Evogliptin is a DPP4 inhibitor for type 2 diabetes and inflammatory research
**Background**
Type 2 diabetes mellitus is a chronic metabolic disorder characterized by insulin resistance and progressive pancreatic beta-cell failure, leading to persistent hyperglycemia. Dipeptidyl peptidase-4 (DPP4) is a key enzyme that degrades incretin hormones, such as glucagon-like peptide-1 (GLP-1), which are essential for stimulating insulin secretion and suppressing glucagon release. Consequently, the inhibition of DPP4 has become a primary therapeutic strategy to maintain glycemic control and prevent diabetic complications. Beyond metabolic regulation, DPP4 is also involved in immune modulation and inflammatory responses in various organs, including the liver and kidneys. In this context, we will introduce a potent DPP4 inhibitor – Evogliptin.
**Definition**
Evogliptin (DA-1229) tartrate is an orally active DPP4 inhibitor designed to provide significant and sustained hypoglycemic effects. According to the Evogliptin description, it targets the DPP-4 enzyme to regulate glucose homeostasis and modulate inflammatory signals.
**In Vitro and In Vivo Studies**
The Evogliptin biological activity has been demonstrated across multiple experimental models. In vitro studies showed that Evogliptin tartrate (2.49 mM; 12 h) efficiently inhibited mDPP4 (membrane DPP4) enzymatic activity in PWM-induced H9 Th1 cells in a dose-dependent manner, without affecting cell viability or the cytokine profile. Furthermore, research into Evogliptin Autophagy revealed that the compound prevents inflammatory and fibrotic signaling in primary hepatocytes of ATG7 f/f-Cre+ mice by inducing autophagy.
Evogliptin in vivo efficacy was evaluated using male ICR mice in a high-fat diet/streptozotocin (HFD/STZ) model of type 2 diabetes. Administration of Evogliptin tartrate (100, 300 mg/kg; single daily via animal feedings for 10 weeks) resulted in a decrease in blood glucose levels starting from the second week of treatment. At a dosage of 300 mg/kg, the compound significantly reduced HbA1c levels and decreased 6 h-fasted blood glucose levels in a dose-dependent manner, thereby improving glucose intolerance and insulin resistance. In conclusion, Evogliptin is a potent DPP4 inhibitor that holds promise for the treatment of type 2 diabetes, chronic liver inflammation, renal impairment, and osteoporosis.
Keywords
Evogliptin, 1222102-51-3, DA-1229, DA1229, DA 1229, Dipeptidyl Peptidase, Autophagy, DPP, type 2 diabetes, osteoporosis, renal impairment, chronic liver inflammation, H9 Th1, hepatocytes, Inhibitor
References
[1] Yoon H, et al. Effects of the Antidiabetic Drugs Evogliptin and Sitagliptin on the Immune Function of CD26/DPP4 in Th1 Cells. Biomol Ther (Seoul). 2021 Mar 1;29(2):154-165.
[2] Seo H Y, et al. Evogliptin Directly Inhibits Inflammatory and Fibrotic Signaling in Isolated Liver Cells. International Journal of Molecular Sciences, 2022, 23(19): 11636.
[3] Kim TH, et al. Hepatic role in an early glucose-lowering effect by a novel dipeptidyl peptidase 4 inhibitor, evogliptin, in a rodent model of type 2 diabetes. Eur J Pharmacol. 2016 Jan 15;771:65-76.
[4] Tan X, et al. Evogliptin: a new dipeptidyl peptidase inhibitor for the treatment of type 2 diabetes. Expert Opin Pharmacother. 2016 Jun;17(9):1285-93.
**Background**
Ebola virus disease (EVD) is a severe, often fatal illness in humans, characterized by systemic inflammation and hemorrhagic fever. The pathogenesis of the virus is heavily dependent on the Ebola virus glycoprotein (EBOV-GP), which mediates viral attachment, fusion, and entry into host cells. Because EBOV-GP is essential for the viral life cycle, it serves as a primary target for the development of neutralizing antibodies and vaccines. Effective therapeutic interventions aim to block the interaction between the glycoprotein and host cell receptors to prevent infection and reduce viral load. In this context, we will introduce a mouse/human chimeric monoclonal antibody against EBOV-GP – Cosfroviximab.
