β-glucuronidase

β-Glucuronidase-IN-1 is an E. coli β-glucuronidase (β-glucuronidase) inhibitor with a potent, selective, non-competitive, and orally active IC50 and Ki value of 283 nM and 164 nM, respectively, against E. coli β-glucuronidase.

2,2'-Dihydroxy chalcone is a potent inhibitor of β-glucuronidase (IC50=1.6±0.2 μM) and lysozyme (IC50=1.4±0.2 μM) release from rat neutrophils stimulated with fMLP CB.2,2'-Dihydroxy chalcone has inhibitory activity against Escherichia coli, Shigella fowleri, Staphylococcus albicans and Staphylococcus aureus.

β-Glucuronidase-IN-3 (Compound 49) is a covalent allosteric inhibitor targeting β-glucuronidase. It exhibits potent inhibitory activity against Escherichia coli β-glucuronidase (EcGUS) with an IC50 of 12.9 nM. The compound exerts its inhibitory effect through reversible covalent modification of cysteine residues (Cys28, Cys443, and Cys197) on EcGUS. It is applicable in research on gut microbiota-related diseases, particularly in reducing the toxic side effects of Irinotecan and non-steroidal anti-inflammatory drugs (NSAIDs).

β-Glucuronidase-responsive conjugate 1 (compound 3) is a well-balanced photosensitizer with photodynamic activity. It effectively inhibits the viability and growth of T-24 cells, with an IC50 of 0.2 μM, and is applicable for bladder cancer research.

D-Saccharic acid 1,4-lactone hydrate is a potent β-glucuronidase inhibitor (IC50=48.4 μM) that possesses anticarcinogenic, detoxifying, and antioxidant properties[1][2].

β-Glucuronidase-IN-2 is a potent inhibitor of E. coli β-glucuronidase [IC50: 0.24 μM, Ki: 1.09 μM] and exhibits anti-proliferative effects with potential for anti-cancer and anti-inflammatory therapeutic studies.

β-Glucuronidase/hCAII-IN-2 is a potent inhibitor of β-glucuronidase and hCA II, and their IC50 values were 670.7 μM and 21.77 μM, respectively.

β-Glucuronidase/hCAII-IN-2 (Compound 12e) effectively inhibits β-glucuronidase and human Carbonic Anhydrase II (hCA II) with IC50 values of 440.1 μM and 4.91 μM, respectively [1].

Ganoderenic acid A has a potent hepatoprotective, and cytotoxic effects, it shows inhibitory activity on human aldose reductase in vitro.

EHT 1610 (EHT 5372) is a potent inhibitor of DYRK, with an IC50 of 0.36 nM and 0.59 nM for DYRK1A and DYRK1B, respectively. EHT 1610 has an inhibitory effect on leukemia, regulating cell cycle and inducing cell apoptosis.

GSK-626616 is a potent and orally bioavailable DYRK3 inhibitor (IC50: 0.7 nM). It inhibits other members of the DYRK family with similar potency. GSK-626616 is a potential therapy for the treatment of anemia.

6-Chloro-3-indolyl-β-D-Glucuronide (cyclohexylammonium salt) is a chromogenic substrate for β-glucuronidase and can be utilized in the histochemical analysis of β-glucuronidase activity.

(+)-Guaiacin, isolated from the bark of Machilus wangchiana Chun, demonstrates potent in vitro inhibition of β-glucuronidase release in rat polymorphonuclear leukocytes (PMNs) induced by platelet-activating factor (PAF).

EcGUS-IN-1 (Compound E-9) is a non-competitive inhibitor of β-glucuronidase, featuring an IC50 value of 2.68 μM and a Ki value of 1.64 μM. This compound effectively mitigates gastrointestinal adverse events (GIAE) associated with Escherichia coli infections by inhibiting the activity of E. coli β-glucuronidase.

