Stem Cells/Wnt

TFMB-(S)-2-HG is a potent inhibitor of TET2 and EglN prolyl hydroxylases. It downregulates Wnt3a and intranuclear β-catenin protein expression, and inhibits osteogenic differentiation of cells. TFMB-(S)-2-HG shows potential for research in acute myeloid leukemia (AML).

Zamaporvint (RXC004) is an orally active and selective Wnt pathway inhibitor that targets the membrane-bound O-acyltransferase Porcupine. By inhibiting Wnt ligand palmitoylation, it blocks Wnt ligand secretion and downstream pathway activation. Zamaporvint exhibits a favorable pharmacokinetic profile and shows potent antiproliferative activity in Wnt ligand-dependent colorectal and pancreatic cancer cell lines. With multiple antitumor mechanisms, it is a promising agent for cancer research.

α-Amyrin is an orally active pentacyclic triterpenoid that activates the ERK and GSK-3β signaling pathways. It is studied for its potential in treating metabolic syndrome induced by a high-fructose diet and cognitive dysfunction associated with reduced cholinergic neurotransmission.

TMCB (CK2/ERK8-IN-1) is a dual inhibitor of casein kinase 2 (CK2) and ERK8 (MAPK15/ERK7), with a Ki of 0.25 µM for CK2 and IC50 values of 0.50 µM for both targets. It also exhibits binding affinity for PIM1 (Ki = 8.65 µM), HIPK2 (Ki = 15.25 µM), and DYRK1A (Ki = 11.9 µM). CK2/ERK8-IN-1 demonstrates pro-apoptotic activity and is a useful tool for studying kinase-mediated cell survival pathways.

Withanolide B, a bioactive constituent of *Withania somnifera* Dunal, promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) through activation of the ERK1/2 and Wnt/β-catenin signaling pathways. It also demonstrates neuroprotective, anti-arthritic, anti-aging, and anti-cancer properties.

Penehyclidine hydrochloride (also known as Penequinine hydrochloride) is a selective anticholinergic agent that acts as an antagonist of muscarinic M1 and M3 receptors. It exerts anti-inflammatory effects by modulating immune signaling in lung tissue, notably through activation of the NF-κB pathway and inhibition of pro-inflammatory cytokine release. In preclinical studies, Penehyclidine hydrochloride has been shown to alleviate pulmonary inflammation in rat models of chronic obstructive pulmonary disease (COPD), particularly under conditions of mechanical ventilation. These properties suggest its potential utility in managing respiratory inflammatory conditions and improving outcomes in mechanically ventilated patients with COPD.

PROTAC YAP degrader-1 (compound YZ-6) is a bifunctional molecule designed to selectively degrade Yes-associated protein (YAP), a key effector of the Hippo signaling pathway involved in cell proliferation, survival, and tumorigenesis. In addition to promoting proteasomal degradation of YAP, it also inhibits YAP's nuclear localization, thereby impairing its transcriptional co-activator functions.YZ-6 is composed of two main components:Target protein ligand: NSC682769 and E3 ubiquitin ligase recruiter with linker: (R,S,R)-AHPC-PEG2-C2-Boc which recruits the VHL E3 ligase complex. The linker used in the PROTAC design is Acid-PEG2-C2-Boc, facilitating optimal spatial orientation for ternary complex formation. The demethylated analog Demethyl-NSC682769 serves as a target ligand activity control. PROTAC YAP degrader-1 represents a novel tool for functional YAP inhibition and offers potential therapeutic applications in YAP-driven cancers and fibrotic diseases.

TMX-4116 is a selective degrader of casein kinase 1α (CK1α), demonstrating preferential degradation activity with DC₅₀ values below 200 nM in MOLT4, Jurkat, and MM.1S cell lines. By targeting CK1α for proteasomal degradation, TMX-4116 offers a promising tool for investigating CK1α function and holds potential for therapeutic research in multiple myeloma and related hematologic malignancies.

SJ3149 is a selective and potent molecular glue degrader that targets casein kinase 1α (CK1α) for proteasomal degradation. By promoting CK1α elimination, SJ3149 exhibits broad antiproliferative activity across various cancer models. It serves as a valuable tool for exploring CK1α-dependent signaling pathways and holds promise for therapeutic development in oncology research.

