Anyone been prescribed this for OLP? It's a spray to use on the sores in the mouth, prescribed by my doctor.
I couldn't find any other mention of it in this sub, so putting it there for anyone else if they may find it useful. It's supposed to help wounds heal quicker.
Current approved FGFR inhibitors lack selectivity within the FGFR family, which may contribute to their poor tolerability. Here, we describe DGY-09-192, a selective FGFR1&2 degrader that destabilized wildtype FGFR1&2 and FGFR2 fusion proteins, had potent anti-proliferative activity in FGFR2-dependent cells, and possessed pharmacokinetics properties suitable for in vivo degradation. Thus, FGFR degradation may be a promising therapeutic approach.
Abstract
Aberrant activation of FGFR signaling occurs in many cancers, and ATP-competitive FGFR inhibitors have received regulatory approval. Despite demonstrating clinical efficacy, these inhibitors exhibit dose-limiting toxicity, potentially due to a lack of selectivity amongst the FGFR family and are poorly tolerated. Here, we report the discovery and characterization of DGY-09-192, a bivalent degrader that couples the pan-FGFR inhibitor BGJ398 to a CRL2VHL E3 ligase recruiting ligand, which preferentially induces FGFR1&2 degradation while largely sparing FGFR3&4. DGY-09-192 exhibited two-digit nanomolar DC50s for both wildtype FGFR2 and several FGFR2-fusions, resulting in degradation-dependent antiproliferative activity in representative gastric cancer and cholangiocarcinoma cells. Importantly, DGY-09-192 induced degradation of a clinically relevant FGFR2 fusion protein in a xenograft model. Taken together, we demonstrate that DGY-09-192 has potential as a prototype FGFR degrader.
https://ift.tt/2ReugeG
https://doi.org/10.1210/endocr/bqaa244
https://pubmed.ncbi.nlm.nih.gov/33508115
Abstract
Obesity and related metabolic disorders have become epidemic diseases. Intermittent fasting has been shown to promote adipose tissue angiogenesis and have an anti-obesity feature, however, the mechanisms of how intermittent fasting modulates adipose tissues angiogenesis are poorly understood. We investigated the effect of fasting on vascular endothelial growth factor (VEGF) levels in white adipose tissues (WAT) and the function of fibroblast growth factor 21 (FGF21) in 1-time fasting and long-term intermittent fasting-induced VEGF expression. In the current study, fasting induced a selective and drastic elevation of VEGF levels in WAT, which did not occur in interscapular brown adipose tissue and liver. The fasting-induced Vegfa expression occurred predominantly in mature adipocytes, but not in the stromal vascular fraction in epididymal WAT and inguinal WAT (iWAT). Furthermore, a single bolus of recombinant mouse FGF21 injection increased VEGF levels in WAT. Long-term intermittent fasting for 16 weeks increased WAT angiogenesis, iWAT browning, and improved insulin resistance and inflammation, but the effect was blunted in FGF21 liver-specific knockout mice. In summary, these data suggest that FGF21 is a potent regulator of VEGF levels in WAT. The interorgan FGF21 signaling-induced WAT angiogenesis by VEGF could be a potential new therapeutic target in combination with obesity-related metabolic disorders.
------------------------------------------ Info ------------------------------------------
Open Access: True
Authors: Lun Hua - Jing Li - Bin Feng - Dandan Jiang - Xuemei Jiang - Ting Luo - Lianqiang Che - Shengyu Xu - Yan Lin - Zhengfeng Fang - De Wu - Yong Zhuo -
Additional links:
https://europepmc.org/articles/PMC6483847/figure/F4/
https://europepmc.org/articles/PMC6483847/
The pathophysiological significance of increased serum FGF21 concentrations in ESRD remains undefined. It is also not known whether the very high levels of FGF21 in ESRD patients represent an adaptation or maladaptation, i.e. whether it is protective or deleterious to the patient.
Abstract: Aberrant activation of FGFR signaling occurs in many cancers, and ATPβcompetitive FGFR inhibitors have received regulatory approval. Despite demonstrating clinical efficacy, these inhibitors exhibit doseβlimiting toxicity, potentially due to a lack of selectivity amongst the FGFR family and are poorly tolerated. Here, we report the discovery and characterization of DGYβ09β192, a bivalent degrader that couples the panβFGFR inhibitor BGJ398 to a CRL2 VHL E3 ligase recruiting ligand, which preferentially induces FGFR1&2 degradation while largely sparing FGFR3&4. DGYβ09β192 exhibited two βdigit nanomolar DC 50 s for both wildtype FGFR2 and several FGFR2βfusions, resulting in degradationβdependent antiproliferative activity in representative gastric cancer and cholangiocarcinoma cells. Importantly, DGYβ09β192 induced degradation of a clinically relevant FGFR2 fusion protein in a xenograft model. Taken together, we demonstrate that DGYβ09β192 has potential as a prototype FGFR degrader.
https://ift.tt/2ReugeG