**Definition**
Cosfroviximab (c13C6-FR1) is a mouse/human chimeric monoclonal antibody of the Human IgG1 kappa isotype that specifically targets the Ebola virus glycoprotein (EBOV-GP). According to the Cosfroviximab description, this antibody has a molecular weight of 145.34 kDa and is designed for high specificity against the EBOV target.
**Applications and Studies**
Cosfroviximab is utilized in various research applications, including ELISA, FACS, and functional assays to evaluate its neutralizing capabilities. Regarding Cosfroviximab biological activity, the antibody is engineered to bind to the viral glycoprotein, thereby inhibiting the entry of the virus into target cells. Research into thermostable vaccine formulations has highlighted the importance of maintaining antibody stability when lyophilized with adjuvants such as aluminum hydroxide to ensure efficacy in diverse environmental conditions. For researchers requiring precise experimental parameters, the Cosfroviximab protocol suggests reconstitution or dilution using sterile PBS or saline. In conclusion, Cosfroviximab is a potent chimeric monoclonal antibody that serves as a critical tool for studying Ebola virus neutralization and developing therapeutic strategies against EVD.
Keywords
Cosfroviximab, 1792982-57-0, c13C6-FR1, Filovirus, Inhibitor, inhibitor, inhibit
References
**Background**
Glutamate receptors are a group of ionotropic receptors that play a fundamental role in synaptic transmission and plasticity within the central nervous system. Among these, the GluR5 subunit of the AMPA/kainate receptor family is of particular interest due to its distinct pharmacological properties and its role in modulating excitatory neurotransmission. Understanding the specific activation mechanisms of GluR5 is crucial for researching neurological disorders and the molecular basis of synaptic signaling. In this context, we will introduce a selective glutamate receptor GluR5 activator – ATPA.
**Definition**
ATPA is a selective GluR5 activator with a high potency for the wild-type receptor, exhibiting an EC50 value of 0.66 μM for GluR5wt.
**In Vitro Studies**
The ATPA biological activity is characterized by its ability to activate various GluR5 variants with differing efficiencies. According to the ATPA description, the compound shows EC50 values of 9.5 μM for GluR5(S741M), 1.4 μM for GluR5(S721T), 23 μM for GluR5(S721T, S741M), 32 μM for GluR5(S741A), 18 μM for GluR5(S741L), and 14 μM for GluR5(S741V). These results indicate that the activation of the receptor is significantly controlled by the serine 741 residue. Furthermore, ATPA in vitro data demonstrates that the compound also activates GluR1 variants, although generally with lower potency. Specifically, it activates GluR1wt, GluR1(M722S), GluR1(T700S), GluR1(T700S, M722S), and GluR1(M722A) with EC50 values of 62, 4.6, 97, 14, and 97 μM, respectively. In conclusion, ATPA is a selective activator of the glutamate receptor GluR5 whose efficacy is modulated by specific amino acid residues.
Keywords
ATPA, 140158-50-5, iGluR, Ionotropic glutamate receptors, Inhibitor, inhibitor, inhibit
References
**Background**
Cytochrome P450 1A2 (CYP1A2) is a critical member of the cytochrome P450 superfamily of enzymes, primarily expressed in the liver. It plays a pivotal role in the phase I metabolism of various endogenous compounds and a wide array of exogenous substances, including pharmaceuticals and environmental pollutants. Due to its involvement in the bioactivation of pro-carcinogens and the metabolism of clinically significant drugs, CYP1A2 is a key target in pharmacological and toxicological research. Understanding the inhibition of this enzyme is essential for predicting drug-drug interactions and assessing the metabolic clearance of therapeutic agents. In this context, we will introduce a γ-lactone compound used for the study of this enzyme – γ-Dodecanolactone.
**Definition**
γ-Dodecanolactone is a γ-lactone compound that acts as an inhibitor of CYP1A2, exhibiting an IC50 value of 58 μM and a pIC50 value of 4.24.
