SHP2 Inhibitor

Ellagic acid is a natural antioxidant, and acts as a potent and ATP-competitive inhibitor of CK2 and SHP2, with an IC₅₀ of 40 nM and a K_i of 20 nM.

SHP099 is an allosteric SHP2 inhibitor, with IC₅₀s of 0.690, 1.241, 0.416, 1.968, 2.896 μM for SHP2, SHP2^D61Y, SHP2E69K, SHP2^A72V, SHP2^E76K. SHP099 inhibits cancer cell growth, such as MV4-11 and TF-1 cell (IC₅₀: 0.32 and 1.73 μM). SHP099 inhibits RAS-ERK signaling and inhibits tumor growth.

Batoprotafib (TNO155) is a potent selective and orally active allosteric inhibitor of wild-type SHP2 (IC₅₀=0.011 µM). Batoprotafib has the potential for the study of RTK-dependent malignancies, especially advanced solid tumors.

RMC-4550 is a potent, selective and allosteric inhibitor of SHP2, with an IC₅₀ of 0.583 nM.

Sitneprotafib (JAB-3312) is an orally effective anticancer phosphatase SHP2 inhibitor (IC₅₀: 1.9 nM) with anti-cancer activity. Sitneprotafib has good tolerability and significantly induced tumor regression in a KYSE-520 mouse xenograft model.

NSC-13030 is a SHP2 inhibitor with an IC₅₀ value of 3.2 μM. NSC-13030 reduces the proliferation and viability of breast cancer cells. NSC-13030 is applicable to breast cancer-related research.

BCR-ABL degrader 1 is a hydrophobic tag degrader with GNF‑2 (HY-11007) as the ligand and Boc₂His (HY-185595) as the hydrophobic tag. BCR-ABL degrader 1 mediates the degradation of BCR‑ABL with a DC₅₀ of 19.9 μM. BCR-ABL degrader 1 induces the degradation of BCR-ABL fusion protein via the ubiquitin-proteasome pathway, a process involving Hsp70 and Hsp90. BCR-ABL degrader 1 downregulates p‑STAT5 and p‑SHP2, the downstream signaling molecules of BCR‑ABL. BCR-ABL degrader 1 can be used in the research of chronic myeloid leukemia.

I-0436650 is an orally active SHP2 inhibitor with an IC₅₀ of 4 nM and a K_d value of 0.3 nM. I-0436650 binds allosterically to the channel between the C-SH2, N-SH2 and PTP catalytic domains, locking the protein in an inactive closed conformation. I-0436650 potently inhibits ERK phosphorylation and suppresses MAPK pathway activity. I-0436650 exhibits antiproliferative activity in EGFR- and RAS-dependent cells. I-0436650 can be used in the research of RAS-driven cancers, EGFR-mutated cancers and RTK-driven cancers.

NSC-87877 is a potent inhibitor of Shp2 and Shp1 protein tyrosine phosphatases (SH-PTP2 and SH-PTP1), with IC₅₀ values of 0.318 μM, 0.355 μM shp2 and shp1, respectively. NSC-87877 also inhibits dual-specificity phosphatase 26 (DUSP26).

Vociprotafib (RMC-4630) is an orally active, selective and potent phosphatase SHP2 inhibitor, which blocks activation of the RAS-RAF-MEK-ERK signaling pathway with antitumor activity. Vociprotafib accelerates the time to, and increases the magnitude of, tumor regressions in Osimertinib (HY-15772)-sensitive EGFR-mutant tumors of mice.

SHP099 hydrochloride is a potent, selective and orally available SHP2 inhibitor with an IC₅₀ of 70 nM.

PF-07284892 (ARRY-558) is a potent and orally active SHP2 inhibitor with an IC₅₀ value of 21 nM. PF-07284892 decreases the expression of pERK.

PHPS1 is a potent and selective Shp2 inhibitor with K_is of 0.73, 5.8, 10.7, 5.8, and 0.47 μM for Shp2, Shp2-R362K, Shp1, PTP1B, and PTP1B-Q, respectively.

Migoprotafib (GDC-1971) (compound 199) is a SHP2 inhibitor. Migoprotafib inhibits the MAPK/ERK signaling pathway, and exhibits antitumor activity.

PTP Inhibitor IV is a protein tyrosine phosphatase (PTP) inhibitor that competitively inhibits DUSP14 phosphatase activity with an ₅₀ of 5.21 μM. PTP Inhibitor IV inhibits SHP-2, PTP1B, PTP-ε, PTP Meg-2, PTP-σ, PTP-β, and PTP-μ with ₅₀s of 1.8 μM, 2.5 μM, 8.4 μM, 13 μM, 20 μM, 6.4 μM, and 6.7 μM, respectively.

SPI-112 is a potent, selective and competitive SHP2 (PTPN11) inhibitor with IC₅₀s of 1 μM, 18.3 μM and 14.5 μM for SHP2, protein tyrosine phosphatase (PTP) and PTP1B, respectively.

IACS-13909 is a selective, potent and orally active SHP2 allosteric inhibitor with an IC₅₀ of 15.7 nM and a K_d of 32 nM. IACS-13909 is more selective for SHP2 than other phosphatases (including SHP1). IACS-13909 has antitumor activities and suppresses MAPK pathway signaling in receptor tyrosine kinases (RTK)-dependent cancers.

RMC-0331 (RM-023) is a potent, selective and orally bioavailable SOS1 inhibitor. RMC-0331 is an in vivo tool compound that blocks RAS activation via disruption of the RAS-SOS1 interaction.

JAB-3068 (SHP2-IN-6) is a potent SHP2 inhibitor, extracted from patent WO2017211303A1, compound 7, has an IC₅₀ of 25.8 nM.

Bis(maltolato)oxovanadium(IV) (BMOV) is a potent, reversible, competitive and orally active pan-PTP (protein tyrosine phosphatases) inhibitor. Bis(maltolato)oxovanadium(IV) inhibits HCPTPA, PTP1B, HPTPβ and SHP2 with IC₅₀s of 126 nM, 109 nM, 26 nM and 201 nM, respectively. Bis(maltolato)oxovanadium(IV) is a potent insulin sensitizer.