Chemistry:LMT-28
LMT-28 is an experimental drug which was the first molecule discovered that acts as an antagonist of IL6R, the receptor for Interleukin-6, and so blocks its activity in the body. Interleukin-6 is a cytokine signalling molecule which plays a key role in inflammation, so blocking IL6R is useful for alleviating a number of disease processes in which inflammation plays a part. Previously it has only been possible to block cytokine activity using biologics such as targeted antibodies which have various disadvantages, so the development of small molecule inhibitors is a considerable advance. LMT-28 is of relatively low potency and is unlikely to be developed as a medicine, but is useful for pharmaceutical research into the processes mediated by IL6R,[1][2][3][4][5][6][7] and as a successful proof of concept it makes it likely that more potent small molecule antagonists for IL6R and other interleukin receptors will be developed in future.[8][9][10]
See also
- IL-4-inhibitor-1
- Sarilumab
- Tocilizumab
References
- ↑ "A Novel Small-Molecule Inhibitor Targeting the IL-6 Receptor β Subunit, Glycoprotein 130". Journal of Immunology 195 (1): 237–245. July 2015. doi:10.4049/jimmunol.1402908. PMID 26026064.
- ↑ "Obesity causes PGC-1α deficiency in the pancreas leading to marked IL-6 upregulation via NF-κB in acute pancreatitis". The Journal of Pathology 247 (1): 48–59. January 2019. doi:10.1002/path.5166. PMID 30221360.
- ↑ "Combination of gp130-targeting and TNF-targeting small molecules in alleviating arthritis through the down-regulation of Th17 differentiation and osteoclastogenesis". Biochemical and Biophysical Research Communications 522 (4): 1030–1036. February 2020. doi:10.1016/j.bbrc.2019.11.183. PMID 31818460. Bibcode: 2020BBRC..522.1030P.
- ↑ "In vitro and in vivo pharmacokinetic characterization of LMT-28 as a novel small molecular interleukin-6 inhibitor". Asian-Australasian Journal of Animal Sciences 33 (4): 670–677. April 2020. doi:10.5713/ajas.19.0463. PMID 31480155.
- ↑ "Activation of the β-adrenergic receptor exacerbates lipopolysaccharide-induced wasting of skeletal muscle cells by increasing interleukin-6 production". PLOS ONE 16 (5). 2021. doi:10.1371/journal.pone.0251921. PMID 34003837. Bibcode: 2021PLoSO..1651921M.
- ↑ "Gp130 Promotes Inflammation via the STAT3/JAK2 Pathway in Allergic Conjunctivitis". Investigative Ophthalmology & Visual Science 64 (4): 5. April 2023. doi:10.1167/iovs.64.4.5. PMID 37022703.
- ↑ "A GP130-Targeting Small Molecule, LMT-28, Reduces LPS-Induced Bone Resorption around Implants in Diabetic Models by Inhibiting IL-6/GP130/JAK2/STAT3 Signaling". Mediators of Inflammation 2023. 2023. doi:10.1155/2023/9330439. PMID 36643585.
- ↑ "Identification of small molecules as potential inhibitors of interleukin 6: a multi-computational investigation". Molecular Diversity 27 (5): 2315–2330. October 2023. doi:10.1007/s11030-022-10558-7. PMID 36319930.
- ↑ "Leveraging decagonal in-silico strategies for uncovering IL-6 inhibitors with precision". Computers in Biology and Medicine 163. September 2023. doi:10.1016/j.compbiomed.2023.107231. PMID 37421735.
- ↑ "Taming the cytokine storm: small molecule inhibitors targeting IL-6/IL-6α receptor". Molecular Diversity 28 (6): 4151–4165. December 2024. doi:10.1007/s11030-023-10805-5. PMID 38366102.
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