**In Vitro Studies**
Regarding the γ-Dodecanolactone description, this compound is characterized by a molecular weight of 198.30 and the γ-Dodecanolactone formula C12H22O2. In terms of γ-Dodecanolactone biological activity, research has focused on its capacity to modulate the activity of the cytochrome P450 system. Specifically, in vitro evaluations have demonstrated that γ-Dodecanolactone effectively inhibits CYP1A2 with an IC50 of 58 μM. These findings were part of a broader study utilizing predictive three-dimensional quantitative structure-activity relationship (3D-QSAR) models to identify and characterize potent inhibitors of the CYP1A2 enzyme. Such data are invaluable for researchers investigating the structural requirements for enzyme binding and the development of selective inhibitors. In conclusion, γ-Dodecanolactone is a γ-lactone compound that serves as a useful tool for the research of diseases and metabolic processes related to the CYP1A2 enzyme.
Keywords
γ-Dodecanolactone, 2305-05-7, Cytochrome P450, CYPs, γ-lactone compound, CYP1A2, Inhibitor, inhibitor, inhibit
References
**Background**
Cryopreservation is a critical technique in biomedical research and reproductive medicine, allowing for the long-term storage of cells, tissues, and gametes. However, the process of freezing and thawing can lead to severe cellular damage caused by the formation of intracellular ice crystals and osmotic stress. To mitigate these effects, cryoprotective agents (CPAs) are employed to stabilize cell membranes and prevent lethal ice formation. In the context of reproductive biology, maintaining the viability and motility of sperm cells during freezing is essential for successful fertilization and genetic research. Therefore, we will introduce a versatile amide compound used as a cryoprotectant – Lactamide.
**Definition**
Lactamide (2-Hydroxypropanamide) is an amide compound with the Lactamide formula C3H7NO2 and a molecular weight of 89.09.
**Experimental Applications**
According to the Lactamide description, this compound serves as an effective cryoprotectant in specialized biological applications. Specifically, it is employed in experiments focused on the cryopreservation of white rabbit sperm to preserve cellular integrity and functional motility. Researchers seeking detailed Lactamide technical information can utilize this compound to optimize freezing protocols and improve post-thaw recovery rates in animal models. Furthermore, the chemical properties of Lactamide make it a valuable building block in synthetic chemistry; for instance, it has been involved in the synthesis of trifluoroatrolactamide libraries via one-pot Passerini/hydrolysis reaction sequences to evaluate fungicidal activities. In conclusion, Lactamide is a cryoprotectant and synthetic intermediate used in reproductive biology and chemical synthesis research.
Keywords
Lactamide, 2043-43-8, 2-Hydroxypropanamide, Biochemical Assay Reagents, Acetamide, Cryopreservation, Rabbit spermatozoa, Glycerol, Dimethylsulfoxide (DMSO), Forward progressive motility, Plasma membrane integrity, Inhibitor, inhibitor, inhibit
References
**Background**
N-glycosylation is a critical post-translational modification process where carbohydrate chains are attached to proteins, playing a vital role in protein folding, stability, and cell signaling. The STT3A and STT3B subunits are the catalytic cores of the oligosaccharyltransferase (OST) complex, which is responsible for the transfer of the glycan precursor to nascent polypeptide chains. Dysregulation of N-glycosylation is frequently associated with various pathologies, including viral infections, where viruses hijack the host’s glycosylation machinery to facilitate entry and evade the immune system. Furthermore, aberrant glycosylation is a hallmark of many malignancies and neurodegenerative disorders. Consequently, targeting STT3A/B has emerged as a promising strategy for therapeutic intervention. In this context, we will introduce a STT3A/B inhibitor – (R,S)-STT3A/B-IN-1.
**Definition**
(R,S)-STT3A/B-IN-1 is a STT3A/B inhibitor that serves as the racemate of STT3A/B-IN-1. According to the (R,S)-STT3A/B-IN-1 description, this compound is designed to inhibit N-glycosylation to modulate disease progression.
**Mechanism of Action**
The (R,S)-STT3A/B-IN-1 formula is $\text{C}_{19}\text{H}_{21}\text{N}_3\text{O}_2\text{S}$, with a molecular weight of 355.45. This compound acts by inhibiting the activity of STT3A and STT3B, thereby blocking the N-glycosylation pathway. By disrupting this essential modification, (R,S)-STT3A/B-IN-1 can interfere with the production of functional glycoproteins necessary for viral replication and tumor cell survival.
