Metabolism

<p>Raloxifene Bismethyl Ether hydrochloride is a Raloxifene metabolite and an estrogen receptor inactive compound on which both hydroxyl groups are absent.</p>

<p>15-PGDH-IN-1: potent oral 15-PGDH inhibitor, IC50=3nM, useful for tissue repair research.</p>

<p>5-Lipoxygenase-In-1 (compound example 4.10) is a 5-Lipoxygenase inhibitor.</p>

<p>γ-CEHC, a metabolite of γ-tocopherol, is predominantly excreted through urine, primarily in its conjugated form as glucuronide [1], rather than through bile.</p>

<p>C12-113, a lipidoid delivery agent, effectively transfects siRNA into cells and, when combined with additional lipids, forms lipid nanoparticles (LNPs). These LNPs facilitate the delivery of mRNA encoding the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in mice [1] [2].</p>

<p>PXS-6302 hydrochloride is a potent irreversible lysine oxidase (LOX) inhibitor, inhibiting Bovine LOX, rh LOXL1, rh LOXL2, rh LOXL3, and rh LOXL4 with IC50 of 3</p>

<p>NPAS3-IN-1 is an NPAS3-ARNT heterodimerization inhibitor that regulates NPAS3 transcription by modulating the heterodimerization of NPAS3 with ARNT.</p>

<p>WAY-620147 inhibits Monoamine Oxidase and can be used for the study of neurological disorders.</p>

<p>BI-3231 is a hydroxysteroid 17ß-dehydrogenase 13 HSD17B13 inhibitor that inhibits hHSD17B13 .BI-3231 can be used to study cirrhosis.</p>

<p>NEP-IN-1 is an inhibitor of neutral endopeptidase (NEP, IC50 = 2 nM) and can be used in studies about female sexual arousal disorders.</p>

<p>p-Ethynylphenylalanine (4-Ethynyl-L-phenylalanine), a tryptophan hydroxylase (TPH) inhibitor, is competitive, effective, selective, and reversible, with a Ki of</p>

<p>WAY-297848 is a novel glucokinase activator for the prevention or treatment of hyperglycemia, diabetes mellitus, obesity, dyslipidemia, and metabolic syndrome.</p>

<p>KB-74935: enzyme inhibitor, mineralocorticoid blocker, treats cholesterol, hypolipidemia, neurological issues, Alzheimer's.</p>

<p>Fluspirilene is a long-acting antipsychotic for schizophrenia, inhibiting L-type calcium channels (IC50: 0.03 μM).</p>

<p>Mitiperstat, a strong MPO inhibitor, helps prevent heart failure and coronary artery disease.</p>

<p>Calcium channel-modulator-1 is a calcium channel-modulator (IC50:0.8 μM) with specialisation to block aortic constriction.</p>

<p>TP-10 is a selective inhibitor of PDE10A against other PDEs with IC50 of 0.8 nM.</p>

<p>h-NTPDase-IN-2 is a broad-spectrum NTPDase inhibitor that inhibits multiple h-NTPDas isoforms.</p>

<p>Inolitazone (RS5444) a high-affinity PPARγ agonist. Inolitazone exhibits IC50 for growth inhibition is ~0.8 nM in vitro.</p>

<p>CB29 is a specific inhibitor of aldehyde dehydrogenase 3A1 (ALDH3A1).</p>

<p>Cudetaxestat (BLD-0409) is a potent inhibitor of orally active autotaxin.</p>

<p>Varespladib methyl (LY333013), a bioavailable prodrug of Varespladib, is a selective group II secretory phospholipase A2 inhibitor.</p>

<p>Ranirestat (AS-3201) is an AR inhibitor with neuroprotective properties that improves peripheral nerve dysfunction in rats with advanced diabetic polyneuropathy</p>

<p>ALDH2 modulator 1 is a potent and orally active modulator of acetaldehyde dehydrogenase-2 (ALDH2), which reduces blood alcohol levels in mice.</p>

<p>4A3-SC8 is a modular, degradable dendrimer facilitating the extension of survival in aggressive liver cancer models through the delivery of small RNAs [1].</p>

<p>Dechloro Rivaroxaban is a Factor Xa inhibitor that inhibits free FXa and plasminogen and fibrin-associated FXa activity in humans.</p>

<p>CCT365623: oral Lysyl Oxidase inhibitor, potent, selective, good pharmacokinetics, anti-metastatic.</p>

<p>PDE9-IN-(S)-C33: potent PDE9 inhibitor with 11 nM IC50, for CNS diseases and diabetes study.</p>

<p>Rilapladib (SB 659032) is a selective inhibitor of Lipoprotein-Associated Phospholipase A2(Lp-PLA2, IC50 = 230 pM) and an antagonist of the platelet activating</p>

