|
Primary malignant neoplasm
|
0.050 |
Biomarker
|
group |
BEFREE |
As such, these three metabolite receptors play a critical role in cancer and represent a new class of drug targets with selective antagonists of GPR81 and GPR91 for cancer treatment and agonists of GPR109A for cancer prevention.
|
28512002 |
2017 |
|
Malignant Neoplasms
|
0.050 |
Biomarker
|
group |
BEFREE |
GPR81 is a lactate receptor recently identified in adipose and muscle cells that has not been investigated in cancer.
|
24928781 |
2014 |
|
Neoplasm Metastasis
|
0.050 |
Biomarker
|
phenotype |
BEFREE |
Cells in which GPR81 was silenced showed a dramatic decrease in growth and metastasis.
|
24928781 |
2014 |
|
Primary malignant neoplasm
|
0.050 |
Biomarker
|
group |
BEFREE |
GPR81 is a lactate receptor recently identified in adipose and muscle cells that has not been investigated in cancer.
|
24928781 |
2014 |
|
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 |
|
Tumor Progression
|
0.010 |
AlteredExpression
|
phenotype |
BEFREE |
These findings shed light on the transcriptional mechanism by which GPR81 expression is regulated in cancer cells, and provides mechanistic insight into how aberrant signaling and continually high lactate levels due to metabolic switch may yield a feed-forward/self-enabling loop to promote tumor progression.
|
31666207 |
2020 |
|
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 |
|
Retinal Diseases
|
0.010 |
Biomarker
|
group |
BEFREE |
Herein, we show that GPR81, localized predominantly in Müller cells, governs deep vascular complex formation during development and in ischemic retinopathy.
|
31220454 |
2019 |
|
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 |
|
Mental deterioration
|
0.010 |
Biomarker
|
phenotype |
BEFREE |
We suggest that G protein-coupled receptor 81 mediates cognitive decline in the diabetic rat.
|
30171160 |
2018 |
|
Impaired cognition
|
0.010 |
Biomarker
|
disease |
BEFREE |
We suggest that G protein-coupled receptor 81 mediates cognitive decline in the diabetic rat.
|
30171160 |
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 |
|
Diabetes Mellitus
|
0.010 |
AlteredExpression
|
group |
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 |
|
Disorder of eye
|
0.010 |
Biomarker
|
group |
BEFREE |
Interesting inhibitory activities were observed against all these isoforms. hCA I, an isoform involved in several eye diseases was inhibited moderately with K<sub>I</sub>s in the range of 191.8-904.2 nM, hCA II, an antiglaucoma drug target was highly inhibited by the new sulfonamides, with K<sub>I</sub>s in the range of 0.75-8.8 nM. hCA IX, a tumor-associated isoform involved in cancer progression and metastatic spread was potently inhibited by the new sulfonamides, with K<sub>I</sub>s in the range of 2.3-87.3 nM, whereas hCA XII, and antiglaucoma and anticancer drug target, was inhibited with K<sub>I</sub>s in the range of 6.1-71.8 nM.
|
28965419 |
2017 |
|
Hypertensive disease
|
0.010 |
Biomarker
|
group |
BEFREE |
Unexpectedly, the agonists simultaneously induced hypertension in rodents, including wild-type, but not GPR81-deficient mice.
|
28978803 |
2017 |
|
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 |
|
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 |
|
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 |
|
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 |