ASR-490 reduces the viability of HCT116 and SW620 cells by downregulating Notch1 signaling. ASR-490 overcomes Notch1 overexpression and inhibits the growth of HCT/Notch1 transfectants. ASR-490 inhibits the tumor growth in control (pCMV/HCT116) and Notch1/HCT116 in xenotransplanted mice.

BT-GSI is a γ-secretase inhibitor (GSI) and a bone-targeted Notch inhibitor. BT-GSI has dual anti-myeloma and anti-resorptive properties, which can be used for the research of multiple myeloma and associated bone disease. BT-GSI inhibits tumor growth and osteolytic disease progression.

MRT-14 is a potent antagonist of Smo. Smo is the major component involved in signal transduction of the Hedgehog (Hh) morphogens. MRT-14 has the potential for the research of several types of cancers linked to abnormal Hh signaling.

An anthelmintic effective agent for pinworms that shows to be a potent inhibitor of Wnt signaling with EC50 of 10 nM; binds to all CK1 family members in vitro at low nanomolar concentrations and selectively potentiates CK1α kinase activity; inhibits Wnt signaling downstream of β-catenin, and promotes Pygopus degradation; also is a potent inhibitor of HH signaling by reducing the stability of the Gli family of transcription factors.

ASR490 (ASR 490) is a small molecule that binds to NRR of Notch1, specifically inhibits Notch1-mediated survival of colorectal cancer cells (IC50=0.6-1.2 uM); ASR490 overcomes Notch1 overexpression and inhibits the growth of HCT/Notch1 transfectants, reduces Notch1-mediated tumor burden in xenografts.

Autotaxin-IN-13 ( ATX-i) is a highly potent, selective Autotaxin inhibitor with IC50 of 6 nM.Autotaxin showed sufficient oral bioavailability and low plasma clearance in vivo as well as a suitable half-life to allow for bid or food admix dosing.

CAD204520 (CAD 204520) is a potent, specific, oral available inhibitor of SERCA (Sarco/Endoplasmic Reticulum Calcium ATPase) with IC50 of 0.34 uM; CAD204520 preferentially targets mutated over wild-type NOTCH1 proteins in T-All and MCL. CAD204520 preferentially inhibited the Ca2+-ATPase by reducing SERCA's ATP hydrolysis activity with an IC50=0.34 uM as compared to the Na+/K+-ATPase (IC50 8.30 uM) and the H+-ATPase. CAD204520 modulates Notch1 signaling, and preferentially inhibits NOTCH1 mutated cancers. CAD204520 suppresses NOTCH1-mutated leukemic cells in a T-ALL xenografted model without causing cardiac toxicity.

CGX1321 (CGX-1321) is a nove potent and specific inhibitor of porcupine (PORCN) that inhibits Wnt pathway, block secretion of WNT proteins with IC50 of 1 nM; CGX1321 displayed >500 times selective for Porcupine over the most related target enzyme, hedgehog acyltransferase. CGX1321 increased Ki67+ and phosphohistone H3 (PH3+) cardiomyocytes in culture, up-regulated cell cycle regulating genes such as Ccnb1 and Ccne1, did not alter YAP protein phosphorylation and nuclear translocation in cardiomyocytes. CGX1321 administration blocked the secretion of Wnt proteins, and inhibited both canonical and non-canonical Wnt signaling pathways in MI injury mice. CGX1321 improved cardiac function, reduced myocardial infarct size, and fibrosis of post-MI hearts. CGX1321 significantly increased newly formed cardiomyocytes in infarct border zone of post-MI hearts, evidenced by the increased EdU+ cardiomyocytes.

CIGB-300 (P15-Tat) is a cell-permeable cyclic peptide that modulates CK2 (CSNK2) activity by binding to the phosphoacceptor site on CK2 targets, abrogates the CK2 phosphorylation by blocking recombinant substrates in vitro.CIGB-300 (P15-Tat) induced apoptosis as evidenced by rapid caspase activation and cellular cytotoxicity in a variety of tumor cell lines (HSCLC H-82 cell IC50=20 uM).CIGB-300 (P15-Tat) demonstrated substantial regression of the tumor mass C57BL6 mice bearing day 7-established solid tumors.CIGB-300 (P15-Tat) reduced breast cancer cell growth in MDA-MB-231, MCF-7 and F3II cells, exerting a pro-apoptotic action and cell cycle arrest. CIGB-300 decreased cell adhesion, migration and clonogenic capacity of malignant cells.CIGB-300 may interfere with the SARS-CoV-2 life cycle within infected human cells.