HS-276 is an orally bioavailable, potent, and highly selective inhibitor of transforming growth factor-β–activated kinase 1 (TAK1), with a Kᵢ of 2.5 nM. It exhibits strong inhibition of TAK1 and moderate activity against a panel of other kinases, including CLK2, GCK, ULK2, MAP4K5, IRAK1, NUAK, CSNK1G2, CAMKKβ-1, and MLK1, with respective IC₅₀ values ranging from 8.25 to 5585 nM. HS-276 is a valuable tool for investigating TAK1-mediated signaling pathways and holds therapeutic potential for inflammatory conditions such as rheumatoid arthritis (RA).

SGC-CK2-1 is a highly potent, ATP-competitive, and cell-permeable chemical probe that selectively targets casein kinase 2 (CK2), exhibiting IC₅₀ values of 36 nM for CK2α and 16 nM for CK2α′ in the nanoBRET assay. With exclusive selectivity for both human CK2 isoforms, SGC-CK2-1 serves as a valuable tool for studying CK2-related signaling pathways and holds potential for research in neurodegenerative diseases.

SSTC3 is a potent activator of casein kinase 1α (CK1α), with a binding affinity (K_d) of 32 nM, and functions as an inhibitor of WNT/β-catenin signaling with an EC₅₀ of 30 nM. Unlike many conventional WNT pathway inhibitors, SSTC3 demonstrates minimal gastrointestinal toxicity, offering a promising therapeutic strategy for targeting WNT-driven cancers with improved safety profiles.

BTX-A51 (Casein Kinase Inhibitor A51) is a potent, orally bioavailable inhibitor of casein kinase 1α (CK1α). It effectively induces apoptosis in leukemia cells and demonstrates strong anti-leukemic activity in preclinical models, making it a promising therapeutic candidate for hematologic malignancies.

FPFT-2216 is a “molecular glue” degrader that facilitates the proteasomal degradation of multiple target proteins, including phosphodiesterase 6D (PDE6D), zinc finger transcription factors Ikaros (IKZF1) and Aiolos (IKZF3), as well as casein kinase 1α (CK1α). By promoting selective ubiquitination through E3 ligase recruitment, FPFT-2216 modulates key regulatory pathways and holds promise for research in oncology and inflammatory diseases.

xStAx-VHLL is a PROTAC degrader targeting β-catenin, promoting its ubiquitination and proteasomal degradation. It effectively inhibits the Wnt/β-catenin signaling pathway and suppresses proliferation of colon cancer cells, demonstrating anti-tumor activity.

CCT036477 is a selective inhibitor of the Wnt/β-catenin signaling pathway that effectively disrupts β-catenin-mediated transcription without affecting its overall levels. This compound demonstrates significant anti-proliferative effects on various cancer cell lines and impairs embryonic development. Additionally, CCT036477 downregulates the expression of key Wnt target genes, including PPARδ, Cyclin D1, TCF4, and ID2, making it a valuable tool for research in cancer biology and developmental studies.

Glaucocalyxin A is an ent-kauranoid diterpene derived from Rabdosia japonica var. This compound acts as an apoptosis inducer by inhibiting the nuclear translocation of Five-zinc finger Glis 1 (GLI1), effectively modulating the PI3K/Akt signaling pathway. Its notable antitumor properties make Glaucocalyxin A a valuable reagent for research in cancer biology, particularly in studies focused on osteosarcoma.

Ipatasertib tosylate is a potent and selective ATP-competitive inhibitor of pan-Akt, exhibiting IC50 values of 5, 18, and 8 nM for Akt1, Akt2, and Akt3, respectively. By inhibiting Akt, Ipatasertib tosylate activates FoxO3a and NF-κB, resulting in p53-independent activation of PUMA and subsequent apoptosis in cancer cells. This compound demonstrates significant anti-tumor activity in xenograft mouse models, making it a valuable tool for cancer research and therapeutic development.

MK-2206 free base is a highly potent and selective allosteric inhibitor of the Akt signaling pathway, exhibiting IC50 values of 8 nM, 12 nM, and 65 nM for Akt1, Akt2, and Akt3, respectively. This compound demonstrates significant anticancer properties, particularly against breast cancer cell lines, as well as those harboring PIK3CA mutations and PTEN loss. MK-2206 free base is valuable for research applications focused on cancer biology and therapeutic development targeting the Akt pathway.

Degalactotigonin is a saponin-selective inhibitor that targets key pathways, including EGFR, GSK3β, and Hedgehog/Gli1. It effectively inhibits EGFR phosphorylation and the downstream Akt/ERK signaling pathway, while also disrupting the Hedgehog/Gli1 pathway through the inactivation of GSK3β. These actions result in the induction of apoptosis in cancer cells, cell cycle arrest, and inhibition of cell migration and invasion. Degalactotigonin is suitable for research focused on malignant tumors, particularly pancreatic cancer and osteosarcoma.

