competitively

FIDAS-5, a potent and orally active methionine S-adenosyltransferase 2A (MAT2A) inhibitor with an IC50 of 2.1 μM, competitively inhibits S-adenosylmethionine (SAM) binding to MAT2A. It exhibits anticancer activities.

Hydroxycitric acid tripotassium hydrate (Potassium citrate monohydrate) effectively inhibits stones formation and also inhibits HIF, and has antioxidation, anti-inflammation, and anti-tumor effects. Hydroxycitric acid tripotassium hydrate(Potassium citrate monohydrate) (Potassium citrate monohydrate) is the major active ingredient of Garcinia cambogia and a derivative of citric acid. Hydroxycitric acid tripotassium hydrate(Potassium citrate monohydrate) competitively inhibits ATP citrate lyase with weight loss benefits.

Sitagliptin (MK0431), a new oral hypoglycemic (anti-diabetic drug), is a new dipeptidyl peptidase-4 (DPP-4) inhibitor. This enzyme-inhibiting drug is used either alone or in combination with metformin or thiazolidinedione for treatment of type 2 diabetes mellitus. The drug can competitively inhibit a protein/enzyme and DPP-4, that leads to an incremental amount of active incretins (GLP-1 and GIP), the diminished amount of release of glucagon and increased release of insulin.

Roflumilast (APTA 2217) is an orally available, long-acting inhibitor of phosphodiesterase (PDE) type 4 (PDE4), with anti-inflammatory and potential antineoplastic activities. Upon administration, roflumilast and its active metabolite roflumilast N-oxide selectively and competitively bind to and inhibit PDE4, which leads to an increase of both intracellular levels of cyclic-3', 5'-adenosine monophosphate (cAMP) and cAMP-mediated signaling.

Adenosine 5'-diphosphate (ADP) induces human platelet aggregation and non-competitively blocks the stimulated human platelet adenylate cyclase.

N-Desethyl Chloroquine Hydrochloride ((±)-Desethylchloroquine 2HCl) is a desethylchloroquine derivative. desethylchloroquine competitively inhibits cyp2d1 /6-mediated reactions in vitro and in vivo.

Dalvastatin (RG-12561) is an orally available inhibitor of HMG-CoA reductase and cholesterol-lowering synthesis.Dalvastatin competitively inhibits rat hepatic HMG-CoA reductase with an IC50 value of 3.4 nmol / l. Dalvastatin inhibits cholesterol biosynthesis in liver sections in rat experiments with an ED50 value of 0.9.

MK-2461 is a novel inhibitor that targets multiple proteins and competitively binds to ATP sites, specifically inhibiting the activated c-Met protein with an average inhibitory concentration (IC50) of 2.5 nM.

Allopurinol riboside is a metabolite of allopurinol with potency against parasites. Allopurinol riboside competitively inhibits the action of purine nucleoside phosphorylase on inosine with a Ki of 277 μM.

Vanillin (Zimco) is a single molecule extracted from vanilla beans and also a popular odor used widely in perfume, food and medicine.Vanillin can reversibly and non-competitively inhibit the cellulase activity at appropriate concentrations and the value of IC50 was estimated to be 30 g/L.Vanillin protects KSC from UVB irradiation and its effects may occur through the suppression of downstream step of MDM2 in UVB irradiation-induced p53 activation. Vanillin also inhibits yeast growth and fermentation.

Emedastine (LY188695) is a second generation, selective histamine H1 receptor antagonist with anti-allergic activity. Emedastine reversibly and competitively blocks histamine by binding to H1 receptors, thus blocking its downstream activity. As a result this agent interferes with mediator release from mast cells either by inhibiting calcium ion influx across mast cell/basophil plasma membrane or by inhibiting intracellular calcium ion release within the cells. In addition, emedastine may also inhibit the late-phase allergic reaction mediated through leukotrienes or prostaglandins, or by producing an anti-platelet activating factor effect. Upon ocular administration, emedastine causes a dose-dependent inhibition of histamine-stimulated vascular permeability in the conjunctiva. Emedastine does not affect adrenergic, dopamine, or serotonin receptors.

Stiripentol (BCX2600) (STP) is an anticonvulsant agent, which can inhibit N-demethylation of CLB to NCLB mediated by CYP3A4 (noncompetitively) and CYP2C19 (competitively) with Ki of 1.59/0.516 μM and IC50 of 1.58/3.29 μM, respectively.

