|
Glaucoma
|
0.070 |
Biomarker
|
disease |
BEFREE |
The obtained 1,3-diaryltriazene-substituted sulfonamides were investigated as inhibitors of four selected human carbonic anhydrase (CA, EC 4.2.1.1) isoforms (hCA I, hCA II, hCA VII and hCA IX) are involved in various diseases such as glaucoma, epilepsy, retinitis pigmentosa, cancer, obesity, etc.
|
29462772 |
2018 |
|
Glaucoma
|
0.070 |
Biomarker
|
disease |
BEFREE |
The physiologically important and off-target cytosolic isoform hCA I was weakly inhibited by most of the newly synthesized sulfonamides while the glaucoma associated isoform hCA II was moderately inhibited with K<sub>I</sub>s spanning in low nanomolar range (K<sub>I</sub> = 8.0 nM-0.903 μM).
|
31539777 |
2019 |
|
Glaucoma
|
0.070 |
Biomarker
|
disease |
BEFREE |
The cytosolic isoform hCA I was inhibited with K<sub>i</sub>'s ranging between 53.2 nM and 7.616 μM whereas the glaucoma associated cytosolic isoform hCA II was inhibited with K<sub>i</sub>'s in the range 21.8 nM-0.807 μM.
|
29571155 |
2018 |
|
Glaucoma
|
0.070 |
Biomarker
|
disease |
BEFREE |
Most of these compounds exhibited excellent activity against all these isoforms. hCA I was inhibited with <i>K<sub>i</sub></i>s in the range of 50.8-966.8 nM, while the glaucoma associated hCA II was inhibited with <i>K<sub>i</sub></i>s in the range of 6.5-760.0 nM.
|
31237458 |
2019 |
|
Glaucoma
|
0.070 |
Biomarker
|
disease |
BEFREE |
These compounds were tested for the inhibition of four human (h) isoforms, hCA I, II, IX, and XII, involved in pathologies such as glaucoma (CA II and XII) or cancer (CA IX/XII).
|
31112841 |
2019 |
|
Glaucoma
|
0.070 |
Biomarker
|
disease |
BEFREE |
The ureido benzenesulfonamides incorporating triazinyl moieties were investigated as inhibitors of four selected physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, namely, hCA I, II, IX, and XII which are involved in various diseases such as glaucoma, epilepsy, obesity and cancer.
|
30312866 |
2019 |
|
Glaucoma
|
0.070 |
Biomarker
|
disease |
BEFREE |
Some of these sulfonamides showed effective inhibitory action (in the nanomolar range) against the cytosolic isoform hCA II and the transmembrane, tumor-associated one hCA IX, making them interesting candidates for preclinical evaluation in glaucoma or various tumors in which the two enzymes are involved. hCA I and IV were on the other hand less inhibited by these sulfonamides, with inhibition constants in the micromolar range.
|
28161252 |
2017 |
|
Epilepsy
|
0.030 |
Biomarker
|
disease |
BEFREE |
Most screened sulfonamides showed high potency in inhibiting hCA II, widely involved in glaucoma, epilepsy, edema, and other pathologies (K<sub>i</sub>s in the ranging from 6.32 ± 0.06 to 128.93 ± 23.11 nM). hCA I was inhibited with K<sub>i</sub>s in the range of 6.80 ± 0.10-85.91 ± 7.57 nM, whereas AChE in the range of 60.79 ± 3.51-249.55 ± 7.89 nM.
|
31129502 |
2019 |
|
Epilepsy
|
0.030 |
Biomarker
|
disease |
BEFREE |
Thus, HCAR1 represents a novel therapeutic target for pathologies characterized by network hyperexcitability dysfunction, such as epilepsy.
|
30926749 |
2019 |
|
Epilepsy
|
0.030 |
Biomarker
|
disease |
BEFREE |
The ureido benzenesulfonamides incorporating triazinyl moieties were investigated as inhibitors of four selected physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, namely, hCA I, II, IX, and XII which are involved in various diseases such as glaucoma, epilepsy, obesity and cancer.
|
30312866 |
2019 |
|
Malignant neoplasm of breast
|
0.020 |
Biomarker
|
disease |
BEFREE |
Recently, hydroxycarboxylic acid receptor 1 (HCAR1) was shown to drive lactate-dependent enhancement of cell survival and metastasis in pancreatic and breast cancers.
