Lockdown is a selective, reversible and non-competitive inhibitor of the integrin phosphatase PPM1F (IC50=16.37 uM), blocks cancer cell invasion.Lockdown acts in a dose-dependent, allosteric manner with high selectivity for PPM1F.Lockdown does not inhibit other protein phosphatases (PTP1P, PTPRJ, PP5) in vitro and does not induce additional phenotypes in PPM1F knockout cells.Lockdown fully re-capitulated the phenotype of PPM1F-deficient cells, increased phosphorylation of PPM1F substrates and corruption of integrin-dependent cellular processes in Lockdown treated glioblastoma cells.Phosphatase PPM1F is a regulator of cell adhesion by fine-tuning integrin activity and actin cytoskeleton structures. Elevated expression of this enzyme in human tumors is associated with high invasiveness, enhanced metastasis, and poor prognosis.

NHB1109 is a potent, selective, orally active PTPRD phosphatase inhibitor with IC50 of 0.6 uM, displays selectivity over PTPRS, PTPRF, PTPRJ or PTPN1/PTP1B phosphatases.NHB1109 exhibited no substantial potency at other protein tyrosine phosphatases screened, no significant potency at any of the targets of clinically-useful drugs identified in EUROFINS screens.NHB1109 (200 mg/kg) is well tolerated by mice.NHB1109 is a good candidate to advance to in vivo studies in addiction paradigms and toward human use to reduce reward from addictive substances.

NRT-870-59 is a potent, reversible PTP4A3 inhibitor (IC50=86 nM) with inhibitory specificity for PTP4A3 versus both PTP4A3 A111S mutant and CDC25B.NRT-870-59 does not inhibit CDC25B and PTP4A3 A111S mutant at 1 uM, and 5- to 6-fold less potent aginst DUSP3.NRT-870-59 inhibits PTP4A1, PTP4A2, PTP4A3 mutants C49S, K144I and A106V with IC50 of 133.2, 264.4, 86.0, 332.2, 180.2 and 57.7 nM, respectively.NRT-870-59 inhibits cancer cell colony formation, which is required PTP4A3 expression.The PTP4A (phosphatase of regenerating liver/PRL) phosphatases are a unique subfamily of protein tyrosine phosphatases (PTPs) comprising three highly homologous members (PTP4A1, PTP4A2, and PTP4A3) with 80% amino acid sequence identity.PTP4A3, and to a lesser extent PTP4A1 and PTP4A2, are overexpressed in many types of cancer, promote tumor invasion and dissemination, and contribute to poor patient prognosis.

PF-07284892 (PF 07284892) is a small molecule inhibitor of SHP2 that may block MAPK signaling and lead to tumor growth inhibition.

RMC-4630 is a potent and selective inhibitor of SHP2, a central node in the RAS signaling pathway.

SBI-2130 (SBI 2130) is a novel furanylbenzamide molecule as inhibitor of both WT and oncogenic SHP2 with IC50 of 0.22/5.0 uM for Wt SHP2/SHP2-E76K.

SBI-4668 (SBI 4668) is a novel furanylbenzamide molecule as inhibitor of both WT and oncogenic SHP2 with IC50 of 0.73/1.8 uM for Wt SHP2/SHP2-E76K, 13-fold selective over PTP1B and 73-fold selective over STEP; SBI-4668 exhibited cell viability inhibitory effect on cell growth in both Kasumi-1 cells (IC50=8.5 uM) and KYSE-520 cells (IC50=5.4 uM), SBI-4668 on cell viability was also determined in additional AML cell lines, including MOLM-13 (IC50 = 12 μM) and MV4-11 (IC50 = 8.2 μM). SBI-4668 inhibited U-937 cell (harbor a G60R oncogenic mutation in SHP2) growth with IC50 of 6.3 uM, which is comparable to the potency found in AML cells expressing WT SHP2, while RMC4550 showed a very weak effect on this G60R mutation cell.

SCP1 inhibitor T-62 (T-62) is a specific, small molecule covalent inhibitor of small CTD phosphatase 1 (SCP1), reduces transcription factor REST protein level HEK293 cells.

SCP1 inhibitor T-65 (T-65) is a specific, small molecule covalent inhibitor of small CTD phosphatase 1 (SCP1), reduces transcription factor REST protein level HEK293 cells with EC50 of 1.5 uM.T-65 showed no detectable inhibition against a panel of eight mammalian cysteine-based phosphatases, including SHP2, TCPTP, CD45, DUSP3 and and lymphoid protein tyrosine phosphatase (LYP) at 25 uM.T-65 promotes REST degradation, increases expression of REST-suppressed genes DYRK1a, ELAVL1, USP37, CELSR3, and SCN2 in HEK293 cells.