Dapagliflozin (BMS-512148) is a selective sodium-glucose co-transporter subtype 2 (SGLT2) inhibitor with antihyperglycemic activity.

Kobe0065 is a novel and effective small-molecule compound inhibiting Ras–Raf interaction by SBDD; shows potent activity to competitively inhibit the binding of H-Ras·GTP to c-Raf-1 RBD with a Ki value of 46 ± 13 μM.

Penciclovir (BRL 39123) is a Herpesvirus Nucleoside Analog DNA Polymerase Inhibitor. In HSV infected cells, penciclovir is phosphorylated by viral thymidine kinase and subsequently converted by cellular kinases into the active metabolite, penciclovir triphosphate, which competitively inhibits viral HSV polymerase by blocking deoxyguanosine triphosphate substrate binding. As a result, herpes viral DNA synthesis and replication are selectively inhibited.

Gambogic Acid (Guttic Acid) ( EC50=0.78-1.64 uM) activates caspases. Gambogic Acid competitively suppresses Bcl-XL, Bcl-2, Bcl-W, Bcl-B, Bfl-1 and Mcl-1. The IC50s of Gambogic Acid for Bcl-XL, Bcl-2, Bcl-W, Bcl-B, Bfl-1 and Mcl-1 are 1.47, 1.21, 2.02, 0.66, 1.06 and 0.79 uM, respectively.

MK-571 sodium (L-660711 sodium salt) is a selective, orally active antagonist of the CysLT1 receptor. MK-571 sodium is a multidrug resistance protein-2 (ABCC2, Mrp2) inhibitor used to demonstrate the role of Mrp2 in the cellular efflux of drugs, xenobiotics, and their conjugates. MK-571 sodium can inhibit the synthesis of K-4′-O-GlcA (19.7 μM). MK571 dose-dependently inhibits the intracellular biosynthesis of all flavonol sulphates and glucuronides by Caco-2 cells. MK-571 sodium significantly inhibits phase-2 conjugation of kaempferol by cell-free extracts of Caco-2, and production of kaempferol-4′-O-glucuronide was competitively inhibited. In addition to inhibiting MRP2, MK571 is a potent inhibitor of enterocyte phase-2 conjugation.

Doxylamine Succinate is a pyridine derivate histamine H1 antagonist with pronounced sedative properties. Doxylamine succinate (Decapryn) competitively blocks the histamine H1 receptor and limits the typical allergic and anaphylactic responses, including bronchoconstriction, vasodilation, increased capillary permeability, and spasmodic contraction of the gastrointestinal smooth muscle, caused by actions of histamine on bronchial and gastrointestinal smooth muscles, and on capillaries. This drug also prevents histamine-induced pain and itching of the skin and mucous membranes.

Torin 1 is an effective inhibitor of mTORC1/2 with (IC50: 2 nM/10 nM); has 1000-fold selectivity for mTOR than PI3K.

Jasplakinolide(Jaspamide), a naturally occurring cyclic peptide from marine sponges, is a potent inducer of actin polymerization.Jasplakinolide exhibits antifungal and antitumor activity and stabilizes pre-existing actin filaments. Jasplakinolide competitively binds to F-actin with the ghost pen cyclic peptide and has a Kd value of 15 nM for F-actin.

RO-3306 is a selectivity ATP-competitive CDK1 inhibitor (Ki: 20 nM). The selectivity of RO-3306 for CDK1 is >15-fold higher than a diverse panel of human kinases.

Col003 is a selective and potent inhibitor of Hsp47 and competitively binds to the collagen-binding site on Hsp47 (IC50: 1.8 μM). It can be used for the investigation of fibrosis.

Rosuvastatin (ZD 4522) is an antilipemic agent that competitively inhibits hydroxymethyl-glutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonic acid, the rate-limiting step in cholesterol biosynthesis. Rosuvastatin belongs to a class of medications called statins and is used to reduce plasma cholesterol levels and prevent cardiovascular disease.

Bestatin (Ubenimex) competitively inhibits many aminopeptidases, including B, N and leucine aminopeptidases. Ubenimex is a microbial metabolite and dipeptide with potential immunomodulatory and antitumor activities. Aminopeptidases has been implicated in the process of cell adhesion and invasion of tumor cells. Therefore, inhibiting aminopeptidases may partially attribute to the antitumor effect of ubenimex. This agent also activates T lymphocyte, macrophage, and bone marrow stem cell as well as stimulates the release of interleukin-1 and -2, thus further enhances its antitumor activity.

