Metabolism

<p>FAAH/MAGL-IN-2: potent, reversible, oral FAAH &amp; MAGL inhibitor, IC50: 11/36 nM, may research neuropathic pain, no locomotion issue.</p>

<p>L-Sepiapterin aids in making BH4, a coenzyme essential for eNOS, enhancing artery function and angiogenesis, while suppressing ovarian cancer cell growth.</p>

<p>Mitapivat (AG-348) hydrochloride is an orally active and selective allosteric activator of pyruvate kinase R (PK-R). It enhances the PK-R-catalyzed conversion of phosphoenolpyruvate to pyruvate, thereby promoting the glycolysis pathway, increasing ATP production in red blood cells, and decreasing 2,3-diphosphoglycerate (2,3-DPG) levels. Mitapivat hydrochloride is being investigated for potential use in the study of pyruvate kinase deficiency and other anemia-related disorders.</p>

<p>Yck2-IN-1 (Compound 2a) is an inhibitor of the fungus Candida albicans Yck2. It has an IC50 of approximately 80 nM for Yck2 and an MIC80 of 12.5 µM for C. albicans, demonstrating good metabolic stability [66% remaining in mouse liver microsomes]. In a mouse model with drug-resistant Candida, Yck2-IN-1 significantly reduced fungal load in the kidneys. Yck2-IN-1 shows potential for research in antifungal infection treatments.</p>

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

<p>AD011, a cACE/NEP inhibitor derived from lenopril-tryptophan, may offer strong anti-hypertensive, cardioprotective benefits.</p>

<p>PPI-2458, a fumagillin derivative, irreversibly blocks MetAP2, hindering abnormal cell growth and angiogenesis with improved toxicity.</p>

<p>Casein kinase1δ-IN-17 (compound 753) is an inhibitor of casein kinase 1δ (CK1δ). It is applicable in research related to neurodegenerative diseases.</p>

<p>α-Glucosidase-IN-12 is a potent inhibitor of α-glucosidase (IC50: 10.20 μM).</p>

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

<p>Compound 11, a selective PPARδ agonist, demonstrates an EC50 of 20 nM, indicating its high affinity for PPARδ receptors. This compound efficiently reduces levels of nitric oxide (NO), as well as the pro-inflammatory cytokines TNFα and IL-6 in LPS-stimulated RAW264.7 cells via the NF-κB pathway, showcasing its anti-inflammatory properties. Additionally, Compound 11 exhibits remarkable stability in human liver microsomes and plasma. It significantly ameliorates foot edema induced by Carrageenan, displaying favorable pharmacokinetic properties with a bioavailability of approximately 100%.</p>

<p>BAY 74-4113 is a DGAT1 inhibitor with an IC50 of 72 nM. It is utilized in research related to obesity.</p>

<p>CYP121A1-IN-1: Strong inhibitor for CYP121A1, hinders Mycobacterium tuberculosis growth (MIC 90 ~6.25 μM), reduces mycocyclosin synthesis.</p>

<p>EB-0176: A valerian derivative; broad-spectrum antiviral; potent ER α-glucosidase I/II inhibitor; IC50s: 0.6439/0.0011 μM.</p>

<p>hCAII-IN-5 (compound 12h) is a potent, selective inhibitor of human carbonic anhydrase II (hCA II) with an inhibition constant (IC50) of 4.55 µM [1].</p>

<p>IDO2-IN-1: potent oral IDO2 inhibitor, IC50 = 112 nM, for inflammatory autoimmunity research.</p>

<p>Rostratin B, a cytotoxic disulfide, demonstrates in vitro cytotoxicity against human colon carcinoma (HCT-116), exhibiting an IC50 value of 1.9 μg/mL.</p>

<p>ASB14780 is a 4-phenoxy derivative and an inhibitor of cytoplasmic phospholipase cPLA2α (IC50: 20 nM).</p>

<p>RORγt/DHODH-IN-1 (compound (R)-14d) is a potent, orally active dual inhibitor of RORγt (IC50: 0.083 μM) and DHODH (IC50: 0.172 μM), which exhibits significant</p>

