colonic

Trimebutine (Mebutin) is a spasmolytic agent that regulates intestinal and colonic motility and relieves abdominal pain with antimuscarinic and weak mu-opioid agonist effects. It is marketed for the treatment of irritable bowel syndrome (IBS) and lower gastrointestinal tract motility disorders, with IBS being one of the most common multifactorial GI disorders. It is used to restore normal bowel function and is commonly present in pharmaceutical mixtures as trimebutine maleate salt form. Trimebutine is not an FDA-Approved Clinical drug, but it is available in Canada and several other international countries.

Glycoursodeoxycholic acid (Ursodeoxycholylglycine) is an acyl glycine and a bile acid-glycine conjugate. It is a secondary bile acid produced by the action of enzymes existing in the microbial flora of the colonic environment. In hepatocytes, both primary and secondary bile acids undergo amino acid conjugation at the C-24 carboxylic acid on the side chain, and almost all bile acids in the bile duct, therefore, exist in a glycine conjugated form. Bile acids are steroid acids found predominantly in bile of mammals.

P-XSC has anticancer activity, inhibits proliferation of colonic epithelial cells in patients with adenomatous polyps, and may be used in the study of breast cancer.

Quercetagitrin (Quercetagetin-7-O-glucoside), isolated from the African Marigold (Tagetes erecta), exhibits anti-inflammatory activity.

Zamifenacin fumarate (UK-76654 fumarate) is a potent, gut-selective antagonist of the muscarinic M3 receptor.

Urocortin II is a neuropeptide hormone and member of the corticotropin-releasing factor (CRF) family which includes mammalian CRF , urocortin , urocortin III , frog sauvagine, and piscine urotensin I.1 Mouse urocortin II shares 34 and 42% sequence homology with rat CRF and urocortin . It is expressed in mouse paraventricular, supraoptic, and arcuate nuclei of the hypothalamus, the locus coeruleus, and in motor nuclei of the brainstem and spinal ventral horn. Urocortin II selectively binds to CRF1 over CRF2 receptors (Kis = 0.66 and >100 nM, respectively) and induces cAMP production in CHO cells expressing CRF2 (EC50 = 0.14 nM). In vivo, urocortin II suppresses nighttime food intake by 35% in rats when administered intracerebroventricularly at a dose of 1 μg. Urocortin II (0.1 and 0.5 μg, i.c.v) stimulates fecal pellet output, increases distal colonic transit, and inhibits gastric emptying in mice.2References1. Reyes, T.M., Lewis, K., Perrin, M.H., et al. Urocortin II: A member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors. Proc. Natl. Acad. Sci. U.S.A. 98(5), 2843-2848 (2001).2. Martinez, V., Wang, L., Million, M., et al. Urocortins and the regulation of gastrointestinal motor function and visceral pain. Peptides 25(10), 1733-1744 (2004). Urocortin II is a neuropeptide hormone and member of the corticotropin-releasing factor (CRF) family which includes mammalian CRF , urocortin , urocortin III , frog sauvagine, and piscine urotensin I.1 Mouse urocortin II shares 34 and 42% sequence homology with rat CRF and urocortin . It is expressed in mouse paraventricular, supraoptic, and arcuate nuclei of the hypothalamus, the locus coeruleus, and in motor nuclei of the brainstem and spinal ventral horn. Urocortin II selectively binds to CRF1 over CRF2 receptors (Kis = 0.66 and >100 nM, respectively) and induces cAMP production in CHO cells expressing CRF2 (EC50 = 0.14 nM). In vivo, urocortin II suppresses nighttime food intake by 35% in rats when administered intracerebroventricularly at a dose of 1 μg. Urocortin II (0.1 and 0.5 μg, i.c.v) stimulates fecal pellet output, increases distal colonic transit, and inhibits gastric emptying in mice.2 References1. Reyes, T.M., Lewis, K., Perrin, M.H., et al. Urocortin II: A member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors. Proc. Natl. Acad. Sci. U.S.A. 98(5), 2843-2848 (2001).2. Martinez, V., Wang, L., Million, M., et al. Urocortins and the regulation of gastrointestinal motor function and visceral pain. Peptides 25(10), 1733-1744 (2004).

(Ala13)-Apelin-13 acetate, an APJ antagonist, modulates CRF-induced enhanced colonic motility, visceral sensation, and gut barrier.

Zamifenacin obviously decreases colonic motility in irritable bowel syndrome. Zamifenacin is an effective gut-selective muscarinic M3 receptor antagonist.

MK-8970 is an acetal carbonate prodrug of raltegravir with enhanced colonic absorption.