SMIP-30 is a potent and selective inhibitor of PPM1A with IC50 of 1 uM, selectively inhibits the phosphatase activity of PPM1A.SMIP-30 shows poor inhibitory activity against closest homolog PPM1B (IC50>30 uM).SMIP-30 is an uncompetitive inhibitor for PPM1A (Ki=0.84 uM), does not exhibit any cytotoxic effects up to 30 uM in THP-1 macrophages.SMIP-30 dose-dependently reduces the Mtb burden in infected macrophages, and is well tolerated in vivo and combined with rifampicin reduces Mtb burden in the lungs of infected mice.SMIP-30 induces LC3B-II expression, activates autophagy in Mtb-infected macrophages in a PPM1A-dependent manner.SMIP-30 induces a dose-dependent increase in phosphorylation of S403-p62 in WT macrophages.

TK-453 (TK453) is a potent, selective SHP2 allosteric inhibitor with IC50 of 18.76 and 179 nM for SHP2-WT and SHP2-E76K, respectively.TK-453 has strong inhibitory effect on the enzyme activity of the SHP2-WT, and does not inhibit the activity of the SHP2-PTP catalytic domain, and homologues (SHP1 and PTP1B).TK-453 binds SHP2-WT (KD=150 nM) and SHP2-E76K, higher affinity with SHP2 than SHP099.TK-453 binds in the allosteric binding pocket at the junction of three domains and stabilizes the autoinhibition conformation of SHP2.TK-453 alleviates imiquimod (IMQ)-induced inflammation in macrophages, inhibits the phosphorylation levels of p-IKKα/β and p-p65.TK-453 significantly ameliorates imiquimod-triggered skin-like inflammation in mice via inhibition of IL-23/Th17 axis.

ARL67156 (FPL 67156) triethylamine is a selective ecto-ATPase inhibitor. ARL67156 triethylamine is a competitive inhibitor of NTPDase1 (CD39), NTPDase3 and NPP1, with Kis of 11, 18 and 12 μM, respectively. ARL67156 triethylamine can be used in the research of disease like calcific aortic valve disease, asthma.

Pimecrolimus hydrate (SDZ-ASM 981 hydrate) is a potent, nonsteroid and orally active calcineurin inhibitor. Pimecrolimus hydrate shows anti-inflammatory activity. Pimecrolimus hydrate has the potential for the research of atopic dermatitis and oral erosive lichen planus.

PSB-06126 is a selective nucleoside triphosphate diphosphohydrolase (NTPDase) inhibitor, with the Ki values of 0.33 μM for rat NTPDase 1, 19.1 μM for NTPDase 2 and 2.22 μM for NTPDase 3, respectively.

EWP 815 is a disulfiram analogue, is a potent inhibitor of Ins(1,4)P2 phosphatase and Ins(1,4,5)P3 5-phosphatase. EWP 815 also inhibits enzyme dopamine β-hydroxylase activity.

SPAA-52 is an orally active, competitive and reversible low-molecular-weight protein tyrosine phosphatase (LMW-PTP) inhibitor (IC50=4 nM, Ki=1.2 nM). SPAA-52 can be used in diabete research.

JUN-1111 is an irreversible and selective Cdc25 phosphatase inhibitor with IC50 values of 0.38, 1.8, 0.66, 28, 37 µM for Cdc25A, Cdc25B, Cdc25C, VHR, PTP1B, respectively. JUN-1111 induces cell cycle arrest at G1 and G2/M phases. JUN-1111 decreases the expression of phosphoCdk1.

HKB99 is an allosteric inhibitor of phosphoglycerate mutase 1 (PGAM1). HKB99 inhibits the formation of invasive pseudopodia and increases the level of PAI-2 in vitro. HKB99 increases the oxidative stress, activates JNK/c-Jun and suppresses AKT and ERK. HKB99 can be used for the research of non-small-cell lung cancer (NSCLC).

ATUX-1215 is a direct, orally active small molecule activator of protein phosphatase 2A (PP2A), suppresses bleomycin-induced fibrosis in vivo.

ATUX-792 is a small molecule activator of protein phosphatase 2A (PP2A), decreases survival, proliferation, and motility of neuroblastoma in vitro and tumor growth in vivo.

CNBCA is a selective, competitive inhibitor of Src homology phosphotyrosyl phosphatase 2 (SHP2) with IC50 of 0.87 uM, effectively suppresses breast cancer cell phenotypes.

DS-1211 (DS1211) is a potent, selecitve inhibitor of tissue-nonspecific alkaline phosphatase (TNAP) with IC50 of 3.4 nM.