YKL-05-099

Last updated

YKL-05-099
YKL-05-099 structure.png
Identifiers
  • 3-(2-chloro-6-methylphenyl)-7-[2-methoxy-4-(1-methylpiperidin-4-yl)anilino]-1-(5-methoxypyridin-2-yl)-4H-pyrimido[4,5-d]pyrimidin-2-one
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
Formula C32H34ClN7O3
Molar mass 600.12 g·mol−1
3D model (JSmol)
  • CC1=C(C(=CC=C1)Cl)N2CC3=CN=C(N=C3N(C2=O)C4=NC=C(C=C4)OC)NC5=C(C=C(C=C5)C6CCN(CC6)C)OC
  • InChI=1S/C32H34ClN7O3/c1-20-6-5-7-25(33)29(20)39-19-23-17-35-31(37-30(23)40(32(39)41)28-11-9-24(42-3)18-34-28)36-26-10-8-22(16-27(26)43-4)21-12-14-38(2)15-13-21/h5-11,16-18,21H,12-15,19H2,1-4H3,(H,35,36,37)
  • Key:VQINULODWGEVBB-UHFFFAOYSA-N

YKL-05-099 is an experimental drug which acts as an inhibitor of the salt-inducible kinase (SIK) enzymes. It has antiinflammatory effects and is used for research into the potential applications of salt-inducible kinase inhibitors in treating several conditions including leukemia, osteoporosis and obesity. [1] [2] [3] [4] [5] [6] [7]

References

  1. ↑ Sundberg TB, Liang Y, Wu H, Choi HG, Kim ND, Sim T, et al. (August 2016). "Development of Chemical Probes for Investigation of Salt-Inducible Kinase Function in Vivo". ACS Chemical Biology. 11 (8): 2105–2111. doi:10.1021/acschembio.6b00217. PMC   4992440 . PMID   27224444.
  2. ↑ Wein MN, Liang Y, Goransson O, Sundberg TB, Wang J, Williams EA, et al. (October 2016). "SIKs control osteocyte responses to parathyroid hormone". Nature Communications. 7: 13176. Bibcode:2016NatCo...713176W. doi:10.1038/ncomms13176. PMC   5075806 . PMID   27759007.
  3. ↑ Tarumoto Y, Lin S, Wang J, Milazzo JP, Xu Y, Lu B, et al. (January 2020). "Salt-inducible kinase inhibition suppresses acute myeloid leukemia progression in vivo". Blood. 135 (1): 56–70. doi:10.1182/blood.2019001576. PMC   6940199 . PMID   31697837.
  4. ↑ Tang CC, Castro Andrade CD, O'Meara MJ, Yoon SH, Sato T, Brooks DJ, et al. (June 2021). "Dual targeting of salt inducible kinases and CSF1R uncouples bone formation and bone resorption". eLife. 10. doi: 10.7554/eLife.67772 . PMC   8238509 . PMID   34160349.
  5. ↑ Canté-Barrett K, Meijer MT, Cordo' V, Hagelaar R, Yang W, Yu J, Smits WK, Nulle ME, Jansen JP, Pieters R, Yang JJ, Haigh JJ, Goossens S, Meijerink JP. MEF2C opposes Notch in lymphoid lineage decision and drives leukemia in the thymus. JCI Insight. 2022 Jul 8;7(13):e150363. doi : 10.1172/jci.insight.150363 PMID   35536646
  6. ↑ Shi F, de Fatima Silva F, Liu D, Patel HU, Xu J, Zhang W, et al. (August 2023). "Salt-inducible kinase inhibition promotes the adipocyte thermogenic program and adipose tissue browning". Molecular Metabolism. 74: 101753. doi:10.1016/j.molmet.2023.101753. PMC   10319839 . PMID   37321371.
  7. ↑ Momenzadeh K, Yeritsyan D, Abbasian M, Kheir N, Hanna P, Wang J, et al. (2024). "Stimulation of fracture mineralization by salt-inducible kinase inhibitors". Frontiers in Bioengineering and Biotechnology. 12: 1450611. doi: 10.3389/fbioe.2024.1450611 . PMC   11445660 . PMID   39359266.
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