LP 533401

• CAT Number: R043824
• CAS Number: 945976-43-2
• Molecular Formula: C27H22F4N4O3
• Molecular Weight: 526.492
• Purity: ≥95%
• Target: tryptophan hydroxylase 1 inhibitor
• Storage: -20°C
• IUPAC Name: (2S)-2-amino-3-[4-[2-amino-6-[2,2,2-trifluoro-1-[4-(3-fluorophenyl)phenyl]ethoxy]pyrimidin-4-yl]phenyl]propanoic acid
• InChI: InChI=1S/C27H22F4N4O3/c28-20-3-1-2-19(13-20)16-8-10-18(11-9-16)24(27(29,30)31)38-23-14-22(34-26(33)35-23)17-6-4-15(5-7-17)12-21(32)25(36)37/h1-11,13-14,21,24H,12,32H2,(H,36,37)(H2,33,34,35)/t21-,24?/m0/s1
• InChIKey: JZWUKILTKYJLCN-XEGCMXMBSA-N
• SMILES: C1=CC(=CC(=C1)F)C2=CC=C(C=C2)C(C(F)(F)F)OC3=NC(=NC(=C3)C4=CC=C(C=C4)CC(C(=O)O)N)N

LP533401 is an inhibitor of tryptophan hydroxylase 1, which regulates serotonin production in the gut. LP533401 has an anabolic effect in bone. Inhibiting GDS biosynthesis could become a new anabolic treatment for osteoporosis.

Reference

1: Lima GM, Corazza BJ, Moraes RM, de Oliveira FE, de Oliveira LD, Franco GC, Perrien DS, Elefteriou F, Anbinder AL. The effect of an inhibitor of gut serotonin (LP533401) during the induction of periodontal disease. J Periodontal Res. 2016 Oct;51(5):661-8. doi: 10.1111/jre.12346. PubMed PMID: 26740292.2: Zong JC, Wang X, Zhou X, Wang C, Chen L, Yin LJ, He BC, Deng ZL. Gut-derived serotonin induced by depression promotes breast cancer bone metastasis through the RUNX2/PTHrP/RANKL pathway in mice. Oncol Rep. 2016 Feb;35(2):739-48. doi: 10.3892/or.2015.4430. PubMed PMID: 26573960.3: Krevvata M, Silva BC, Manavalan JS, Galan-Diez M, Kode A, Matthews BG, Park D, Zhang CA, Galili N, Nickolas TL, Dempster DW, Dougall W, Teruya-Feldstein J, Economides AN, Kalajzic I, Raza A, Berman E, Mukherjee S, Bhagat G, Kousteni S. Inhibition of leukemia cell engraftment and disease progression in mice by osteoblasts. Blood. 2014 Oct 30;124(18):2834-46. doi: 10.1182/blood-2013-07-517219. PubMed PMID: 25139351; PubMed Central PMCID: PMC4314530.4: Abid S, Houssaini A, Chevarin C, Marcos E, Tissot CM, Gary-Bobo G, Wan F, Mouraret N, Amsellem V, Dubois-Randé JL, Hamon M, Adnot S. Inhibition of gut- and lung-derived serotonin attenuates pulmonary hypertension in mice. Am J Physiol Lung Cell Mol Physiol. 2012 Sep 15;303(6):L500-8. doi: 10.1152/ajplung.00049.2012. PubMed PMID: 22797248.5: Inose H, Zhou B, Yadav VK, Guo XE, Karsenty G, Ducy P. Efficacy of serotonin inhibition in mouse models of bone loss. J Bone Miner Res. 2011 Sep;26(9):2002-11. doi: 10.1002/jbmr.439. PubMed PMID: 21608033.6: Karsenty G, Yadav VK. Regulation of bone mass by serotonin: molecular biology and therapeutic implications. Annu Rev Med. 2011;62:323-31. doi: 10.1146/annurev-med-090710-133426. Review. PubMed PMID: 21073335.7: Yadav VK, Balaji S, Suresh PS, Liu XS, Lu X, Li Z, Guo XE, Mann JJ, Balapure AK, Gershon MD, Medhamurthy R, Vidal M, Karsenty G, Ducy P. Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat Med. 2010 Mar;16(3):308-12. doi: 10.1038/nm.2098. PubMed PMID: 20139991; PubMed Central PMCID: PMC2836724.