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

<p>OSI-413 (free base) (CP 373413) is the primary metabolite of Erlotinib. Erlotinib (CP-358774) acts as a direct EGFR tyrosine kinase inhibitor with an IC50 of 2 nM against human EGFR.</p>

<p>Indoluidin E selectively inhibits DHODH and has an inhibitory effect on cancer cell growth.</p>

<p>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).</p>

<p>Compound B15: potent sEH inhibitor (0.03 nm), reduces inflammation &amp; pain.</p>

<p>PHGDH-IN-2: potent PHGDH inhibitor, IC50=5.2μM; hinders PHGDH cancer cell growth &amp; serine synthesis in MDA-MB-468.</p>

<p>Ketomethylenebestatin, a weaker carba-analog of aminopeptidase inhibitor bestatin, is 10x less potent.</p>

<p>Oxoprolintane is a metabolite of the psychoactive compound Prolintane. It exhibits activity in modulating the central nervous system and may serve as a potential neuroprotective agent. Oxoprolintane shows promise for research in the field of neurological disorders.</p>

<p>BAY 3389934 is a dual inhibitor of factor IIa (factor IIa) and factor Xa (factor Xa), providing anticoagulant and organ-protective effects. It alleviates coagulopathy and organ dysfunction in baboon models of Staphylococcus aureus sepsis.</p>

<p>orally active ghrelin receptor (GHS-R1a) agonist</p>

<p>SEH inhibitor-2 is an orally active sEH blocker (IC50=0.9 nM) with predicted 71.2-88.4% absorption, potentially aiding cardiovascular health.</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>PDHK-IN-4 inhibits PDHK2 (IC50: 0.0051 μM) &amp; PDHK4 (IC50: 0.0122 μM), with potential for cancer research.</p>

<p>RORγt Inhibitor 2, a potent inhibitor of RORγt, exhibits an IC50 of 9.2 nM and is utilized in the study of cancer, inflammation, or autoimmune diseases that are</p>

<p>HIF-2α-IN-7 is a hypoxia inducible factor 2α (HIF-2α) inhibitor.</p>

<p>GJG057 is a highly efficient and selective Leukotriene C4 synthase (LTC4S) inhibitor with an IC50 of 44 nM in human whole blood LTC4 release assays and oral activity. It demonstrates anti-inflammatory efficacy in a mouse asthma exacerbation model and can be used for the treatment of allergic inflammation.</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>CAII-IN-1 (3n) is a selective bovine CA-II inhibitor with 10.3 μM IC50, used in carbonic anhydrase disorder studies.</p>

<p>2R,4R-Sacubitril is the impurity of Sacubitril. Sacubitril is used in combination with valsartan for the treatment of patients with heart failure.</p>

<p>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.</p>

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

<p>FAAH/MAGL-IN-1 (SIH 3) inhibits FAAH &amp; MAGL with IC50 of 31 &amp; 29 nM, useful in neuropathic pain research.</p>

<p>PLAP-IN-1: Potent, selective inhibitor of PLAP, IC50 of 32 nM; doesn't notably inhibit TNAP.</p>

<p>Squalestatin 3 is an inhibitor of squalene synthase.</p>

<p>Lp-PLA2-IN-5 inhibits Lp-PLA2 and PAF-AH, potentially useful in Alzheimer's and atherosclerosis studies.</p>

<p>Hcyb1 specifically inhibits PDE2A with 0.57 μM IC50, over 250x selective, and has neuroprotective and antidepressant effects.</p>

<p>hDHODH-IN-10: selective oral inhibitor of hDHODH (IC50: 10.9 nM); blocks cancer cell growth, aids cancer research.</p>

<p>Dual hMAO-B/MB-COMT inhibitor, IC50: 2.5 μΜ (hMAO-B), 3.84 μΜ (MB-COMT); potential in Parkinson's research.</p>

<p>4-(4-Bromophenyl)-4-hydroxypiperidine (BPHP) is a metabolite of Bromperidol (BRO), produced through the N-dealkylation of BRO.</p>