<p>HIF-2α agonist 2 is an HIF-2α agonist with an EC50 value of 1.68 μM for HIF-2α.</p>

<p>TPN171 is potent PDE5 inhibitor with subnanomolar potency for PDE5 and good selectivity over PDE6, which has the potential for the treatment of pulmonary</p>

<p>7-BIA is a receptor-type protein tyrosine phosphatase D (PTPRD) inhibitor with anti-addictive properties and can be used in the study of neuropathic pain.</p>

<p>ER-50891 is a potent RARα antagonist, countering retinoic acid inhibition and aiding BMP2-induced osteoblast differentiation.</p>

<p>Cis-22a: selective TRPV6 inhibitor (IC50=0.32μM), halts T47D breast cancer cell growth.</p>

<p>Ecopladib inhibits cPLA2α with IC50 of 0.15 μM (micelles) &amp; 0.11 μM (rat blood).</p>

<p>DGAT-1 inhibitor 2: effective against obesity, targets enzyme in triglyceride synthesis for diabetes treatment.</p>

<p>Xanthine oxidase-IN-1 is an effective inhibitor of xanthine oxidase with an IC50 value of 6.5 nM.</p>

<p>Enpp-1-IN-16 is an ENPP1 inhibitor, yo anti-cancer activity.Enpp-1-IN-16 can be used to study insulin resistance and chondrocalcinosis.</p>

<p>ML400 (CID73050863) is an allosteric inhibitor of LMPTP with an EC50 of 1μM. ML400 displays good cell-based activity and rodent pharmacokinetics.</p>

<p>AMG 579 is an efficacious and selective inhibitor of PDE10A (IC50 = 0.1 nM).</p>

<p>PA452 is a selective antagonist of retinoic X receptor (RXR) and suppresses the effect of Retinoic acid on Th1/Th2 development.</p>

<p>RS 8359 is a selective MAO-A reversible inhibitor with a 2200:1 A:B ratio, exhibiting antidepressant effects.</p>

<p>OGT 2115 blocks heparanase (IC50=0.4µM), cleaving heparan sulfate; antiangiogenic (IC50=1µM).</p>

<p>Setileuton (MK0633) is a specific 5-LOX inhibitor and can be used in research on asthma and atherosclerosis.</p>

<p>Mutant IDH1-IN-2 is a inhibitor of mutant Isocitrate dehydrogenase (IDH) proteins, with IC50 of 16.6 nM in Fluorescence biochemical assay, IC50 of ＜22 nM in LS-</p>

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

<p>MAGL-IN-20 (compound ±34) is a reversible inhibitor of monoacylglycerol lipase (MAGL). It exhibits significant antiproliferative activity against a range of cancer cell lines, including H460, HT29, CT-26, Huh7, and HCCLM-3.</p>

<p>FXR agonist9 (compound 26) is a selective, orally active partial agonist of FXR with an EC50 of 0.09 µM (maximum efficacy of 75.13%). It ameliorates the pathological features of fatty liver disease in mice induced by HFD and CCl4-related metabolic dysfunction.</p>

<p>FXIa-IN-8: potent FXIa blocker (IC50: 14.2 nM), anti-thrombotic, low bleeding/toxicity risk.</p>

<p>7PPD-Q is a substituted p-phenylenediamine antioxidant derivative. It exhibits toxicity towards the bacterium V. fischeri (EC50= 14.9 mg/L).</p>

<p>PKR-IN-1 (Compound 5s) is a pyruvate kinase (PK) inhibitor with antifungal properties, exhibiting an EC50 of 0.21 μg/mL against Rhizoctonia solani (R. solani).</p>

<p>RWJ 22108 is a bronchial-selective calcium channel (calcium channel) blocker that exhibits an IC50 of 5.7 nM in dog bronchial smooth muscle calcium-dependent contractions.</p>

<p>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.</p>

<p>PDHK-IN-3 (compound 7) is a potent inhibitor of pyruvate dehydrogenase kinase(PDHK) with IC50s of 0.21 and 1.54 μM for PDHK2 and PDHK4, respectively [1].</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>Lp(a)-IN-5 (Compound A) is an orally active inhibitor of lipoprotein (a) [Lp(a)]. It effectively inhibits the assembly of Apo(a) and ApoB proteins, with an IC50 value of 0.41 nM. Lp(a)-IN-5 shows potential for research into diseases associated with elevated plasma Lp(a) levels, such as cardiovascular diseases.</p>

<p>SelB-1 acts as a dual inhibitor of Topoisomerase I/II (TopoisomeraseI/II), exhibiting anticancer activity suitable for research on prostate and colon cancers. Additionally, SelB-1 can induce the expression of autophagy (autophagy) genes and lipid peroxidation while reducing GSH levels.</p>