KN-93 is a selective inhibitor of Ca2+/calmodulin-dependent kinase II (CaMKII), competitively blocking CaM binding to the kinase.

Talabostat (PT100, Val-boroPro) is a potent, nonselective and orally available dipeptidyl peptidase IV (DPP-IV) inhibitor with a Ki of 0.18 nM. Talabostat is a nonselective DPP-IV inhibitor, inhibiting DPP8/9, FAP, DPP2 and some other DASH family enzymes essentially as potently as it inhibits DPP-IV[1]. Talabostat stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. The inhibition of two serine proteases, DPP8 and DPP9, activates the proprotein form of caspase-1 independent of the inflammasome adaptor ASC[2]. Talabostat competitively inhibits the dipeptidyl peptidase (DPP) activity of FAP and CD26/DPP-IV, and there is a high-affinity interaction with the catalytic site due to the formation of a complex between Ser630/624 and the boron of talabostat[3]. Talabostat can stimulate immune responses against tumors involving both the innate and adaptive branches of the immune system. In WEHI 164 fibrosarcoma and EL4 and A20/2J lymphoma models, PT-100 causes regression and rejection of tumors. The antitumor effect appears to involve tumor-specific CTL and protective immunological memory. Talabostat treatment of WEHI 164-inoculated mice increases mRNA expression of cytokines and chemokines known to promote T-cell priming and chemoattraction of T cells and innate effector cells[3]. Talabostat treated mice show significant less fibrosis and FAP expression is reduced. Upon PT100 treatment, significant differences in the MMP-12, MIP-1α, and MCP-3 mRNA expression levels in the lungs are also observed. Treatment with PT100 in this murine model of pulmonary fibrosis has an anti-fibro-proliferative effect and increases macrophage activation[4]. [1]. Connolly BA, et al. Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potencyand in vivo efficacy and safety. J Med Chem. 2008 Oct 9;51(19):6005-13. [2]. Okondo MC, et al. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 2017 Jan;13(1):46-53. [3]. Adams S, et al. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80. [4]. Egger C, et al. Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis. Eur J Pharmacol. 2017 Aug 15;809:64-72.

MEY-003, an Autotaxin (ATX) inhibitor, exhibits EC50 values of 460 nM for hATX-β and 1.09 μM for hATX-ɣ (analysis with LPC18:1), demonstrating its potency against these isoforms. It acts non-competitively with a K i of 432 nM, making it suitable for research into diseases where ATX is implicated [1].

Ordesekimab (AMG 714) is a human IgG1 κ-anti-IL-15 (Interleukin Related) monoclonal antibody. Ordesekimab binds competitively to IL-15, inhibiting the interaction of IL-15 with the common gamma chain of the IL-2Rβ and IL-15 receptor complex, but not with the IL-15Rα chain. Ordesekimab can be used to study non-reactive celiac disease (NRCD).

J5 peptide, an MBP inhibitor, competitively inhibits the binding of MBP 85-99 to HLA-DR2, and mitigates PLP 139-151/MBP 85-99-induced experimental autoimmune encephalomyelitis (EAE) in mice. It is utilized in research pertaining to inflammatory and immune diseases [1].

Suberoylanilide hydroxamic acid (SAHA) is a class I and class II histone deacetylase (HDAC) inhibitor that binds directly to the catalytic site of the enzyme thereby blocking substrate access. [1] coumarin-Suberoylanilide hydroxamic acid (c-SAHA) is a SAHA derivative where the anilino cap group is replaced by 7-amino-4-methylcoumarin to produce a fluorescent probe that competitively binds HDAC. [2] The fluorescence excitation and emission maxima of free c-SAHA is 325 and 400 nm

3'-Deoxyuridine-5'-triphosphate trisodium (3'-dUTP trisodium) is a nucleotide analogue that suppresses DNA-dependent RNA polymerases I and II activity. It competitively obstructs the inclusion of UTP into RNA, demonstrating strong inhibition with a dissociation constant (Ki) of 2.0 μM[1].

KN-92 hydrochloride is an inactive derivative of KN-93. KN-93 is a selective Ca2+/calmodulin-dependent kinase II (CaMKII) inhibitor, competitively blocking CaM binding to the kinase with Ki of 370 nM.