|
28258841 |
2017 |
|
Malignant neoplasm of breast
|
0.020 |
Biomarker
|
disease |
BEFREE |
Overall, these findings identify GPR81 as a tumor-promoting receptor in breast cancer progression and suggest a novel mechanism that regulates GPR81-dependent activation of the PI3K/Akt signaling axis in tumor microenvironment.
|
27765922 |
2016 |
|
Alzheimer's Disease
|
0.010 |
Biomarker
|
disease |
BEFREE |
As a result, the novel menthol sulfamate and menthol carbonyl sulfamate derivatives can be promising Alzheimer's disease drug candidates and novel hCA I and hCA II enzymes inhibitors.
|
30255953 |
2018 |
|
Amyotrophic Lateral Sclerosis
|
0.010 |
Biomarker
|
disease |
BEFREE |
As the physiological function hCA I is poorly understood, and it was recently shown to be involved in the pathogenesis of cerebral malaria and amyotrophic lateral sclerosis, selective and effective inhibitors may be useful as tools or drugs for better understanding this abundant isoform.
|
28318894 |
2017 |
|
Diabetes
|
0.010 |
AlteredExpression
|
disease |
BEFREE |
Potentially novel GPR81 agonists were identified that suppressed fasting plasma free fatty acid levels in rodents and in addition improved insulin sensitivity in mouse models of insulin resistance and diabetes.
|
28978803 |
2017 |
|
Obesity
|
0.010 |
Biomarker
|
disease |
BEFREE |
The ureido benzenesulfonamides incorporating triazinyl moieties were investigated as inhibitors of four selected physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, namely, hCA I, II, IX, and XII which are involved in various diseases such as glaucoma, epilepsy, obesity and cancer.
|
30312866 |
2019 |
|
Pancreatic carcinoma
|
0.010 |
AlteredExpression
|
disease |
BEFREE |
In vivo, GPR81 expression levels correlated with the rate of pancreatic cancer tumor growth and metastasis.
|
24928781 |
2014 |
|
Impaired cognition
|
0.010 |
Biomarker
|
disease |
BEFREE |
We suggest that G protein-coupled receptor 81 mediates cognitive decline in the diabetic rat.
|
30171160 |
2018 |
|
Malignant neoplasm of pancreas
|
0.010 |
AlteredExpression
|
disease |
BEFREE |
In vivo, GPR81 expression levels correlated with the rate of pancreatic cancer tumor growth and metastasis.
|
24928781 |
2014 |
|
Nijmegen Breakage Syndrome
|
0.010 |
AlteredExpression
|
disease |
BEFREE |
We observed that the HCAR1 agonist dihydroxybenzoic acid (DHBA) up-regulated BRCA1 (breast cancer type 1 susceptibility protein) and NBS1 (Nijmegen breakage syndrome 1) expression in HeLa cells.
|
28258841 |
2017 |
|
Breast Carcinoma
|
0.010 |
Biomarker
|
disease |
BEFREE |
Overall, these findings identify GPR81 as a tumor-promoting receptor in breast cancer progression and suggest a novel mechanism that regulates GPR81-dependent activation of the PI3K/Akt signaling axis in tumor microenvironment.
|
27765922 |
2016 |
|
Colon Carcinoma
|
0.010 |
Biomarker
|
disease |
BEFREE |
To elucidate the mechanism of NMF-mediated radiosensitization, we examined the effects of this agent on gamma-ray-induced DNA double-strand breaks and micronuclei in two cell lines, clone A (human colon carcinoma) and HCA-1 (murine hepatocarcinoma).
|
2756107 |
1989 |
|
hepatitis immune
|
0.010 |
Biomarker
|
disease |
BEFREE |
The administration of lactate reduced inflammation and organ injury in mice with immune hepatitis; this reduction required Gpr81 dependence in vivo.
|
24657625 |
2014 |
|
Liver carcinoma
|
0.010 |
Biomarker
|
disease |
BEFREE |
To elucidate the mechanism of NMF-mediated radiosensitization, we examined the effects of this agent on gamma-ray-induced DNA double-strand breaks and micronuclei in two cell lines, clone A (human colon carcinoma) and HCA-1 (murine hepatocarcinoma).
|
2756107 |
1989 |
|
Autosomal Recessive Osteopetrosis
|
0.010 |
Biomarker
|
disease |
BEFREE |
Red cell carbonic anhydrase isoenzyme activities (HCA-I and HCA-II) were quantitated in blood hemolysates of two female siblings affected with autosomal recessive osteopetrosis in addition to family members who were both obligate and potential heterozygotes as well as normal controls.
|
3933860 |
1985 |