<p>(S)-CPP sodium serves as an inhibitor of the branched-chain α-keto acid dehydrogenase complex (BCKDC) kinase, commonly referred to as BDK or keto acid dehydrogenase kinase. As a negative regulator of BCKDC activity, (S)-CPP (IC50 of 6.3 μM) inhibits BDK, which activates the complex, leading to a significant reduction in the levels of leucine/isoleucine and valine in the plasma of wild-type 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>Ro 23-9358 is a potent inhibitor of secretory phospholipase A2, exhibiting anti-inflammatory properties.</p>

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

<p>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.</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>MRS4458 is an effective inhibitor of the P2Y14 Receptor.</p>

<p>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.</p>

<p>PDE4B-IN-3 is a potent inhibitor of PDE4B (IC50: 0.94 μM) and exhibits anti-inflammatory effects.</p>

<p>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.</p>

<p>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).</p>

<p>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.</p>

<p>PTP1B-IN-18 is an orally active, fully mixed protein tyrosine phosphatase 1B (PTP1B) inhibitor (Ki: 35.2 μM).PTP1B-IN-18 can be used to study type 2 diabetes.</p>

<p>4-Acetylphenylboronic acid acts as an effective inhibitor targeting carbonic anhydrase II (CAII), displaying inhibitory concentrations (IC50) of 246 μM for bovine CAII (bCA II) and 281.40 μM for human CAII (hCA II).</p>

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

<p>AChE/BChE-IN-23 (Compound 6e) is a dual inhibitor of acetylcholinesterase and butyrylcholinesterase, exhibiting IC50 values of 0.91 μM for AChE, 1.19 μM for eqBChE, and 1.01 μM for hBChE. This compound also demonstrates antioxidant properties and inhibits the aggregation of Aβ1-42 and Tau proteins. Moreover, AChE/BChE-IN-23 prevents the activation of microglial cells by inhibiting the release of reactive oxygen species and mitochondrial damage. Additionally, it reduces the levels of the NLRP3 inflammasome in human microglial cells and reverses memory impairment in mice induced by scopolamine.</p>

<p>TAP311 is an inhibitor of cholesteryl ester transfer protein (CETP)(IC50 of 62 nM).</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>Fonadelpar is an agonist of PPARδ. It also is used in the research of neuroparalytic keratopathy.</p>

<p>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.</p>

<p>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).</p>

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

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

<p>PNPLA3 Modifier 1 (Compound 10), a modifier of patatin-like phospholipase domain-containing protein 3 (pnpla3), exhibits a geometric mean EC50 of 4.9 nM.</p>

<p>Slow isomerization of the C-11 double bond of LTE4 leads to the formation of 11-trans LTE4. 11-trans LTE4 is equipotent to LTE4 in contracting guinea pig ileum.</p>

<p>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.</p>

<p>(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.</p>

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

<p>(+)-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.</p>

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

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

<p>20-HEDE (WIT 002) is a 20-hydroxyeicosatetraenoic acid (20-HETE) antagonist.</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>L 668411, the 2,3-ditritiated methyl ester of L 659699, inhibits HMG-CoA synthase.</p>

<p>CK2-IN-3: potent, selective CK2 inhibitor; Kd=12 nM, IC50: 1.51 μM (CK2α), 7.64 μM (CK2α'). For cancer research.</p>

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

<p>Mibefradil is a calcium channel blocker with moderate selectivity for T-type Ca2+ channels (IC50s: 2.7 μM and 18.6 μM for T-type and L-type currents).</p>

<p>m-APTA (5'-S-(3-aminophenyl)-5'-thioadenosine) is a selective chemoprotective agent targeting methylthioadenosine phosphorylase (MTAP). It can be converted into adenine, which is a crucial step in shielding normal cells from the toxicity of nucleobase analogs (NBA). m-APTA holds potential for research in MTAP-deficient cancers.</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>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>Carbonic anhydrase inhibitor19 (compound 26a) targets glaucoma-associated isozymes hCA II and hCA XII, with inhibition constants (Kis) of 9.4 nM and 6.7 nM, respectively. This compound is effective in reducing intraocular pressure.</p>

<p>α-Glucosidase-IN-43 (compound AS14) is an α-glucosidase inhibitor with an IC50 of 4.32 μM, demonstrating acute blood-glucose-lowering properties. It is safe and effective in vivo, showing no toxicity to normal fibroblasts in mice and can ameliorate diabetes induced by streptozotocin in rats. α-Glucosidase-IN-43 is applicable for research on postprandial hyperglycemia in diabetic patients.</p>

<p>PRL3-CNNM4 interaction-IN-1 (Compound C28d52) is an inhibitor of the PRL3-CNNM4 interaction that also suppresses CNNM inhibition mediated by PRL. This compound exhibits favorable pharmacokinetic and drug metabolism properties.</p>