(S)-Elobixibat is the S-isomer of Elobixibat. It is an orally active inhibitor of Apical Sodium-Dependent Bile (IBAT) and can reduce LDL cholesterol, increase serum GLP-1, and promote colonic motility. This compound shows potential for treating metabolic syndrome and can be studied for constipation, dyslipidemia, non-alcoholic hepatitis, and liver tumors.

1. Theaflavine-3,3'-digallate (theaflavin digallate) and lactic acid together could reduce herpes simplex virus transmission.

MOMBA is a selective orthosteric agonist specifically targeting engineered human free fatty acid 2 (hFFA2) receptors, particularly those modified as designer receptors activated by designer drugs (DREADD). It demonstrates selective inactivity towards wild-type hFFA2, hFFA3, and mouse FFA2 receptors. It efficiently inhibits forskolin-induced cAMP levels in cells equipped with the hFFA2-DREADD receptor, exhibiting enhanced potency and comparable efficacy to Sorbic acid. In transgenic mice containing the hFFA2-DREADD gene, MOMBA administration notably slows gut transit and facilitates a concentration-dependent enhancement of GLP-1 secretion from colonic crypts, all while being orally bioavailable.

Aloe emodin anthrone is a stimulant-laxative which has been shown to enhance colonic membrane permeability of water-soluble and poorly permeable compounds.

Kobusin, a Calmodulin inhibitor, shows mild antiplasmodial,anti-inflammatory, and cytotoxic activities; it may be beneficial for the treatment of neuro-inflammatory diseases through the inhibition of iNOS expression and peroxynitrite scavenging potential. Kobusin can mildly reduce gastrointestinal motility in mice, it activates CFTR and CaCCgie chloride channel activities in mouse colonic epithelia and shows inhibitory effects toward ANO1 CaCC-mediated short-circuit currents in ANO1 CaCC-expressing FRT cells.

Urocortin III (mouse) (free acid), a selective high-affinity agonist for the CRF2 receptor, significantly inhibits gastric emptying without affecting colonic transit [1] [2].

Taurohyodeoxycholic acid (THDCA) is a taurine-conjugated form of the secondary bile acid hyodeoxycholic acid .1THDCA decreases the size and weight of human gallstonesin vitro. It increases bile flow, biliary cholesterol secretion, and biliary lipid secretion in rats.2Co-administration of THDCA with taurochenodeoxycholic acid prevents TCDCA-induced hepatotoxicity, increasing bile flow as well as biliary acid and phospholipid secretion in rats.3THDCA also reduces myeloperoxidase activity, expression of TNF-α and IL-6, and colonic damage in a mouse model of TNBS-induced ulcerative colitis.4Taurohyodeoxycholic acid MaxSpec standard is a quantitative grade standard of taurohyodeoxycholic acid (sodium salt) that has been prepared specifically for mass spectrometry and related applications where quantitative reproducibility is required. The solution has been prepared gravimetrically and is supplied in a deactivated glass ampule sealed under argon. The concentration was verified by comparison to an independently prepared calibration standard. Verified concentration is provided on the certificate of analysis. This taurohyodeoxycholic acid MaxSpec standard is guaranteed to meet identity, purity, stability, and concentration specifications and is provided with a batch-specific certificate of analysis. Ongoing stability testing is performed to ensure the concentration remains accurate throughout the shelf life of the product.Note: The amount of solution added to the vial is in excess of the listed amount. Therefore, it is necessary to accurately measure volumes for preparation of calibration standards. Follow recommended storage and handling conditions to maintain product quality.

Lafutidine (FRG-8813) is a newly developed histamine H2-receptor antagonist that inhibits gastric acid secretion.

Des-4-fluorobenzyl Mosapride, the main metabolite of mosapride, acts as a gastroprokinetic agent improving upper gastrointestinal (GI) motility by stimulating the serotonin receptor 4 (5-HT4; EC50= 74.2 nM, in guinea pig ileal longitudinal muscle myenteric plexus). It has been shown to increase colonic motility in dogs, horses, and guinea pigs in vivo. Mosapride, including this metabolite, is utilized in human and veterinary medicine to mitigate post-surgical and Parkinson's-induced constipation.

α-CGRP (mouse, rat) TFA, a neuropeptide belonging to the calcitonin gene-related peptide (CGRP) family, is predominantly located at neuromuscular junctions and functions as a potent vasodilator. Peripheral administration of α-CGRP (mouse, rat) TFA may result in decreased blood pressure and elevated heart rate, in addition to the relaxation of colonic smooth muscle. This compound shows promising utility in the investigation of cardiovascular, pro-inflammatory, migraine, and metabolic conditions [1] [2] [3].