MK-2206 is a highly potent and selective allosteric inhibitor of the Akt signaling pathway, exhibiting IC50 values of 8, 12, and 65 nM for Akt1, Akt2, and Akt3, respectively. This compound demonstrates significant anticancer activity, particularly in breast cancer cell lines and those harboring PIK3CA mutations or loss of PTEN function. MK-2206 is valuable for research investigating Akt's role in cancer progression and therapeutic resistance.

Adropin (34-76) is a secretory fragment of the Adropin protein known for its role as a hypoglycemic agent. This compound effectively reduces cAMP levels and inhibits glucose production in hepatocytes, contributing to its hypoglycemic effect. Additionally, Adropin (34-76) demonstrates antifibrotic properties through the inhibition of the GLI1 signaling pathway, making it valuable for research in metabolic regulation and fibrosis-related studies.

Hematein is an allosteric inhibitor of casein kinase II, exhibiting an IC50 of 0.74 μM. It demonstrates significant biological activity by inhibiting Akt/PKB Ser129 phosphorylation and the Wnt/TCF signaling pathway. Research applications include studying apoptosis in lung cancer cells, making it a valuable reagent for cancer biology investigations.

Chikusetsusaponin IVa methyl ester is a natural triterpenoid saponin that functions as a Wnt/β-catenin, NF-κB, and AP-1 inhibitor. It induces G0/G1 cell cycle arrest and apoptosis in colon cancer cells through the inhibition of the Wnt/β-catenin signaling pathway. Additionally, this compound significantly decreases the production of nitric oxide, prostaglandin E₂, and pro-inflammatory cytokines, while downregulating iNOS and COX-2 levels. Chikusetsusaponin IVa methyl ester is valuable for research focused on colorectal cancer and inflammatory processes.

HDAC/CK2-IN-1 is an inhibitor targeting histone deacetylases HDAC1 and HDAC6, with IC50 values of 1.46 μM and 0.66 μM, respectively, as well as casein kinase 2 (CK2) with an IC50 of 3.67 μM. This compound demonstrates significant antiproliferative effects on various cancer cell lines, including Jurkat, MCF-7, HCT-116, and HL-60. It serves as an important research tool for studying the roles of histone modifications and CK2 in tumor biology and could have potential implications in the development of cancer therapeutics.

IOR-160 is a dual inhibitor targeting casein kinase 2 (CK2) and histone deacetylases (HDACs). It showcases high selectivity for CK2, with an IC50 of 1.7 nM, and demonstrates broad inhibitory effects on HDACs 1, 2, 3, and 6, with IC50 values of 3.3 nM, 24.0 nM, 3.9 nM, and 13.0 nM, respectively. Through the inhibition of AKT phosphorylation and the enhancement of acetylated α-tubulin levels, IOR-160 effectively modulates critical cellular signaling pathways. This compound is particularly relevant in research focused on triple-negative breast cancer, where it has been shown to inhibit tumor growth and reduce tumor burden.

NL-103 is a potent histone deacetylase (HDAC) inhibitor, exhibiting IC50 values of 21.3 nM, 57 nM, 74 nM, and 680 nM for HDAC1, HDAC2, HDAC3, and HDAC6, respectively. This compound also targets the Hedgehog signaling pathway, leading to the downregulation of Gli2 expression. NL-103 is primarily utilized in cancer research, providing valuable insights into HDAC regulation and its role in tumor biology.

(S)-Trichostatin A is a selective inhibitor of HDAC6, demonstrating IC50 values of 9.88 nM and 11.1 nM for Zebrafish and Human HDAC6, respectively. It exhibits weak inhibition of other human HDACs, making it a valuable tool for studying HDAC6's role in cellular processes. This compound is useful in research applications related to cancer, neurodegenerative diseases, and epigenetic regulation.

Windorphen is a selective Wnt/β-catenin signaling inhibitor that specifically interferes with the c-terminal transactivation domain of β-catenin-1, while leaving β-catenin-2 unaffected. This compound targets p300, effectively disrupting the interaction between β-catenin and p300 without impacting CBP. Windorphen is valuable for research applications focused on β-catenin-related pathways, cancer biology, and developmental processes.