CK2 inhibitor KN2 is a potent, highly selective, cell-permeable, bivalent CK2 inhibitor, binds to CK2α- and CK2α′-based CK2 holoenzymes with Ki of 6.1 nM (CK2α2β2) and 4.0 nM (CK2α′2β2).KN2 inhibits CK2α- and CK2α′-based CK2 holoenzymes with IC50 of 19.3 nM (CK2α2β2) and 15.6 nM (CK2α′2β2) at 100 uM ATP.KN2 downregulated the CK2-dependent phosphorylation level of Akt phosphorylation at Ser129 (p-Akt S129).

COB-187 (COB187) is a highly potent and selective inhibitor of GSK-3 with IC50 of 22/11 nM against GSK-3α/GSK-3β.COB-187 inhibits GSK-3 phosphorylation of β-catenin and, albeit to a lesser extent, glycogen synthase.COB-187 increases the protein level of β-catenin in RAW 264.7 macrophages.COB-187 enhances β-catenin localization to the perinuclear and nuclear region in THP-1 macrophage, does not change the β-catenin mRNA level.COB-187 significantly increases the expression of the Wnt target gene cyclin D1, reduces the phosphorylation of tau in HEK293 cells transfected with tau expression vector.COB-187 inhibits only 3 kinases at >40% in a panel of 414 kinase assays, more selective relative to Tideglusib.

E722-2648 (Compound C-1) is a novel specific and competitive small molecule β-catenin/BCL9 interaction inhibitor with ITC KD of 1.05 uM and IC50 of 9 uM, blocks oncogenic Wnt signaling and disrupts cholesterol homeostasis in colorectal cancer.E722-2648 (Compound C-1) inhibited β-catenin/BCL9 complexes at concentrations as low as 1 uM in BCL9-dependent CRC cell lines, Colo320 and HCT116.E722-2648 (Compound C-1) inhibited the expression of bona fide downstream Wnt/β-catenin target genes, AXIN2 and CD44, in the β-catenin/BCL9-dependent CRC cell lines.E722-2648 (Compound C-1) disrupted cholesterol homeostasis via increased cholesterol esterification and lipid droplet accumulation.E722-2648 (Compound C-1) demonstrated antitumorigenic activity in CRC cell lines and xenograft mouse models.

Frizzled6 agonist SAG1.3 is a small molecule SMO agonist that targets Frizzled6 (FZD6) as a partial agonist with limited subtype selectivity; Frizzled6 agonist SAG1.3 binds FZD6 and evokes a conformational change reminiscent of that seen in other agonist-bound GPCRs. In competition experiments, increasing concentrations of unlabeled SAG1.3 decreased BODIPY-cyclopamine (300 nM) binding to Nluc-FZD6 in a concentration-dependent manner (pKi=5.6). SAG1.3 mediates recruitment of mGsi proteins to FZD6 and induces conformational changes in FZD6, induces FZD6-dependent dissociation of heterotrimeric Gi and phosphorylation of ERK1/2, and modifies the interactions between FZD6 and DVL2.

GA-017 (GA017) is a potent, selective, ATP-competitive LATS kinase (LATS1/2) inhibitor with IC50 of 4.10/3.92 nM, respectively, promotes cell growth.GA-017 increases the number and size of spheroids of various cell-types in both scaffold-based and scaffold-independent cultures.GA-017 also enhances the ex vivo formation of mouse intestinal organoids.GA-017 facilitates the growth of spheroids and organoids by stabilizing and translocating YAP/TAZ into the cell nucleus.GA-017 inhibits the Hippo pathway to promote YAP/TAZ stabilization and nuclear translocation.GA-017 induces expression of Hippo pathway-related genes such as ANKRD1, CYR61, and CTGF in SKOV3 cells in a time- and dose-dependent manner.GA-017 inhibited the activity of 16 kinases of the AGC family at 100 nM against a panel of 321 diverse kinases.The serine/threonine protein kinases LATS (LATS1/2) phosphorylate YAP/TAZ, key effectors of the growth- and proliferation-regulating Hippo signaling pathway.

GB1874 is an inhibitor of the Wnt pathway that targets the β-catenin-TCF4 interaction.GB1874 affected the proliferation and stemness of Wnt-addicted colorectal cancer (CRC) cells in vitro.GB1874 inhibited the growth of CRC tumor xenografts in vivo.

GSK3β-IN-1a is a relatively selective and potent GSK-3β inhibitor with IC50 of 64 nM; induces replication of growth-arrested R7T1 β cells in a dose-dependent manner with EC50 of 1.1 uM, likely mediates β-cell proliferation through the Wnt signaling pathway.

