| Identification | Back Directory | [Name]
LX-5061 | [CAS]
1365060-22-5 | [Synonyms]
LX-5061
LP 922056
2-((6-chloro-7-cyclopropylthieno[3,2-d]pyriMidin-4-yl)thio)acetic acid
Acetic acid, 2-[(6-chloro-7-cyclopropylthieno[3,2-d]pyrimidin-4-yl)thio]-
cortical,Pectinacetylesterase,thickness,orally,femur,inhibit,Wnt,lipase,bone,LP-922056,Notum,LP 922056,Inhibitor,LP922056,midshaft | [Molecular Formula]
C11H9ClN2O2S2 | [MDL Number]
MFCD22572369 | [MOL File]
1365060-22-5.mol | [Molecular Weight]
300.78 |
| Chemical Properties | Back Directory | [storage temp. ]
Store at -20°C | [solubility ]
Soluble in DMSO | [form ]
Solid | [color ]
White to light yellow | [InChI]
1S/C11H9ClN2O2S2/c12-10-7(5-1-2-5)8-9(18-10)11(14-4-13-8)17-3-6(15)16/h4-5H,1-3H2,(H,15,16) | [InChIKey]
LJYRIWUQISYYHA-UHFFFAOYSA-N | [SMILES]
[s]1c2c(ncnc2SCC(=O)O)c(c1Cl)C3CC3 |
| Hazard Information | Back Directory | [Uses]
LP-922056 is an orally active, highly potent Notum Pectinacetylesterase inhibitor with EC50s of 21 nM, 55 nM in human and mouse cellular assay, respectively. LP-922056 significantly increases midshaft femur cortical bone thickness in mice and rats[1][2]. | [Biological Activity]
LP-922056 is an orally activepotent and selective NOTUM pectinacetylesterase inhibitor th at activates Wnt signaling. LP-922056 stimulates endocortical bone formation in rodents and in humanized NOTUM mouse line. | [in vivo]
LP-922056 (compound 44; 3-30 mg/kg; oral gavage; daily; for 25 days) causes an increase in cortical bone thickness at all doses[1].
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LP-922056 (10 mg/kg; orally) achieves high Cmax (129 μM) and AUC (1533 μM?h)[1].
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LP-922056 (10?mg/kg; daily diet; for 4 weeks) increases cortical bone thickness and strength in midshaft femur, bone mass in the femoral neck and vertebral body cortical shell in Twelve-week-old male mice[2].
| Animal Model: | F1 male hybrid (129xC57) mice at 8.7 weeks of age[1] | | Dosage: | 3, 10, 30 mg/kg | | Administration: | Oral gavage; daily; for 25 days | | Result: | Caused an increase in cortical bone thickness at all doses.
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| Animal Model: | Mouse[1] | | Dosage: | 10 mg/kg (Pharmacokinetic Analysis) | | Administration: | Orally | | Result: | Achieved high Cmax (129 μM) and AUC (1533 μM?h) while has low clearance (0.49 mL/min?kg) and volume of distribution (0.13 L/kg).
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| [storage]
Store at -20°C | [References]
[1] James E Tarver Jr, et al. Stimulation of cortical bone formation with thienopyrimidine based inhibitors of Notum Pectinacetylesterase. Bioorg Med Chem Lett. 2016 Mar 15;26(6):1525-1528. DOI:10.1016/j.bmcl.2016.02.021
[2] Robert Brommage, et al. NOTUM inhibition increases endocortical bone formation and bone strength. Bone Res. 2019 Jan 8;7:2. DOI:10.1038/s41413-018-0038-3 |
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