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

<p>CK2 inhibitor 3: potent CK2 blocker, IC50 of 280 nM, suppresses tumor cell growth, highly selective among 320 kinases.</p>

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

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

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

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

<p>β-Glucuronidase/hCAII-IN-2 (Compound 12e) is a compound that effectively inhibits both β-glucuronidase and human Carbonic Anhydrase II (hCA II), exhibiting IC50</p>

<p>Lunacalcipol is used for the treatment of Secondary Hyperparathyroidism.</p>

<p>RXR antagonist 1 is a Retinoid X Receptor (RXR) modulator that exhibits high RXR antagonism (pA2: 8.06). RXR antagonist 1 can be used to study type 2 diabetes.</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>PTP1B-IN-16: selective benzimidazole inhibitor of PTP1B, Ki: 12.6 μM, potential for type 2 diabetes research.</p>

<p>PAT-347 is a potent inhibitor of Autotaxin, an enzyme linked to cell survival and diseases like cancer and fibrosis.</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>Rivaroxabandiol is a metabolite of Rivaroxaban, which is a potent and selective direct inhibitor of coagulation factor Xa (FXa) with an IC50 of 0.7 nM and a Ki of 0.4 nM.</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>RORγ-IN-2 (Compound 22) is an inhibitor of RORγ, with a Ki value of 16.6 nM for hRORγ. It is useful for research in IL-17-dependent autoimmune diseases.</p>

<p>EB-0150 inhibits ER α-Glu I/II (IC50: 0.73/0.0337 μM), is an N-substituted valerian with antiviral effects, and has drug discovery potential.</p>

<p>GSK 366 is a potent kynurenine-3-monooxygenase (KMO) inhibitor (IC50s: 0.7 nM and 2.3 nM for P. fluorescens-KMO and human KMO).</p>

<p>CAII-IN-3, a thiosemicarbazone, potently inhibits CA-II with an IC50 of 13.4 μM.</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>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>PDE4B-IN-3 is a potent inhibitor of PDE4B (IC50: 0.94 μM) and exhibits anti-inflammatory effects.</p>

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

<p>Oxythiamin diphosphate ammonium is a potent inhibitor of transketolase (TK).</p>

<p>'3'-Hydroxy Repaglinide, a CYP2C8 metabolite of Repaglinide, treats type II diabetes.</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>Ro 23-9358 is a potent inhibitor of secretory phospholipase A2, exhibiting anti-inflammatory properties.</p>

<p>PTP1B-IN-3 diammonium, an oral enzyme inhibitor, has potent antidiabetic and anticancer effects, with a 120 nM IC50.</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>NTPDase-IN-2 inhibits h-NTPDase-2/-8 (IC50: 0.04, 2.27 µM), non-competitive for h-NTPDase-1/-2 (Km: 74 µM); useful in cancer, immune, bacterial research.</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>Dual inhibitor hMAO-B/MB-COMT-IN-2 targets hMAO-B (IC50: 4.27μM) &amp; MB-COMT (IC50: 2.69μM), aids in neurodegenerative 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>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>CYP1B1-IN-2 (compound 9j) is a highly potent and selective inhibitor of CYP1B1, a cytochrome P450 enzyme. It exhibits an IC50 value of 0.52 nM [1].</p>

<p>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.</p>

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

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

<p>(2S,4S)-Sacubitril (Sacubitril Impurity C) is a stereoisomer derived from Sacubitril which is a potent NEP inhibitor.</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>ATX inhibitor 22 is a novel inhibitor of ATX (autotaxin) (IC50: 218.9 μM) that lacks inhibitory activity against LPAR1.</p>

<p>hCAII-IN-3 inhibits key hCA isoforms with Ki: hCA I (403.8 nM), hCA II (5.1 nM), hCA IX (10.2 nM), hCA XII (5.2 nM); shows anticancer potential.</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>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>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>(Rac)-8-Hydroxy-efavirenz is a metabolite of Efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of HIV-1.</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>