Tropomyosin receptor kinase B (TrkB), also known as tyrosine receptor kinase B, or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the NTRK2 gene. TrkB is a receptor for brain-derived neurotrophic factor (BDNF).
Flavones, are a class of flavonoids based on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one).
In enzymology, an apigenin 4'-O-methyltransferase is an enzyme that catalyzes the chemical reaction
In enzymology, a flavone apiosyltransferase is an enzyme that catalyzes the chemical reaction
The chemical formula C15H10O4 (molar mass : 254.242 g/mol, exact mass : 254.057909) may refer to:
Diosmetin, also known as 5,7,3'-trihydroxy-4'-methoxyflavone, is an O-methylated flavone, a chemical compound that can be found in the Caucasian vetch.
2,4,6-Trihydroxyacetophenone (THAP) is a chemical compound that is a deritavite of phloroglucinol.
Acacetin is an O-methylated flavone found in Robinia pseudoacacia, Turnera diffusa (damiana), Betula pendula, and in the fern Asplenium normale.
Pratol is a flavonoid, 4′-O-methylated 4′,7-dihydroxyflavone. It can be found in Trifolium pratense.
Norwogonin, also known as 5,7,8-trihydroxyflavone (5,7,8-THF), is a flavone, a naturally occurring flavonoid-like chemical compound which is found in Scutellaria baicalensis. It has been found to act as an agonist of the TrkB, the main signaling receptor of brain-derived neurotrophic factor (BDNF), and appears to possess roughly the same activity in this regard to that of the closely related but more well-known 7,8-dihydroxyflavone (7,8-DHF).
Deoxygedunin, or 14,15-deoxygedunin, is a naturally occurring tetranortriterpenoid isolated from the Indian neem tree, a plant that has been used in India since ancient times as a remedy for various ailments. Deoxygedunin has been found to act as a potent, selective, small-molecule agonist of TrkB, the main receptor of brain-derived neurotrophic factor (BDNF). It produces TrkB-dependent neurotrophic and neuroprotective effects in mice and enhances learning processes. In addition, deoxygedunin evokes rapid TrkB-dependent antidepressant-like effects in the forced swim test, an animal model of depression, similarly to 7,8-dihydroxyflavone (7,8-DHF) and ketamine, and notably with a greater potency than 7,8-DHF. The compound was discovered by the same group that identified 7,8-DHF and N-acetylserotonin as TrkB agonists.
ANA-12 is a selective, small-molecule non-competitive antagonist of TrkB, the main receptor of brain-derived neurotrophic factor (BDNF). The compound crosses the blood-brain-barrier and exerts central TrkB blockade, producing effects as early as 30 minutes and as long as 6 hours following intraperitoneal injection in mice. It blocks the neurotrophic actions of BDNF without compromising neuron survival.
R7 is a small-molecule flavonoid and orally active, potent, and selective agonist of the tropomyosin receptor kinase B (TrkB) – the main signaling receptor for the neurotrophin brain-derived neurotrophic factor (BDNF) – which is under development for the treatment of Alzheimer's disease. It is a structural modification and prodrug of 7,8-dihydroxyflavone (7,8-DHF) with improved potency and pharmacokinetics, namely oral bioavailability and duration. R7 was synthesized by the same researchers who were involved in the discovery of 7,8-DHF. A patent was filed for R7 in 2013 and was published in 2015. In 2016, it was reported to be in the preclinical stage of development. R7 was superseded by R13 because while R7 had a good drug profile in animals, it showed almost no conversion into 7,8-DHF in human liver microsomes.
7,8,3′-Trihydroxyflavone (7,8,3'-THF) is a flavone and small-molecule agonist of TrkB, the main receptor of brain-derived neurotrophic factor (BDNF), that was derived from 7,8-dihydroxyflavone (7,8-DHF). Relative to 7,8-DHF, 7,8,3'-THF is 2–3-fold more potent in vitro as a TrkB agonist. 7,3’-Dihydroxyflavone (7,3'-DHF) is also more potent than 7,8-DHF in vitro, indicating that a 3'-hydroxy group on the B-ring enhances TrkB agonistic activity. 7,8,3'-THF has been tested in vivo and was found to produce TrkB-dependent neuroprotective effects in mice similarly to 7,8-DHF.
4'-Dimethylamino-7,8-dihydroxyflavone (4'-DMA-7,8-DHF) is a synthetic flavone and selective small-molecule agonist of TrkB, the main receptor of brain-derived neurotrophic factor (BDNF), which was derived from structural modification of 7,8-dihydroxyflavone (7,8-DHF). Relative to 7,8-DHF, 4'-DMA-7,8-DHF possesses higher agonistic activity at TrkB, is significantly more potent than 7,8-DHF both in vitro and in vivo, and has a longer duration of action. The compound has been found to produce neuroprotective, neurogenic, and antidepressant-like effects in animals.
R13 is a small-molecule flavonoid and orally active, potent, and selective agonist of the tropomyosin receptor kinase B (TrkB) – the main signaling receptor for the neurotrophin brain-derived neurotrophic factor (BDNF) – which is under development for the potential treatment of Alzheimer's disease. It is a structural modification and prodrug of 7,8-dihydroxyflavone (7,8-DHF) with improved potency and pharmacokinetics, namely oral bioavailability and duration. The compound is a replacement for the earlier 7,8-DHF prodrug R7 and has similar properties to it. It was developed because while R7 displayed a good drug profile in animal studies, it showed almost no conversion into 7,8-DHF in human liver microsomes. In contrast to R7, R13 is readily hydrolyzed into 7,8-DHF in human liver microsomes.
