Shp1

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.

SHP1705 is a potent and selective activator of Cryptochrome 2 (CRY2). It inhibits BMAL1-CLOCK transcriptional activity and significantly enhances its efficacy against glioblastoma stem cells (GSC) and patient-derived xenograft (PDX) tumors. SHP1705 can be utilized in studies of the biological characteristics of GSCs and the survival of glioblastoma (GBM).

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].

NSC-87877 disodium (NSC87877) is a cell-permeable inhibitor of both SHP-1 and SHP-2 with IC50 values of 355 and 318 nM respectively. It also inhibits EGF-induced Erk1/2 activation in HEK293 cells and significantly reduces MDA-MB-468 cell viability/proliferation.

Compound SC-1 is a a derivative of the multiple tyrosine kinase inhibitor sorafenib. Compound SC-1 potently inhibits the phosphorylation of STAT3 by blocking STAT3 phosphorylation and activation, and induces apoptosis in hepatocellular carcinoma cell lines[1].

SC-43 is a potent and orally active agonist of SHP-1 (PTPN6). SC-43 inhibits the phosphorylation of STAT3 and induces cell apoptosis, and with anti-fibrotic and anticancer effects.

BPDA2 is a highly selective and competitive SHP2 inhibitor, exhibiting IC50 values of 92.0 nM for SHP2, and 33.39 μM and 40.71 μM for SHP1 and SHP1B, respectively. This compound effectively downregulates mitogenic and cell survival signaling, including reducing expression of receptor tyrosine kinases (RTKs). Furthermore, BPDA2 suppresses SHP2-mediated signaling, leading to the inhibition of breast cancer cell phenotypes [1].

2-Bromo-4'-hydroxyacetophenone(PTP Inhibitor I) is a cell-permeable, protein tyrosine phosphatase (PTP) inhibitor that covalently blocks the catalytic domain of the Src homology region 2 domain-containing phosphatase (SHP-1(ΔSH2)) with a Ki value of 43 μM and PTP1B with a Ki value of 42 μM [1]. SHP-1 and PTP1B both have known roles in regulating insulin signaling as well as myeloid and lymphoid cell differentiation, making inhibitors of these phosphatases of interest in diabetes, cancer, allergy, and inflammation research [2].

PTP inhibitor 1 is an inhibitor of cell-permeable protein tyrosine phosphatase (PTP) that covalently binds the catalytic domain of the Src homology region 2 domain-containing phosphatase (SHP-1(ΔSH2)),with Ki of128 μM.

NSC-87877 is an effective inhibitor of Shp2 and Shp1 protein tyrosine phosphatases (IC50=0.318 μM, 0.355 μM of shp2 and shp1, respectively).It also inhibits dual-specificity phosphatase 26 (DUSP26).

PHPS1 sodium is a potent and selective inhibitor of Shp2, with Kis of 0.73, 5.8, 10.7, 5.8, and 0.47 μM for Shp2, Shp2-R362K, Shp1, PTP1B, and PTP1B-Q, respectively [1].

Darinaparsin is a dimethylated arsenic linked to glutathione. It is cytotoxic to DU145, LNCaP, and PC3 prostate cancer cells (IC50s = 5-10 µM) and patient-derived primary prostate cancer cells (IC50s = 2.5-20 µM), as well as Jurkat T cell lymphoma and L540 Hodgkin lymphoma cells (IC50s = 2.7 and 1.3 µM, respectively). [1][2] It decreases the tumor-initiating subpopulation in DU145 and PC3 cells and halts the cell cycle in the G2/M phase. Darinaparsin decreases transcription of Gli-2, a transcription factor that mediates Sonic hedgehog signaling, when used at a concentration of 1.5 but not 3 µM. It decreases SHP1 phosphatase activity and increases ERK phosphorylation. [2] Darinaparsin reduces tumor growth in DU145 and PC3 prostate cancer mouse xenograft models when administered at a dose of 100 mg/kg every other day.[1]

LYP-IN-1 is a potent and highly selective inhibitor of lymphoid-specific tyrosine phosphatase (LYP), with a Ki value of 110 nM and an IC50 of 0.259 μM. LYP-IN-1 exhibits additional selectivity against a broad range of PTPs, including SHP1 (IC50 = 5 μM) and SHP2 (IC50 = 2.5 μM). LYP-IN-1 demonstrates strong efficacy in both T cells and mast cells, making it a valuable compound for research into autoimmune disorders and immune signaling pathways.

GS-493, a highly specific protein tyrosine phosphatase SHP2 (PTPN11) inhibitor, exhibits remarkable potency with an IC50 of 71 nM. It displays 29- and 45-fold greater affinity towards SHP2 compared to its related counterparts, SHP1 and PTP1B, respectively. In addition, GS-493 impedes both cellular motility and growth of cancer cells, portraying promising antitumor effects.

TPI-1 is a SHP-1 inhibitor.

SPI--112Me, a prodrug of SPI-112, preferentially inhibits the PTPase activity of Shp2 over Shp1 and PTP1B by more than 20-fold in cell-free assays.

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].

Cryptosporioptide A (Compound 3), a protein tyrosine phosphatase inhibitor, originates from the insect-parasitic fungus Cordyceps gracilioides. This compound effectively inhibits several enzymes including PTP1B, SHP2, CDC25B, LAR, and SHP1 with respective IC50 values of 7.3, 5.7, 7.6, >50, and 4.9 μg/mL [1].

SHP2-IN-31 is an SHP2 inhibitor with an IC50 value of 13 nM (wild-type SHP2), >10000 nM (SHP1), and >10000 nM (SHP2 E76K). This compound effectively inhibits pERK in a variety of tumor cells and suppresses tumor growth in xenograft models driven by RTK/KRAS.

Sydowimide A is an effective inhibitor of phosphatase 1 containing the Src homology 2 domain (SHP1), T cell protein tyrosine phosphatase (TCPTP), and leukocyte common antigen (CD45) with IC50 values of 1.5, 2.4, and 18.83 μM, respectively.