THX-B

THX-B is a potent and non-peptidic p75NTR (neurotrophin receptor p75) antagonist. THX-B can be used in the research of diabetic kidney disease, neurodegenerative and inflammatory disorders[1][2][3].

Signaling Pathways >> GPCR/G Protein >> Neurotensin Receptor

Research Areas >> Metabolic Disease

Research Areas >> Neurological Disease

THX-B (10 μM, 4 days) decreases proliferation of myoblasts[1]. THX-B (10 μM, 1 h) inhibits NGF-induced phosphorylation of ERK1/2 in C2C12 myoblasts[1]. THX-B (20 μM, 24 h) decreases photoreceptor cell death and reactive gliosis in cultured rd10 retinas[2]. Western Blot Analysis[1] Cell Line: C2C12 myoblasts Concentration: 10 μM Incubation Time: Pre-treated for 1 hour Result: Inhibited βNGF-induced ERK2 phosphorylation by 67%. Inhibited proNGF-induced ERK2 phosphorylation by 90%. Immunofluorescence[1] Cell Line: Cultured P22 rd10 retinas. Concentration: 20 μM Incubation Time: 24 h Result: Attenuated the thickening and enlargement of processes of astrocytes and Müller glia cells.

THX-B (50 μg in 125 μL PBS, i.p. weekly for 4 weeks) improves bladder function in a mouse model of diabetic voiding dysfunction[3]. THX-B (2 μL of 2 μg/μL, IVT injection, a single dose) elicits a neuroprotective effect on photoreceptor cells in P17 rd10 mice[2]. THX-B (40 μg in 20 μL, IVT injection) resolves the inflammatory, vascular, and neurodegenerative phases of the retinal pathology[4]. Animal Model: Mouse model of diabetic voiding dysfunction Dosage: 50 μg in 125 μL PBS Administration: Intraperitoneal injection (i.p.) Result: Prevented bladder weight increase, which was 18% (95% CI 3%, 32%) and 37% (95% CI 14%, 60%) lower after 2 and 4 weeks of treatment. Animal Model: P17 rd10 mice[1] Dosage: 2 μL of 2 μg/μL, single dose Administration: Intravitreal (IVT) injected in one eye Result: Increased the number of photoreceptor rows as well as the ONL/INL ratio. Decreased the total number of microglial cells in the treated retinas, as well as some of the inflammatory signs, such as GFAP, α2M and the proinflammatory cytokines IL-1β and TNFα.

[1]. Keren Ettinger, et al. Nerve growth factor stimulation of ERK1/2 phosphorylation requires both p75^NTR and α9β1 integrin and confers myoprotection towards ischemia in C2C12 skeletal muscle cell model. Cell Signal. 2012 Dec;24(12):2378-88.

[2]. María Platón-Corchado, et al. p75^NTR antagonists attenuate photoreceptor cell loss in murine models of retinitis pigmentosa. Cell Death Dis. 2017 Jul 13;8(7):e2922.

[3]. Abubakr H Mossa, et al. Antagonism of proNGF or its receptor p75 NTR reverses remodelling and improves bladder function in a mouse model of diabetic voiding dysfunction. Diabetologia. 2020 Sep;63(9):1932-1946.

[4]. Alba Galan, et al. Subconjunctival Delivery of p75NTR Antagonists Reduces the Inflammatory, Vascular, and Neurodegenerative Pathologies of Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2017 Jun 1;58(7):2852-2862.