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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

CHIR-98023 is a potent, selective and reversible inhibitor of GSK3, with IC50s of 10 nM and 6.7 nM for GSK3α and GSK3β, respectively. CHIR-98023 can improve insulin action and glucose metabolism.

SKL2001 is an agonist of the Wnt/β-catenin pathway, with anti-cancer activity.

Foxy-5 is a novel Wnt-5A mimicking hexapeptide that inhibits breast cancer metastasis in vivo by targeting cell motility.

Casein Kinase inhibitor A51 (CKIα inhibitor A51) is a novel pan-specific CKI (CSNK1) inhibitor (Kd=0.5-20 nM, CKIα Kd=5.3 nM) that co-targets the transcriptional kinases CDK7 and CDK9, with hardly inhibition of CDK8, CDK13, CDK11a, CDK11b, and CDK19; target both CDK7 and CDK9 with low nM Kd values; induces leukemia cell apoptosis at <160 nM, in correlation to the capacity to stabilize p53; shows high and selective sensitivity against leukemic CFUs in colony-forming unit (CFU) assay, without effect on normal hematopoietic CFUs; blocking CKIα together with CDK7 and/or CDK9 synergistically stabilize p53, deprive leukemia cells of survival and proliferation-maintaining SE-driven oncogenes, induce apoptosis, abolishes the expression of MYC, MDM2, and the anti-apoptotic oncogene MCL1; demonstrates therapeutic efficacy with preserved hematopoiesis and leukemia cure potential in AML mouse models.

CB-103 is a notch signaling pathway inhibitor extracted from patent US9296682B2. CB-103 is developed for the treatment of cancers.

SANT 2 is a potent antagonist of Hh-signaling pathway. Hedgehog (Hh) signaling plays an important role in cell signaling of embryonic development and adult tissue homeostasis. SANT 2 has the potential for the research of several malignancies including Gorlin syndrome (a disorder predisposing to basal cell carcinoma, medulloblastoma and rhabdomyosarcoma), prostate, pancreatic and breast cancers.

KY-02327 acetate, a metabolically stabilized KY-02061 analog, is a potent Dishevelled (Dvl)-CXXC5 interaction inhibitor. KY-02327 acetate shows an activating effect on the Wnt/β-catenin pathway, resulting in promotion of osteoblast differentiation.

(E/Z)-BIO-acetoxime (GSK-3 Inhibitor X) is a potent and selective GSK-3α/β inhibitor, with an IC50 of 10 nM. (E/Z)-BIO-acetoxime shows more than 200-flod selectivity over CDK5/p25, CDK2/cyclin A and CDK1/cyclin B (IC50=2.4, 4.3, 63 μM).

Carboxylesterase-IN-2 (compound 4u) is a potent inhibitor of Carboxylesterase Notum with an IC50 less than or equal to 10 nM. Notum is a negative regulator of Wnt signaling acting through the hydrolysis of a palmitoleoylate ester, which is required for Wnt activity. Carboxylesterase-IN-2 has the potential for the research of cancer disease.

Carboxylesterase-IN-3 (compound 4y) is a potent inhibitor of Carboxylesterase Notum with an IC50 less than or equal to 10 nM. Notum is a negative regulator of Wnt signaling acting through the hydrolysis of a palmitoleoylate ester, which is required for Wnt activity. Carboxylesterase-IN-3 has the potential for the research of cancer disease.

ZLDI-8 (IAC-8) is a novel Notch signaling pathway inhibitor for Notch activating/cleaving enzyme ADAM-17, significantly decreases the level of NICD and accumulation of NICD in the nucleus; exhibits cytotoxic acitviity against MHCC97-H cells with IC50 of 5.32 uM, reduces the expression of pro-survival/anti-apoptosis regulators, Survivin and cIAP1/2, also increases the expression of epithelial marker E-Cadherin and reduces mesenchymal markers N-Cadherin and Vimentin in HCC cells; significantly disrupted the activity of Notch pathway in HCC cells and inhibits the epithelial-mesenchymal transition (EMT) process of HCC cells; ZLDI-8 treatment enhances the susceptibility of HCC cells to Sorafenib, Etoposide, and Paclitaxel both in vitro and in vivo.

HLY78 is an activator of the Wnt/β-catenin signaling pathway, which targets the DIX domain of Axin and potentiates the Axin-LRP6 association to promote Wnt signaling transduction[1].

Bikinin is a strong activator of brassinosteroid (BR) signaling.

γ-Secretase modulator 10 is a novel γ-secretase modulator.

Ciliobrevin A(HPI-4) is a Hedgehog pathway inhibitor and ciliogenesis inhibitor.

CP21R7 is a potent and selective GSK-3β inhibitor.

Semagacestat (LY450139) is a γ-secretase blocker for Aβ42, Aβ40 and Aβ38 with IC50 of 10.9 nM, 12.1 nM and 12.0 nM, also inhibits Notch signaling with IC50 of 14.1 nM.

ICG-001 is a small-molecule antagonist of b-catenin/TCF-mediated transcription (IC50 = 3 uM) and specifically downregulates the expression of a subset of b-catenin/TCF-responsive genes. ICG-001 binds specifically to cyclic AMP response element-binding pro

iCRT3 is an inhibitor of both Wnt and β-catenin-responsive transcription.