Saccharic acid serves as a competitive inhibitor of β-glucuronidase. It significantly slows down the hydrolysis of l-ortho-hydroxyphenylazo-2-naph-thol glucuronide in frozen-thawed mouse kidney slices, yet it does not impact liver regeneration following injury or the growth of infant mice.

β-Glu-PAB(CH2NH2)-Exatecan (Compound 9a) is an inhibitor of topoisomerase I. It binds to the topoisomerase I-DNA complex, preventing the re-ligation of DNA strands, leading to DNA breaks and apoptosis. In the tumor microenvironment, where β-glucuronidase is highly expressed, β-Glu-PAB(CH2NH2)-Exatecan is specifically cleaved to release Exatecan, which then exerts its cytotoxic effects. Additionally, β-Glu-PAB(CH2NH2)-Exatecan serves as an intermediate for the synthesis of Mal((3S,3aR,6S,6aR)-Hexahydrofuro[3,2-b]furan-3,6-diamine-PEG12)-β-Glu-PAB-Exatecan. This compound holds potential for cancer research.

Protein tyrosine phosphatases (PTPs) remove phosphate from tyrosine residues of cellular proteins. Reversible phosphorylation catalyzed by the coordinated actions of protein tyrosine kinases and phosphatases is key to the regulation of the signaling events that control cell growth and proliferation, differentiation, and survival or apoptosis, as well as adhesion and motility. RK-682, a bioactive compound originally isolated from the fermentation of Streptomyces sp. 88-682, is an inhibitor of the PTPs. It inhibits the phosphorylation of CD45 and VHR with IC50 values of 54 and 2 μM, respectively, and arrests cell cycle progress at the G1/S transition. It is also reported to inhibit heparanase (IC50 = 17 μM), an endo-β-D-glucuronidase involved in tumor cell invasion and angiogenesis. RK-682 (calcium salt) is a less soluble version of the free acid.

Antileukinate is a synthetic hexapeptide with an acetylated amino terminus and an amidated carboxyl terminus that inhibits the binding of CXC chemokines to the chemokine receptor CXCR2. It inhibits IL-8 binding to neutrophils (Ki = 2.7-13 μM), prevents neutrophil chemotaxis and β-glucuronidase release, and blocks IL-8-induced skin edema in rabbits. At 53 mg/kg, antileukinate has been shown to protect mice against acute pancreatitis and associated lung injury.

hCAII-IN-4 (Compound 12j) is a potent inhibitor of human carbonic anhydrase II (hCA II) with an IC50 of 7.78 μM, and also inhibits β-glucuronidase with an IC50 of 773.9 μM [1].

3-Chlorogentisyl alcohol, characterized by its potent inhibitory action against E. coli β-glucuronidase with an IC(50) value of 0.74 µM and a K(i) value of 0.58 µM, demonstrates significant antiproliferative activity. This compound shows promise for use in the research of anti-cancer and anti-inflammatory therapies.

DMAT (Casein kinase II Inhibitor) is a potent and specific inhibitor of CK2(IC50 value of 130 nM).

β-Glucuronide-NB-bis[N(Me)-methyl ester]-MMAE (compound 20), an auristatins-glucuronide conjugate, exhibits in vitro antiproliferative effects on cancer cells, both β-glucuronidase pretreated and untreated, with an IC50 range of 5.7 nM to 9.7 nM. Demonstrating powerful antitumor efficacy in an HCT-116 xenograft mouse model, this compound does not induce side effects [1].

HPSE1-IN-1 (compound 16) functions as a selective Heparanase-1 (HPSE1) inhibitor, displaying moderate activity against exo-β-d-glucuronidase (GUSβ) and glucocerebrosidase (GBA) [1].

HPSE1-IN-2 (compound 2) functions as an inhibitor of Heparanase-1 (HPSE1) while concurrently inhibiting exo-β-d-glucuronidase (GUSβ) and glucocerebrosidase (GBA) activities [1].