shp2

Bis(maltolato)oxovanadium(IV) (BMOV) is a potent, reversible, competitive, and orally active pan-PTP (protein tyrosine phosphatases) inhibitor with insulin-mimicking effects and anti-diabetic properties. BMOV is a potent insulin sensitizer and has been shown to improve cardiac dysfunctions in diabetic models. BMOV inhibits HCPTPA, PTP1B, HPTPβ, and SHP2 with IC50s of 126 nM, 109 nM, 26 nM, and 201 nM, respectively [1][2].

TNO155 is a protein tyrosine phosphatase (PTP) non-receptor type 11 (SHP2; src homology region 2 domain phosphatase; PTPN11) inhibitor(IC50 : 0.011 µM),with potential antineoplastic activity.

RMC-4550 is an effective and allosteric inhibitor of SHP2 (IC50: 0.583 nM).

SHP394 is an orally efficacious inhibitor of protein tyrosine phosphatase SHP2 (IC50: 23 nM).

SHP836 is an inhibitor of SHP2 allosteric (IC50: 12 μM for the full-length SHP2).

PHPS1 is an inhibitor of Shp2. PHPS1 efficiently inhibits activation of Erk1/2 by the leukemia-associated Shp2 mutant, Shp2-E76K, and blocks the anchorage-independent growth of a variety of human tumor cell lines.

SPI-112, the SPI-112 methyl ester analog, can inhibit cellular Shp2 PTP activity. SPI-112 bound to Shp2 by surface plasmon resonance (SPR) and displayed competitive inhibitor kinetics to Shp2.

IACS-13909 (BBP-398), a specific and potent allosteric inhibitor of SHP2, that suppresses signaling through the MAPK pathway.

SHP2 IN-1 is an allergic SHP2 (PTPN11) inhibitor(IC50 : 3 nM).

SHP2-IN-32 (compound C6) is an orally effective allosteric SHP2 inhibitor with an IC50 value of 0.13 nM. It demonstrates antitumor activity.

SHP2 inhibitor CNBDA is a novel SHP2 inhibitor with an IC50 value of 5 μM, demonstrating significant efficacy against breast cancer cells.

SHP2-IN-33 (Compound D13) is an allosteric inhibitor of SHP2, exhibiting an IC50 of 1.2 μM against SHP2. It demonstrates an antiproliferative IC50 of 38 μM in Huh7 cells by blocking the G0 G1 cell cycle, inducing apoptosis (Apoptosis), and inhibiting the MAPK signaling pathway. In a Huh7 xenograft mouse model, SHP2-IN-33 shows significant antitumor activity and favorable pharmacokinetic properties, including 54% oral bioavailability and a half-life of 10.57 hours. SHP2-IN-33 holds potential for research involving SHP2-associated tumor diseases.

SHP2-IN-34 (compound A8) is a phenylurea SHP2 inhibitor with anti-cancer properties. It significantly suppresses tumor growth in CT26 mouse models.

SHP2-IN-35 (Compound 3f) functions as an inhibitor of SHP2. It exhibits antiproliferative activity in cancer cell lines RKO, SW480, and CT26, with IC50 values of 5.72 μM, 3.71 μM, and 1.42 μM, respectively. SHP2-IN-35 inhibits the PI3K-Akt signaling pathway, regulates the expression of cell cycle-related genes, and induces mitochondrial autophagy (autophagy). Within the tumor microenvironment (TME), SHP2-IN-35 suppresses the expression of certain cytokines and chemokines, thereby modulating tumor progression.

SHP2-IN-36 (Compound B8) is an allosteric inhibitor of SHP2 with an IC50 of 9.0 nM, and it exhibits an IC50 of 40 nM against p-ERK. Moreover, SHP2-IN-36 demonstrates significant antitumor activity in the KYSE520 xenograft mouse model and is applicable for research in the field of antitumor studies.

SHP2-IN-37 (compound C5) is a potent allosteric inhibitor selective for SHP2, with an IC50 of 0.023 μM. It exhibits antiproliferative effects on KYSE-520 and MV-411 cells, with IC50 values of 6.97 μM and 0.67 μM, respectively.

SHP2-IN-24 (compound 111675) is a potent inhibitor of SHP2, with an IC50 of 0.878 µM and a Ki of 0.118 µM.

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

SHP2-IN-25 (Compound 6) is an allosteric inhibitor of SHP2, with an IC50 of 225 nM, and is applicable in cancer research.

SHP2-IN-28 (Compound 7188-0011) is an inhibitor of Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) with an IC50 of 54.31 μM. It exerts its inhibitory effect by binding to the allosteric site of SHP2, displaying high selectivity.

SHP2-IN-6 hydrochloride is a highly potent inhibitor of SHP2 with an IC50 of 25.8 nM.

SHP2-D26 is a highly potent and effective SHP2 degrader. Its mechanism of action involves the induction of SHP2 degradation through binding to VHL-1 and SHP2 proteins. Additionally, the degradation of SHP2 induced by SHP2-D26 is dependent on neddylation and proteasome activity.

SHP2-IN-9 is a potent inhibitor (IC50 = 1.174 μM) specifically targeting the SHP2 protein, displaying improved penetration across the blood-brain barrier. It exhibits a remarkable 85-fold selectivity for SHP2 over SHP1. By inhibiting SHP2-mediated cell signal transduction and impairing cancer cell proliferation, SHP2-IN-9 effectively suppresses the growth of both cervix cancer tumors and glioblastoma in vivo [1].

SHP2-IN-8 is a reversible, noncompetitive, selective and efficient allosteric SHP2 inhibitor (IC50=23 nM, Ki=22 nM), which also has effects in cells. SHP2-IN-8 can cause significant thermal displacement( Δ Tm = 7.01 ℃). SHP2-IN-8 can inhibit the phosphorylation of AKT and induce apoptosis of Hela cells.