**Experimental Studies**
Based on the (R,S)-STT3A/B-IN-1 biological activity, this sulfoximine-based modulator demonstrates significant potential in the research of viral diseases, (R,S)-STT3A/B-IN-1 Cancer, and neurodegenerative disorders. By inhibiting the OST complex, the compound effectively reduces the N-glycosylation of target proteins, which is a critical step in the pathogenesis of these conditions. In conclusion, (R,S)-STT3A/B-IN-1 is a promising STT3A/B inhibitor for the study and treatment of various glycosylation-dependent diseases.
Keywords
(R,S)-STT3A/B-IN-1, 3067185-00-3, Drug Isomer, Virus Protease, N-Glycosylation, Inhibitor, inhibitor, inhibit
References
**Background**
Spasticity is a condition characterized by increased muscle tone and stiffness, often resulting from upper motor neuron lesions. It is a common complication in patients suffering from multiple sclerosis (MS), stroke, and spinal cord injury (SCI), significantly impairing mobility and quality of life. Beyond its application in neurology, recent research has explored the potential of certain muscle relaxants in oncology. Specifically, the inhibition of signaling pathways such as AKT and Wnt3a/$\beta$-catenin has emerged as a strategy to suppress the proliferation and metastasis of lung cancer cells. In this context, we will introduce a centrally acting $\alpha_2$-adrenoceptor agonist – Tizanidine.
**Definition**
Tizanidine hydrochloride is an orally effective skeletal muscle relaxant and $\alpha_2$-adrenoceptor agonist with an $\text{IC}_{50}$ value of 6.9 nmol.
**In Vitro and In Vivo Studies**
The Tizanidine description highlights its primary mechanism as the inhibition of excitatory amino acid release (glutamate and aspartate) from presynaptic terminals of spinal cord interneurons. Regarding Tizanidine in vitro activity, the compound is mainly metabolized by cytochrome CYP1A2, exhibiting a half-life of 50 min in human liver microsomes. In lung cancer research, Tizanidine (20 $\mu$M; 0-72 h) inhibits the proliferation, migration, and invasion of A549 cells. This effect is mediated by the upregulation of Nischarin, which leads to the inactivation of the Wnt3a/$\beta$-catenin pathway and the inhibition of AKT and mTOR phosphorylation. Furthermore, treatment of A549 cells with 20 $\mu$M Tizanidine for 48 h significantly increases the apoptosis rate, characterized by decreased Bcl-2 expression and increased Bax and Caspase-3 expression.
Tizanidine in vivo studies have demonstrated its efficacy in managing neuropathic pain. In a spinal nerve ligation (SNL) model using Wistar rats, oral administration of Tizanidine (0.02, 0.2, 2, and 20 mg/kg) for 14 days produced a dose-dependent analgesic effect. Notably, this effect was significantly stronger in female rats than in males, with estrogen identified as a key contributing factor. In ovarian removal (OVX) female rats, the TZN AUC decreased to 90 g·h (a 50% reduction compared to intact females), a result that was reversed following E2 replacement therapy. In conclusion, Tizanidine is a versatile $\alpha_2$-adrenoceptor agonist with potent muscle relaxant, analgesic, and antitumor properties.
Keywords
Tizanidine, 64461-82-1, Adrenergic Receptor, Apoptosis, Akt, Wnt, β-catenin, Beta Receptor, PKB, Protein kinase B, Beta catenin, Adrenergic receptors, Allodynia, Neuropathic pain, Sex-dependent
References
[1] Kamen L, et al. A practical overview of tizanidine use for spasticity secondary to multiple sclerosis, stroke, and spinal cord injury. Curr Med Res Opin. 2008 Feb;24(2):425-39.
[2] Granfors MT, Backman JT, Laitila J, Neuvonen PJ. Tizanidine is mainly metabolized by cytochrome p450 1A2 in vitro. Br J Clin Pharmacol. 2004 Mar;57(3):349-53. doi: 10.1046/j.1365-2125.2003.02028.x. PMID: 14998432; PMCID: PMC1884447.
[3] Zhao L, Zhao G, Xue Q. Tizanidine (Hydrochloride) Inhibits A549 Lung Cancer Cell Proliferation and Motility Through Regulating Nischarin. Onco Targets Ther. 2020 Jan 10;13:291-298.
