SHP099

Last updated

SHP099
SHP099 structure.png
Clinical data
Drug class SHP2 inhibitor
Identifiers
  • 6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazin-2-amine
CAS Number
PubChem CID
ChemSpider
ChEMBL
PDB ligand
Chemical and physical data
Formula C16H19Cl2N5
Molar mass 352.26 g·mol−1
3D model (JSmol)
  • CC1(CCN(CC1)C2=CN=C(C(=N2)N)C3=C(C(=CC=C3)Cl)Cl)N
  • InChI=1S/C16H19Cl2N5/c1-16(20)5-7-23(8-6-16)12-9-21-14(15(19)22-12)10-3-2-4-11(17)13(10)18/h2-4,9H,5-8,20H2,1H3,(H2,19,22)
  • Key:YGUFCDOEKKVKJK-UHFFFAOYSA-N

SHP099 is a drug that acts as an inhibitor of the protein tyrosine phosphatase enzyme SHP-2 (PTPN11). It was developed as a potential agent for the treatment of cancer, but while it is potent, orally active and effective at inhibiting SHP-2 activity and slowing tumor growth, it was not developed for clinical use because of dose-limiting side effects. However it continues to be widely used in cancer research and a number of related derivatives have been developed. [1] [2] [3] [4] [5] [6] [7] It has also been used to research the role of SHP-2 in other processes such as regulation of bone growth during development. [8] [9]

See also

References

  1. ↑ Chen YN, LaMarche MJ, Chan HM, Fekkes P, Garcia-Fortanet J, Acker MG, et al. (July 2016). "Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases". Nature. 535 (7610): 148–152. Bibcode:2016Natur.535..148C. doi:10.1038/nature18621. PMID   27362227.
  2. ↑ Garcia Fortanet J, Chen CH, Chen YN, Chen Z, Deng Z, Firestone B, et al. (September 2016). "Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor". Journal of Medicinal Chemistry. 59 (17): 7773–7782. doi:10.1021/acs.jmedchem.6b00680. OSTI   1404987. PMID   27347692.
  3. ↑ Guo W, Xu Q (November 2020). "Phosphatase-independent functions of SHP2 and its regulation by small molecule compounds". Journal of Pharmacological Sciences. 144 (3): 139–146. doi:10.1016/j.jphs.2020.06.002. PMID   32921395.
  4. ↑ Wu J, Zhang H, Zhao G, Wang R (2021). "Allosteric Inhibitors of SHP2: An Updated Patent Review (2015-2020)". Current Medicinal Chemistry. 28 (19): 3825–3842. doi:10.2174/1568011817666200928114851. PMID   32988341.
  5. ↑ Petrocchi A, Ciammaichella A (May 2024). "A patent review of SHP2 allosteric inhibitors (2018-present)". Expert Opinion on Therapeutic Patents. 34 (5): 383–396. doi:10.1080/13543776.2024.2365410. PMID   38842843.
  6. ↑ Marotta M, Zirpoli S, Prevete N, De Simone C, Di Cristofano A, Liotti F, et al. (September 2025). "SHP2 is a multifunctional target in anaplastic thyroid carcinoma: Cell intrinsic and immune-dependent anti-tumor effects". Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 190 118384. doi:10.1016/j.biopha.2025.118384. PMID   40752423.
  7. ↑ Jama M, Mosa FE, Overduin M, Barakat KH (2026). "Structural insights into the binding modes of SHP2 allosteric inhibitors". In Silico Pharmacology. 14 (1) 51. doi:10.1007/s40203-025-00551-x. PMC  12847482. PMID   41613633.
  8. ↑ Jensen NR, Kelly RR, Kelly KD, Khoo SK, Sidles SJ, LaRue AC (April 2023). "From Stem to Sternum: The Role of Shp2 in the Skeleton". Calcified Tissue International. 112 (4): 403–421. doi:10.1007/s00223-022-01042-3. PMID   36422682.
  9. ↑ Zhang Q, Li N, Dai ZZ, Liu XM, Ding J, Sha L, et al. (2025). "SHP2 inhibition by SHP099 attenuates IL-6-driven osteoclastogenesis in growth plate injury". Frontiers in Immunology. 16 1659230. doi: 10.3389/fimmu.2025.1659230 . PMC   12394037 . PMID   40895539.
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