Antagonist of 14.3.3 proteins (KD ≈80 nM). Competitively inhibits 14.3.3-ligand interactions without requiring phosphorylation. Blocks the ability of 14.3.3 to bind to target proteins such as Raf-1, Bad, ASK1 and exoenzyme S.

ERAP1-IN-1 is an endoplasmic reticulum aminopeptidase 1 (ERAP1) inhibitor. ERAP1-IN-1 allosterically activates ERAP1’s hydrolysis of fluorogenic and chromogenic amino acid substrates but competitively inhibits its activity toward a nonamer peptide representative of physiological substrates.

Dostarlimab (TSR-042) is a humanized monoclonal antibody targeting PD-1 with high affinity, designed to block its interaction with ligands PD-L1 and PD-L2. By competitively inhibiting these interactions, it achieves IC50 values of 1.8 nM for PD-L1 and 1.5 nM for PD-L2, demonstrating its effective inhibition capabilities [1].

EAC3I, an autocamtide-3 derived inhibitory peptide with the sequence KKALHRQEAVDAL, is a bioactive peptide that mimics the autoinhibitory region of the CaMKII regulatory domain (residues 278–290). It functions by competitively binding to the enzyme's catalytic site.

Isotanshinone IIA, could non-competitively inhibit Protein Tyrosine Phosphatase 1B (PTP1B) activity with an IC50 0f 11.4 μM. is an abietane-type diterpene metabolite.

Aplithianines A effectively inhibits J-PKAcα with an IC50 value of 1 μM and displays higher potency against wild-type PKA, achieving an IC50 of 84 nM by competitively interacting with the ATP pocket [1].

Thrombospondin-1 (TSP-1)-derived CD36 binding motif is a bioactive peptide cyclized by a disulfide bond, critical for TSP-1-CD36 interaction. Involved in cancer metastasis, tumor adhesion, and angiogenesis, this matrix-bound glycoprotein-origin peptide competitively inhibits platelet aggregation and tumor metastasis.

Cell-permeable version of dynamin inhibitory peptide, an inhibitor of the GTPase dynamin that competitively blocks binding of dynamin to amphiphysin, preventing endocytosis. Reduces NMDA receptor internalization.

SB 203580 sulfone, an analog of the p38 MAP kinase inhibitor SB 203580, inhibits IL-1 production in monocytes and binds competitively with CSAID binding proteins (CSBP), inhibiting stress response signaling. It exhibits an IC50 of 0.2 μM for IL-1 inhibition and 0.03 μM for CSBP-mediated signaling inhibition [1].

Rp-cAMPS competitively inhibits the cAMP-induced activation of cAMP-dependent protein kinase (PKA).

Selective and competitive nociceptin receptor antagonist, devoid of any agonist activity. Binds selectively to recombinant nociceptin receptors (pKi = 8.4), and competitively antagonizes the actions of nociceptin in vitro and in vivo.

KN-92 phosphate (KN92-H3PO4) is an inactive derivative of KN-93. KN-93 is a selective inhibitor of Ca2+/calmodulin-dependent kinase II (CaMKII), competitively blocking CaM binding to the kinase (Ki = 370 nM).

N-Nitrosodicyclohexylamine (NDCHA), an N-nitrosocompound, exhibits anti-androgenic activity by competitively binding to the androgen receptor (AR) in opposition to 5α-dihydrotestosterone and reducing AR protein levels [1].

Akuammigine has in vitro antimalarial activity. Akuammigine competitively antagonizes the effect of noradrenaline on postsynaptic alpha-adrenoceptors, yielding pA2 values of 4.68. Akuammidine also shows a preference for mu-opioid binding sites with Ki val

L-Allooctopine competitively inhibits D-octopine [1].

Cardol triene is a phenol found in cashew nut shell liquid that competitively and irreversibly inhibits mushroom tyrosinase (IC50 = 22.5 μM). It is schistosomicidal, killing 25, 75, and 100% of S. mansoni worms after 24 hours when used at concentrations of 50, 100, or 200 μM, respectively. It has been used as a starting material for the synthesis of bis-benzoxazines.

Fenclofenac is a non-steroidal anti-inflammatory agent that competitively supresses the binding of thyroxine(T4) and triiodothyronine (T3) by thyroxine-binding globulin(TBG).

Labetalone hydrochloride is an orally effective adrenergic receptor blocking drug that competitively antagonizes both α and β receptor sites.