Shp2

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

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.

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.

JAB-3068 (SHP2-IN-6) is a potent SHP2 inhibitor exhibiting anticancer and antitumor properties, designed for research in breast, lung, and esophageal cancers.

RMC-4630 (SHP2-IN-7) is an inhibitor of SHP2.

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.

SHP2ATTEC degrader-1 is an ATTEC degrader targeting SHP2, achieving an 83.31% degradation rate in PANC-1 cells at 1.0 μM after 24 hours. It inhibits cell proliferation both in vitro and in vivo. SHP2ATTEC degrader-1 induces apoptosis, elevates the expression of epithelial markers (E-cadherin), and reduces the expression of mesenchymal markers (such as N-cadherin, Vimentin).

SHP2protein degrader-3 is an AUTAC protein degrader specifically targeting SHP2. It induces dose-dependent degradation of SHP2 in HeLa cells, with a DC50 of 3.22 μM, and demonstrates significant antitumor activity with an IC50 of 5.59 μM. The degradation mechanism is mediated via LC3-dependent autophagy, which can be inhibited by lysosomal inhibitors. SHP2protein degrader-3 also induces apoptosis in various tumor cell lines, including cervical cancer cells (HeLa), liver cancer cells (HepG2 and Huh-7), and colon cancer cells (LoVo). [SHP2ligand: ; LC3 Ligand: ; Linker: .]

SHP2 inhibitor LY6 (LY6) is a potent and selective compound that inhibits SHP2 with an IC50 of 9.8 μM, effectively blocking SHP2-mediated cell signaling and proliferation.

SHP2/CDK4-IN-1 (compound 10) is a dual inhibitor targeting SHP2 and CDK4, with oral activity and high potency, showing IC50 values of 4.3 nM for SHP2 and 18.2 nM for CDK4. It induces G0/G1 arrest, inhibits proliferation of TNBC cell lines, and demonstrates significant antitumor efficacy in the EMT6 syngeneic mouse model. This compound is valuable for research into triple-negative breast cancer (TNBC) [1].

SHP2/HDAC-IN-1, a dual allosteric inhibitor targeting SHP2 and HDAC, exhibits potent inhibitory effects with IC 50 values of 20.4 nM (SHP2) and 25.3 nM (HDAC1), respectively. This compound activates T cells, enhances antigen presentation, and promotes cytokine secretion, facilitating efficient antitumor immunity. It holds potential for cancer immunotherapy research.

SHP2 protein degrader-2 (SHP2-D26), a PROTAC degrader targeting the SHP2 protein, effectively reduces its expression across various cancer cell types [1].

SHP2ligand-3 is a PROTAC target protein ligand utilized in the synthesis of SHP2protein degrader-1.

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-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.