KY19334 is a specific small molecule inhibitor of CXXC5-Dishevelled (Dvl) protein-protein interaction (PPI), restores the Wnt/β‐catenin signalling.KY19334 reverses obesity‐related metabolic diseases with adult tissue remodelling.Oral administration of KY19334 (25 mg/kg) suppressed fasting glucose levels improves obesity‐related insulin resistance with long‐lasting effect in HFD‐fed mice.KY19334 treatment improves hepatic glucose homeostasis. KY19334 enhances energy expenditure by increasing the thermogenic activity of beige‐fat tissues.KY19334 treatment restores β‐cell mass and functions in HFD‐fed and STZ‐induced diabetes mellitus (DM) mice.

NADI-351 is a specific small-molecule inhibitor of Notch1 transcriptional complexes with IC50 of 8.8 uM in cellualr reporter assays.NADI-351 inhibited OE33 cell growth in single dose MTT assays (EC50= 10 uM) and, more potently, in multi-dose colony formation assays (EC50=1.3 uM)NADI-351 is 15 times more potent than IMR-1 in an NTC AlphaScreen assay.NADI-351 selectively disrupted Notch1 transcription complexes, inhibited recruitment of Notch1 to the NTC (Notch Ternary Complex) and to the HES1 promoter, and reduced Notch1 recruitment to target genes.NADI-351 inhibits tumor growth in Notch-dependent cancers and does not exert gastrointestinal toxicity associated with goblet cell metaplasia.NADI-351 selectively inhibits stem-like esophageal adenocarcinoma (EAC) cell populations.

Rhonin is a first small-molecule ligand of the RHO GDP-dissociation inhibitor 1 (RHOGDI1), binds to RHOGDI (Ki=2.2 uM), is an inhibitor of Hh-induced osteogenesis.Rhonin interferes with its function by disrupting the interaction between RHOGDI and RHO GTPases.Rhonin alters the subcellular localization of RHO GTPases.Rhonin inhibited RHOGDI1-mediated extraction of RAC1 from liposomes, Rhonin increased the levels of GTP-bound RHO GTPases, did not alter the total levels of the three RHO GTPasesRhonin an inhibitor of Hh-induced osteogenesis, but does not efficiently target canonical Hh signaling and SMO, directly targets RHOGDI, impairs RHOGDI function.

TEAD-IN-2 (TEAD antagonist 2) is a small molecule TEAD antagonist (TEAD2 IC50=603 nM FP assays, SPR Kd=229 nM) that binds the TEAD lipid pocket and disrupts TEAD S-palmitoylation; TEAD-IN-2 showed similar IC50 against all TEAD paralogs TEAD1, TEAD3, and TEAD4 both in IP and SRP assays. TEAD-IN-2 disrupted Hippo signaling in a Detroit X1 562 cell reporter assay with IC50 of 31.8 nM, with no significant cytotoxicity indications in either primary human hepatocytes or human liver microtissues at 100 uM. The inhibition of TEAD activity via TEAD-IN-2 was not due to the inability of TEAD to form a complex with YAP in cells. TEAD-IN-2 functioned by acting as a TEAD S-palmitoylation mimic, binding and stabilizing newly translated TEAD proteins, TEAD-palmitoylation-deficient mutant K357A caused a stronger rescue of TEAD expression in HEK293T cells transfected TEAD2-K357A. Dysregulating TEAD S-palmitoylation via TEAD-IN-2 could effectively inhibit Hippo-dependent tumor growth in vivo.

VT02484 is the negative control compound of VT02956, which is a highly potent Hippo pathway kinase LATS inhibitor.

VT02956 is a potent, specific inhibitor of Hippo pathway kinase LATS with IC50 of 0.76 nM (LATS1) and 0.52 nM (LATS2), respectively; VT02956 reduces YAP/TAZ phosphorylation in both dose- and time-dependent manner with IC50 of 0.16 μM and 0.43 μM in HEK293A cells and 4T1 cells, respectively. VT02956 suppresses ESR1 transcription, dramaticly reduces ERα and its target genes TFF1 and GREB1. VT02956 targets the LATS-YAP/TAZ-ERα axis to inhibit ER+ tumours cell growth, inhibits the proliferation of MCF-7 and T47D cells. VT02956 inhibits the growth of T47D cells with hormone therapy resistant ESR1 mutation (ERa Y537S or D538G), enhances the anti-tumour effect of palbociclib in ER+ breast cancer cells.