Aloe-emodin-glucoside is a stimulant-laxative which has been shown to enhance colonic membrane permeability of water-soluble and poorly permeable compounds.

Glycoursodeoxycholic Acid-d4 is a deuterated compound of Glycoursodeoxycholic Acid. Glycoursodeoxycholic Acid has a CAS number of 64480-66-6. Glycoursodeoxycholic acid is an acyl glycine and a bile acid-glycine conjugate. It is a secondary bile acid produced by the action of enzymes existing in the microbial flora of the colonic environment. In hepatocytes, both primary and secondary bile acids undergo amino acid conjugation at the C-24 carboxylic acid on the side chain, and almost all bile acids in the bile duct, therefore, exist in a glycine conjugated form. Bile acids are steroid acids found predominantly in bile of mammals.

The mechanism by which Glycodeoxycholate Sodium induces apoptosis in hepatocytes is related to DNA cleavage by endonucleases. It is a secondary bile acid produced by the action of enzymes present in the microflora of the colonic environment.

Wnt signaling is required for direct multiple biological processes and also plays key roles in the pathogenesis of various diseases. Cyclic AMP response element-binding protein (CREB) is a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds as a homodimer to the cAMP-responsive element, an octameric palindrome. The protein is phosphorylated by several protein kinases, and induces transcription of genes in response to hormonal stimulation of the cAMP pathway. Via generating a transcriptionally active complex with β-catenin, CREB acts as a mediator of Wnt signaling.ICG-001 is an inhibitor of β-catenin/CREB mediated transcription. The direct cellular target of ICG-001 is CREB. the inhibitory IC50of ICG-001 against β-catenin/CREB mediated transcription was 3 μM. ICG-001 treatment at the concentration of 25 μM for 24h significantly increased caspase activity in both colon cancer cell lines SW480 and HCT116 cell lines but not in normal colonic epithelial cells CCD-841Co. In a cell growth inhibition assay, the IC50s of ICG-001 against SW480 and HCT116 cells were 4.43 μM and 5.95 μM, respectively.In a SW620 nude mouse xenograft model, an water-soluble analog of ICG-001 given at the dose of 150 mg/kg i.v. once in every 2 days dramatically suppressed tumor growth. In a bleomycin-induced pulmonary fibrosis mice model, ICG-001 given at the dose of 5 mg/kg per day reversed pulmonary fibrosis. In a rat myocardial infarction model, ICG-001 was administrated subcutaneously at the dose of 50 mg/kg/day for 10 days which significantly improved cardiac contractile function after myocardial infarction in the rats.

N-acetyl-5-Aminosalicylic acid is a metabolite of the anti-inflammatory agent 5-aminosalicylic acid and its prodrug form, sulfasalazine . It is formed in the liver, intestinal lumen, and colonic epithelial cells via N-acetyltransferases. It reduces IFN-γ binding to colonic epithelial cells by 24% when used at a concentration of 10 mM. N-acetyl-5-Aminosalicylic acid (100 μM) scavenges 2,2-diphenyl-1-picrylhydrazyl radicals in a cell-free assay and inhibits base hydroxylation in DNA stimulated by hydroxy radicals. Unlike sulfasalazine, N-acetyl-5-aminosalicylic acid does not inhibit 15-hydroxy prostaglandin dehydrogenase (PGDH). Urinary levels of N-acetyl-5-aminosalicylic acid have been used as a marker of 5-ASA adherence in patients with inflammatory bowel disease.

Succinic acid sodium is an orally active anxiolytic. Succinic acid sodium down-regulates the expression of KCNMB1 (potassium channel subunit β1) and TET1 (10-11 translocation 1). succinic acid sodium inhibits the proliferation of colonic epithelial cells in vivo. Succinic acid sodium can be used to study hypertension in pregnancy.

STA 2 is an analogue of TXA2, a thromboxane receptor in the colonic epithelium.

Butyrylcholine is a novel colonic ion transport regulator produced by colonic epithelial cells that stimulates nicotine and muscarinic receptors.

DRAinh-A250 is a SLC26A3 inhibitor which blocks colonic fluid absorption and reduces constipation.

Ciclotropium (free base) is quaternary ammonium compound with anticholinergic and parasympatholytic activity. Oral Cyclotropium bromide inhibited fasting and meal-stimulated colonic motility significantly without causing adverse side effects. After cyclotropium bromide, there was a significant correlation between antral contraction amplitude and gastric emptying.

13,14-Dihydro-15-keto prostaglandin D2 (DK-PGD2), a PGD2 metabolite formed by the 15-hydroxyl PGDH pathway, is a selective agonist for the DP2 receptor and can inhibit ion flux in canine colonic mucosa preparation [1].