SHP099

SHP099
Clinical data
Drug class	SHP2 inhibitor
Identifiers
	IUPAC name 6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazin-2-amine;
CAS Number	1801747-42-1;
PubChem CID	118238298;
ChemSpider	58171740;
ChEMBL	ChEMBL4060033;
PDB ligand	5OD (PDBe, RCSB PDB);
Chemical and physical data
Formula	C16H19Cl2N5
Molar mass	352.26 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1(CCN(CC1)C2=CN=C(C(=N2)N)C3=C(C(=CC=C3)Cl)Cl)N;
	InChI 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]

References

↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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. 190 118384. doi:10.1016/j.biopha.2025.118384. PMID 40752423.
↑ 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.
↑ 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.
↑ 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.

[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. 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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SHP099

See also

References