GSK-3β/G9a-IN-1 is a selective inhibitor of GSK-3β and G9a, acting through competitive mechanisms with IC50 values of 0.8 μM and 1.1 μM, respectively. This compound is effective in lowering tau phosphorylation and reducing Aβ aggregation, making it relevant for Alzheimer's disease research. Additionally, GSK-3β/G9a-IN-1 influences chromatin dynamics by inhibiting H3K9me2 and modulating members of the SAGA complex. Its ability to improve memory and restore social behaviors highlights its potential as a therapeutic agent in neurodegenerative conditions.

Pipecolic acid is a metabolite of lysine that acts as a YAP-GPX4 signaling modulator. It exhibits antioxidant properties and has been shown to reduce retinal vascular tube formation while mitigating ferroptosis. This compound enhances voltage-sensitive Ca2+ channel currents and can induce neuronal apoptosis, making it a valuable tool for research on diabetic retinopathy. Its ability to cross the blood-brain barrier further supports its application in neurological studies.

Prostaglandin E1 ethanolamide is a prostaglandin analog that primarily targets the GLI2 signaling pathway. This compound has been shown to inhibit GLI2-induced expression of downstream genes such as Gli1 and Ptch1, demonstrating its potential in regulating tumor growth. As a valuable tool for cancer research, Prostaglandin E1 ethanolamide may facilitate investigations into therapeutic strategies that disrupt GLI2-mediated oncogenic processes.

WEE1 Degrader 1 is a CRBN-dependent molecular glue degrader that targets WEE1 and casein kinase 1α (CK1α) with sub-2 nM DC50 values for both proteins. This compound effectively induces the proteasomal degradation of its targets, providing a valuable tool for studying cell cycle regulation. WEE1 Degrader 1 is particularly relevant in the research of acute lymphoblastic leukemia, acute monocytic leukemia, acute promyelocytic leukemia, colorectal adenocarcinoma, and diffuse large B-cell lymphoma.

MK-0752 inhibits the Notch signaling pathway, which may result in induction of growth arrest and apoptosis in tumor cells in which the Notch signaling pathway is overactivated.

TWS119 is a 4,6 disubstituted pyrrolopyrimidine that potently inhibits GSK3β with an IC50 value of 30 nM.1 At 400 nM.

GDC-0068 is a selective, ATP-competitive, pan-Akt inhibitor that targets Akt1, 2, and 3 with IC50 values of 5, 18, and 8 nM, respectively in cell-free assays

Begacestat is a novel, selective thiophene sulfonamide inhibitor of amyloid precursor protein gamma-secretase for the treatment of Alzheimer's disease.

PF-03084014 is a reversible and selective inhibitor of γ-secretase with IC50 value of 6.2 nM .

BMS 433796 is a γ-secretase inhibitor with Aβ lowering activity in a transgenic mouse model of Alzheimer's disease.

TAK-441 is a pyrrolo[3,2-c]pyridine derivative, as a highly potent and orally active hedgehog signaling inhibitor.

gamma-secretase modulator 1 is a gamma-secretase modulator, gamma-secretase modulator 1 is useful for Alzheimer's disease.

gamma-secretase modulator 2 is a potent and selective gamma-secretase modulator for treatment of Alzheimer's disease.

GANT 58 is a potent Gli antagonist that inhibits GLI1-induced transcription with IC50 of 5 μM.

Potent and selective casein kinase 1ε (CK1ε) and CK1δ inhibitor (IC50 values are 7.7 and 14 nM respectively) that displays > 30-fold selectivity over 42 other common kinases. Inhibits PER protein nuclear translocation (EC50 = 290 nM) causing phase shifts in circadian rhythms and attenuates methamphetamine-stimulated locomotion in vivo.

Prostaglandin E2 is a hormone-like substance that participate in a wide range of body functions such as the contraction and relaxation of smooth muscle, the dilation and constriction of blood vessels, control of blood pressure, and modulation of inflammation.

TDZD-8 protects the brain against I/R injury by inhibiting GSK-3beta activity

LY3039478 is a orally bioavailable, novel small molecule Notch inhibitor with an IC50 of ~1nM in most of the tumor cell lines tested.

LH 846 is a selective inhibitor of casein kinase (CK) 1δ (IC50 values are 290 nM, 1.3 μM and 2.5 μM for CK1δ, ε and α)

A-3 Hydrochloride is an inhibitor of PKA (cAMP-dependent protein kinase, Ki=4.3μM) and cGMP-dependent protein kinase, Ki=3.8μM, PKC (protein kinase C, Ki=47μM), casein kinase I and II, and MLCK (myosin light chain kinase) ( Ki=7.4μM).