colonic

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

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

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.

Dextran sulfate sodium salt (MW 36,000–50,000) is a medium molecular weight polyanionic dextran derivative with strong intestinal epithelial permeability. It is the most commonly used agent for inducing inflammatory bowel disease (IBD) models, effectively inducing both acute and chronic colitis. Its mechanism may involve macrophage dysfunction and gut microbiota dysbiosis. Due to its colonic epithelial toxicity, long-term use can also induce colorectal cancer models.

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.

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.

A-1211212 (BCL2-IN-1) is a potent and selective Bcl-2 inhibitor. It promotes lymphocyte apoptosis, alters colonic mucosa in mice, and improves inflammation.

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

X-17 is a potent Vanin-1 inhibitor known for its anti-inflammatory and antioxidant properties. It reduces the expression of inflammatory factors and inhibits myeloperoxidase activity, while enhancing colonic glutathione reserves and restoring the intestinal barrier.

5-HT4R agonist-2 (Compound 4) is a selective 5-HT4 receptor agonist with an EC50 of 0.41 nM. This compound significantly enhances intestinal and colonic transit, increases stool output and moisture content, while maintaining minimal systemic absorption, making it a promising candidate for research in chronic idiopathic constipation.

ATB-429 is a mesalazine derivative capable of releasing H2S, demonstrating significant analgesic and anti-inflammatory effects in an irritable bowel syndrome (IBS) model. By releasing hydrogen sulfide (H2S), ATB-429 modulates hypersensitivity induced by colorectal distension in healthy and post-colitis rats. It alleviates abdominal withdrawal responses and inhibits spinal c-Fos mRNA expression, indicating its potential to relieve pain associated with gastrointestinal inflammation. Furthermore, ATB-429 downregulates mRNA expression of colonic cyclooxygenase-2 (COX-2) and IL-1β, an effect not observed with mesalazine alone. The mechanism involves ATP-sensitive K+ (KATP) channels, evidenced by the reversal of ATB-429's effects with glibenclamide. These findings suggest that ATB-429 may offer therapeutic benefits for treating inflammatory pain-related bowel conditions.

SKF38393 hydrobromide is the salt form of SKF38393.SKF38393 is a dopamine D1 receptor agonist that increases the expression of Shati/Nat8L mRNA in the NAc of mice; increases the frequency of 5-hydroxytryptamine and n -methyl- D -aspartate-induced locomotion-associated ruptures in astrocytes; can mimic the dopamine-induced inhibition of colonic motility in mice; can promote locust swarming

NSC61610 is a molecule with anti-inflammatory effects that activates PPARγ in vitro via LANCL2 and adenylate cyclase/cAMP-dependent pathways, downregulates colonic inflammatory gene expression, and promotes regulatory T cell responses, thereby improving experimental colitis.

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

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

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

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

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

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

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).

Theaflavin digallate and lactic acid together could reduce herpes simplex virus transmission.

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.

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.

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.