[4] Rodríguez-Palma EJ, et al. Sex-dependent antiallodynic effect of α2 adrenergic receptor agonist tizanidine in rats with experimental neuropathic pain. Eur J Pharmacol. 2022 Apr 5;920:174855.
**Background**
Vitamin B6 is an essential nutrient that serves as a cofactor for numerous enzymatic reactions in the human body, particularly those involving amino acid metabolism. Among its various forms, pyridoxal plays a critical role as a neuroprotectant. Research has indicated that deficiencies or imbalances in vitamin B6 metabolism can contribute to neurological dysfunction. Specifically, carpal tunnel syndrome (CTS), a condition characterized by compression of the median nerve at the wrist, has shown promise in studies involving vitamin B6 supplementation. Understanding the metabolic conversion of these vitamers is essential for developing effective therapeutic strategies for nerve-related disorders. In this context, we will introduce a key form of vitamin B6 – Pyridoxal.
**Definition**
Pyridoxal is a human endogenous metabolite and a primary form of vitamin B6 with a molecular weight of 167.16 and the Pyridoxal Formula C8H9NO3.
**Mechanism of Action**
According to the Pyridoxal description, this compound serves as a precursor that is phosphorylated by pyridoxal kinase to form pyridoxal phosphate. In the liver, pyridoxal is oxidized to 4-pyridoxic acid, which is subsequently excreted in the urine. This metabolic pathway is central to the Pyridoxal biological activity, ensuring the availability of active cofactors required for various cellular processes.
**In Vitro Studies**
Experimental data regarding Pyridoxal In Vitro have demonstrated its influence on enzymatic activity. Specifically, Pyridoxal at a concentration of 5 μM has been shown to have an increasing effect on the activity of tyrosine decarboxylase. These findings highlight its potential role in modulating neurotransmitter synthesis and metabolic flux. While further research is ongoing to establish a comprehensive Pyridoxal protocol for various cell lines, current data support its utility as a biochemical tool in neuroprotection and metabolic research. In conclusion, Pyridoxal is a neuroprotectant and an essential vitamin B6 metabolite with potential applications in the study of carpal tunnel syndrome.
Keywords
Pyridoxal, 66-72-8, Pyridoxaldehyde, Endogenous Metabolite, Pyridoxal phosphate, 4-Pyridoxic acid, vitamin, Inhibitor, inhibitor, inhibit
References
[1] Vrolijk MF, et al. The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function. Toxicol In Vitro. 2017 Oct;44:206-212.
[2] Aufiero E, et al. Pyridoxine hydrochloride treatment of carpal tunnel syndrome: a review. Nutr Rev. 2004 Mar;62(3):96-104.
[3] Nagata, Yoshiko, Reiko Yoda, and Yoshikazu Matsushima. “Solvolysis of pyridoxal hydrochloride in alcohols.” Chemical and pharmaceutical bulletin 41.6 (1993): 1019-1022.
[4] Vrolijk, Misha F., et al. “The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function.” Toxicology In Vitro 44 (2017): 206-212.
**Background**
Cardiac arrhythmias and neuropathic pain are complex conditions often associated with the dysfunction of ion channels. Sodium channels play a critical role in the initiation and propagation of action potentials in excitable cells, including neurons and cardiomyocytes. Aberrant sodium channel activity can lead to cardiac instability, myotonia, and chronic pain syndromes, such as those induced by chemotherapy. Consequently, the modulation of these channels is a primary therapeutic strategy for managing these disorders. In this context, we will introduce an orally effective antiarrhythmic and analgesic agent – Mexiletine.
**Definition**
Mexiletine is a sodium channel blocker used for cardiovascular and neurological research, exhibiting an IC50 of 75±8 μM for tonic block and 23.6±2.8 μM for use-dependent block.
**In Vitro and In Vivo Studies**
According to the Mexiletine description, this compound is effective for treating myotonia and neuropathic pain in addition to its antiarrhythmic properties. Regarding Mexiletine in vitro activity, studies using HEK293A cells transfected with SCN5A-WT or SCN5A-1795insD demonstrated that Mexiletine (10 μM, 48 h) increases peak I Na and late I Na, while a shorter exposure (10 μM, 5 min) blocks the late I Na.
