p>