SHP2 Inhibitor

SHP2-IN-35 (Compound 3f) is the inhibitor for SHP2. SHP2-IN-35 exhibits antiproliferative activity in cancer cells RKO, SW480 and CT26 with IC₅₀ of 5.72 μM, 3.71 μM and 1.42 μM, respectively. SHP2-IN-35 inhibits the PI3K-Akt signaling pathway, regulates the cell cycle associated gene expressions, and induces mitochondrial-related autophagy. SHP2-IN-35 inhibits the expression of certain cytokines and chemokines in the tumor microenvironment (TME), thereby regulating the tumor progression.

SHP2 inhibitor LY6 (LY6) is a selective SHP2 inhibitor with an IC₅₀ of 9.8 μM, showing 7-fold selectivity over SHP1. SHP2 inhibitor LY6 inhibits SHP2-mediated cell signaling pathways and suppresses cell proliferation. SHP2 inhibitor LY6 elicits induces apoptosis and G2/M cell cycle arrest in lung cancer cells. SHP2 inhibitor LY6 can be used for the research of B cell acute lymphoblastic leukemia, acute myeloid leukemia, and lung cancer.

SHP2-IN-5 (compound 1) is an inhibitor of SHP2 (IC₅₀: 97 nM). SHP2 is a non-receptor protein tyrosine phosphatase associated with cell growth and proliferation. SHP2-IN-5 has the potential to inhibit cancer and SHP2-related human diseases.

PF-04577806 is a potent, selective and ATP competitive PKC inhibitor. PF-04577806 shows potent inhibitory activity towards PKCα, PKCβI, PKCβII, PKCγ, and PKCθ with IC₅₀s of 2.4 nM, 8.1 nM, 6.9 nM, 45.9 nM, and 29.5 nM, respectively. PF-04577806 can reverse retinal vascular leakage in diabetic rats.

SHP2 ligand-3 is a PROTAC target protein ligand that can be used to synthesize SHP2 protein degrader-1 (HY-145159).

LXQ-217 is an oral active SHP2 inhibitor with the IC₅₀ of 2.01 μM. LXQ-217 induces apoptosis and inhibits cell growth in vivo and in vitro.

CNBCA is a potent, selective, competitive SHP2 enzyme inhibitor, with the IC₅₀ of 0.87 μM. CNBCA binds to full-length SHP2 and inhibits enzyme activity. CNBCA inhibits pAkt and pERK1/2, and the cell growth of BT474 and MDA-MB468 cells. CNBCA can be used for breast cancer study.

SHP2-IN-44 (Compound 26) is an allosteric and orally active SHP2 inhibitor with an IC₅₀ of 27 ?nM. SHP2-IN-44 also inhibits ERK phosphorylation (IC₅₀ of 299 ?nM) without off-target hERG activity. SHP2-IN-44 has a broad-spectrum anticancer activity, such as juvenile myelomonocytic leukemia, neuroblastoma and breast cancer. SHP2-IN-44 can be used for Noonan syndrome, LEOPARD syndrome and cancers research.

SHP2-IN-26 (Compound 4b) is a highly selective SHP2 allosteric inhibitor with a IC₅₀ value of 3.2 nM. SHP2-IN-26 inhibits the phosphorylation of ERK and AKT in NCI-H358 cells. SHP2-IN-26 has antitumor activity.

PF-03622905 is a potent and ATP-competitive PKC inhibitor with IC₅₀s of 5.6 nM, 14.5 nM, 13 nM, 37.7 nM, and 74.1 nM for PKCα, PKCβI, PKCβII, PKCγ, and PKCθ, respectively. PF-03622905 shows high specificity for PKC over other protein kinases.

SHP2-IN-25 (Compound 6) is a SHP2 allosteric inhibitor, with an IC₅₀ of 225 nM. SHP2-IN-25 can be used for the research of cancer.

LC-SF-14 is a selective dual inhibitor of SHP2 and FGFR (IC₅₀ values are 71.6 and 8.9 nM, respectively). LC-SF-14 inhibits FGFR2-FRS2α-SHP2-MAPK signaling and ERK phosphorylation. LC-SF-14 inhibits the proliferation of KATOIII cancer cells (IC₅₀: 9.2 nM). LC-SF-14 has antitumor activity in the SNU-16 xenograft mouse model. LC-SF-14 can be used in FGFR2-driven gastric cancer research.

TK-684 is a potent and selective allosteric SHP2 inhibitor with IC₅₀ values of 2.1, ＞1000 nM for SHP2^WT, SHP22^PTP, respectively. TK-684 inhibits cell proliferation and induces apoptosis. TK-684 decreases the protein expression of p-AKT, p-ERK.

SHP2-IN-36 (Compound B8) is an allosteric inhibitor of SHP2, with an IC₅₀ value of 9.0 nM. In addition, its IC₅₀ for p-ERK is 40 nM. SHP2-IN-36 also exhibited significant antitumor activity in the KYSE520 xenograft mouse model. SHP2-IN-36 can be used for research in the field of anti-tumor .

SDUY127 is a bivalent SHP2 inhibitor with an IC₅₀ value of 16 nM. SDUY127 binds simultaneously to the tunnel allosteric site and latch allosteric site of SHP2 at a 1:1 stoichiometric ratio, stabilizes the protein in an inactive conformation, and induces sustained inhibition of the MAPK signaling pathway. SDUY127 can be used in research related to leukemia and hepatocellular carcinoma.

SHP844 is a SHP2 inhibitor with the IC₅₀ of 18.9 µM. SHP2 is a protein tyrosine phosphatase (PTP) that regulates tyrosine phosphorylation levels and is involved in cell proliferation, differentiation and survival.

SHP2-IN-40 (Compound 25) is an inhibitor of SHP2 with an AC₅₀ of 0.0107 μM. SHP2-IN-40 can be used in the research of cancer.

Suchilactone (Jatrophan) is a lignan extracted from Monsonia angustifolia E.Mey. Suchilactone binds to SHP2 and inhibits SHP2 activation, thereby inhibiting ERK-mediated cell proliferation. Suchilactone can be ued in acute myeloid leukaemia (AML).

SHP2-IN-47 is a selective and potent SHP2 inhibitor with an IC₅₀ of 0.80 μM. SHP2-IN-47 exhibits potent inhibitory activity against SHP2^E76K (IC₅₀ = 0.37 μM). SHP2-IN-47 functionally inhibits protein tyrosine phosphatase domains and downregulates SHP2-mediated phosphorylation of AKT and ERK. SHP2-IN-47 induces apoptosis and suppresses proliferation of cancer cells. SHP2-IN-47 can be used for the research of cancer, such as acute myelocytic leukemia.

SDUY104 is an orally active amide-based allosteric inhibitor of SHP2 with an IC₅₀ of 140 nM. SDUY104 impairs KRAS-driven pancreatic cancer cell proliferation via cell-cycle arrest and apoptosis. SDUY104 suppresses MAPK signaling and triggers compensatory PI3K-AKT activation. SDUY104 can be used for KRAS-mutant pancreatic cancer research.