LMT-28

LMT-28
Identifiers
	IUPAC name (4S)-3-[(2S,3S)-3-hydroxy-2-methyl-4-methylidenenonanoyl]-4-propan-2-yl-1,3-oxazolidin-2-one;
CAS Number	1239600-18-0;
PubChem CID	49846977;
ChemSpider	58824361;
ChEMBL	ChEMBL3765505;
Chemical and physical data
Formula	C17H29NO4
Molar mass	311.422 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCCCCC(=C)[C@H]([C@H](C)C(=O)N1[C@H](COC1=O)C(C)C)O;
	InChI InChI=1S/C17H29NO4/c1-6-7-8-9-12(4)15(19)13(5)16(20)18-14(11(2)3)10-22-17(18)21/h11,13-15,19H,4,6-10H2,1-3,5H3/t13-,14+,15+/m0/s1; Key:UDXWSYOXIRPYFK-RRFJBIMHSA-N;

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]

References

↑ Hong SS, Choi JH, Lee SY, Park YH, Park KY, Lee JY, et al. (July 2015). "A Novel Small-Molecule Inhibitor Targeting the IL-6 Receptor β Subunit, Glycoprotein 130". Journal of Immunology. 195 (1): 237–245. doi:10.4049/jimmunol.1402908. PMID 26026064.
↑ Pérez S, Rius-Pérez S, Finamor I, Martí-Andrés P, Prieto I, García R, et al. (January 2019). "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. doi:10.1002/path.5166. hdl:10261/177634. PMID 30221360.
↑ Park YH, Kim HJ, Lee K, Choi Y, Heo TH (February 2020). "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. Bibcode:2020BBRC..522.1030P. doi:10.1016/j.bbrc.2019.11.183. PMID 31818460.
↑ Ahn SH, Heo TH, Jun HS, Choi Y (April 2020). "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. doi:10.5713/ajas.19.0463. PMC 7054612. PMID 31480155.
↑ Matsukawa S, Kai S, Seo H, Suzuki K, Fukuda K (2021). "Activation of the β-adrenergic receptor exacerbates lipopolysaccharide-induced wasting of skeletal muscle cells by increasing interleukin-6 production". PLOS ONE. 16 (5) e0251921. Bibcode:2021PLoSO..1651921M. doi:10.1371/journal.pone.0251921. PMC 8130926. PMID 34003837.
↑ Bao J, Zhang P, Wu B, Wang J, Li S, Li A, et al. (April 2023). "Gp130 Promotes Inflammation via the STAT3/JAK2 Pathway in Allergic Conjunctivitis". Investigative Ophthalmology & Visual Science. 64 (4): 5. doi:10.1167/iovs.64.4.5. PMC 10082384. PMID 37022703.
↑ Liu QQ, Wu WW, Yang J, Wang RB, Yuan LL, Peng PZ, et al. (2023). "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 9330439. doi:10.1155/2023/9330439. PMC 9839413. PMID 36643585.
↑ Tran QH, Nguyen QT, Tran TN, Tran TD, Le MT, Trinh DT, et al. (October 2023). "Identification of small molecules as potential inhibitors of interleukin 6: a multi-computational investigation". Molecular Diversity. 27 (5): 2315–2330. doi:10.1007/s11030-022-10558-7. PMC 9628397. PMID 36319930.
↑ Krishna Swaroop A, Krishnan Namboori PK, Esakkimuthukumar M, Praveen TK, Nagarjuna P, Patnaik SK, et al. (September 2023). "Leveraging decagonal in-silico strategies for uncovering IL-6 inhibitors with precision". Computers in Biology and Medicine. 163 107231. doi:10.1016/j.compbiomed.2023.107231. PMID 37421735.
↑ Zia K, Nur-E-Alam M, Ahmad A, Ul-Haq Z (December 2024). "Taming the cytokine storm: small molecule inhibitors targeting IL-6/IL-6α receptor". Molecular Diversity. 28 (6): 4151–4165. doi:10.1007/s11030-023-10805-5. PMID 38366102.

[1] Hong SS, Choi JH, Lee SY, Park YH, Park KY, Lee JY, et al. (July 2015). "A Novel Small-Molecule Inhibitor Targeting the IL-6 Receptor β Subunit, Glycoprotein 130". Journal of Immunology. 195 (1): 237–245. doi:10.4049/jimmunol.1402908. PMID 26026064.

[2] Pérez S, Rius-Pérez S, Finamor I, Martí-Andrés P, Prieto I, García R, et al. (January 2019). "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. doi:10.1002/path.5166. hdl:10261/177634. PMID 30221360.

[3] Park YH, Kim HJ, Lee K, Choi Y, Heo TH (February 2020). "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. Bibcode:2020BBRC..522.1030P. doi:10.1016/j.bbrc.2019.11.183. PMID 31818460.

[4] Ahn SH, Heo TH, Jun HS, Choi Y (April 2020). "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. doi:10.5713/ajas.19.0463. PMC 7054612. PMID 31480155.

[5] Matsukawa S, Kai S, Seo H, Suzuki K, Fukuda K (2021). "Activation of the β-adrenergic receptor exacerbates lipopolysaccharide-induced wasting of skeletal muscle cells by increasing interleukin-6 production". PLOS ONE. 16 (5) e0251921. Bibcode:2021PLoSO..1651921M. doi:10.1371/journal.pone.0251921. PMC 8130926. PMID 34003837.

[6] Bao J, Zhang P, Wu B, Wang J, Li S, Li A, et al. (April 2023). "Gp130 Promotes Inflammation via the STAT3/JAK2 Pathway in Allergic Conjunctivitis". Investigative Ophthalmology & Visual Science. 64 (4): 5. doi:10.1167/iovs.64.4.5. PMC 10082384. PMID 37022703.

[7] Liu QQ, Wu WW, Yang J, Wang RB, Yuan LL, Peng PZ, et al. (2023). "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 9330439. doi:10.1155/2023/9330439. PMC 9839413. PMID 36643585.

[8] Tran QH, Nguyen QT, Tran TN, Tran TD, Le MT, Trinh DT, et al. (October 2023). "Identification of small molecules as potential inhibitors of interleukin 6: a multi-computational investigation". Molecular Diversity. 27 (5): 2315–2330. doi:10.1007/s11030-022-10558-7. PMC 9628397. PMID 36319930.

[9] Krishna Swaroop A, Krishnan Namboori PK, Esakkimuthukumar M, Praveen TK, Nagarjuna P, Patnaik SK, et al. (September 2023). "Leveraging decagonal in-silico strategies for uncovering IL-6 inhibitors with precision". Computers in Biology and Medicine. 163 107231. doi:10.1016/j.compbiomed.2023.107231. PMID 37421735.

[10] Zia K, Nur-E-Alam M, Ahmad A, Ul-Haq Z (December 2024). "Taming the cytokine storm: small molecule inhibitors targeting IL-6/IL-6α receptor". Molecular Diversity. 28 (6): 4151–4165. doi:10.1007/s11030-023-10805-5. PMID 38366102.

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This page was redesigned at the edge.

LMT-28

See also

References