Further evaluation of Mexiletine In Vivo efficacy was conducted using male Sprague-Dawley rats with oxaliplatin-induced neuropathic pain. In this model, oxaliplatin (4 mg/kg) was administered via intraperitoneal injection on days 1, 2, 8, 9, 15, 16, 22, and 23. Acute oral administration of Mexiletine (30, 100 mg/kg, p.o.) was then used to assess the reversal of symptoms. The results indicated that 100 mg/kg completely reversed the reduction of the 50% paw withdrawal threshold in the von Frey test and the increase in withdrawal responses in the acetone test 60 to 120 minutes post-administration. A dose of 30 mg/kg provided partial reversal, while 10 mg/kg showed no significant effect. The therapeutic effect typically disappeared by 180 minutes. For researchers requiring specific Mexiletine technical information, these results highlight its potential in modulating sodium-channel-dependent pain. In conclusion, Mexiletine is a potent sodium channel blocker with significant applications in cardiovascular and neurological research.
Keywords
Mexiletine, 5370-01-4, KOE-1173, KOE1173, KOE 1173, Sodium Channel, Na channels, Na+ channels, antiarrhythmic, Class IB, myocardial, ischemia, myotonia, neuropathic pain, sodium channel, cardiovascular, neurological, HEK293A, hiPSC-CMs, Sprague-Dawley rats, Inhibitor, inhibitor, inhibit
References
[1] Campbell RW, et al. Mexiletine. N Engl J Med. 1987，316(1):29-34.
[2] De Bellis M, et al. Combined modifications of mexiletine pharmacophores for new lead blockers of Na(v)1.4 channels. Biophys J. 2013，104(2):344-54.
[3] Nasilli G, et al. Mexiletine reverses oxaliplatin-induced neuropathic pain in rats. J Pharmacol Sci. 2010;112(4):473-6.
[4] Egashira N, et al. Mexiletine reverses oxaliplatin-induced neuropathic pain in rats. J Pharmacol Sci. 2010，112(4):473-6.
**Background**
Casein Kinase II (CKII) is a ubiquitous serine/threonine kinase that plays a critical role in various cellular processes, including signal transduction, cell cycle regulation, and apoptosis. Due to its involvement in multiple oncogenic pathways, CKII has become a significant target in cancer research. Beyond oncology, the regulation of CKII is essential for the maintenance and differentiation of epithelial cells. In the skin, the precise control of keratinocyte differentiation is vital for the formation of the epidermal barrier and the healing of cutaneous wounds. Dysregulation of this process can lead to various skin disorders. Therefore, identifying small molecules that can modulate this pathway is of great research importance. In this context, we will introduce a potent CKII inhibitor – Casein Kinase II Inhibitor IV.
**Definition**
Casein Kinase II Inhibitor IV is a potent, ATP-competitive inhibitor of casein kinase II with an IC50 value of 9 nM. According to the Casein Kinase II Inhibitor IV description, this compound also functions as an inducer of differentiation in human keratinocytes.
**In Vitro Studies**
The Casein Kinase II Inhibitor IV biological activity has been extensively evaluated in human epidermal keratinocytes (NHEKs). In vitro studies demonstrate that treatment of NHEKs with Casein Kinase II Inhibitor IV leads to a significant increase in early differentiation markers, specifically keratins 1 and 10, within 48 hours. Furthermore, increased levels of involucrin (IVL) and transglutaminase (TGM) are observed at 72 hours and persist through 96 hours. At later time points, treated cells express loricrin, a marker of terminal differentiation. These findings are supported by messenger RNA (mRNA) expression analysis, which shows that at early time points (12 and 24 h), the inhibitor induces a 5.4-fold upregulation of both keratin 1 and keratin 10. At later time points (36 and 48 h), terminal differentiation marker genes are significantly upregulated, including filaggrin (5.6-fold), TGM 1 (4.8-fold), loricrin (3.3-fold), and IVL (1.8-fold). For researchers seeking detailed Casein Kinase II Inhibitor IV technical information, these results consistently highlight the ability of the compound to induce the differentiation of epidermal progenitor cells into terminally differentiated keratinocytes. In conclusion, Casein Kinase II Inhibitor IV is a potent CKII inhibitor and a small-molecule inducer of epidermal keratinocyte differentiation.
Keywords
Casein Kinase II Inhibitor IV, 863598-09-8, Casein Kinase, Inhibitor, inhibitor, inhibit
References