SSTC3 is a novel small-molecule CK1α activator with EC50 of 30 nM (WNT-driven reporter gene assay), Kd of 32 nM; has better pharmacokinetic properties than pyrvinium, attenuates the growth of such Apc mutant organoids with EC50 of 2.9 uM; decreases the viability of the WNT-dependent cell lines (EC50 = 132, 63, and 123 nM for HT29, SW403, and HCT116 cells, respectively), inhibits the growth of CRC xenografts in mice; also attenuates the growth of patient-derived metastatic CRC xenograft, with minimal gastrointestinal toxicity compared to other classes of WNT inhibitors.
3-epi-Vitamin D3 (Epicholecalciferol) (Compound 4), a Vitamin D3 analogue, is a Hedgehog pathway inhibitor with an IC50 of 39.2 μM measured in U87MG cells[1].
Ulixertinib (VRT752271) is a reversible, ATP-competitive inhibitor of ERK1 and ERK2 kinases, with IC50 of <0.3 nM against ERK2.
BRD0705 (BRD-0705) is a potent, paralog-selective GSK3α inhibitor with IC50 of 66 nM, 8-fold selectivity over GSK3β (IC50=515 nM); displays excellent selectivity in a penal of 311 kinases, the CDK family of CDK2, CDK3 and CDK5) are most potently inhibited with IC50 of 6.87, 9.74 and 9.20 uM (87-, 123-, and 116-fold selectivity relative to GSK3α); inhibits GSK3α kinase function, impairs GSK3α Tyr279 phosphorylation in a time- and concentration-dependent manner without affecting GSK3β Tyr216 phosphorylation, and does not stabilize β-catenin, induces myeloid differentiation and impairs colony formation in AML cells, with no apparent effect on normal hematopoietic cells; impairs leukemia initiation and prolongs survival in AML mouse models.
CHPG sodium salt is a selective mGluR5 agonist, and attenuates SO2-induced oxidative stress and inflammation through TSG-6/NF-κB pathway in BV2 microglial cells[1]. CHPG sodium salt protects against traumatic brain injury (TBI) in vitro and in vivo by activation of the ERK and Akt signaling pathways.[2].
OAC1 is a Octamer-binding transcription factor 4 (Oct4)-activating compound; enhances the iPSC reprogramming efficiency and accelerated the reprogramming process.IC50 value: Target: Oct4 activatorin vitro: OAC1 enhances the formation of Oct4-GFP+ colonies and accelerates the dynamics of reprogramming. OAC1 enhanced reprogramming efficiency through a mechanism that is independent of endogenous Oct4 promoter demethylation. OAC1 enhanced reprogramming efficiency through a mechanism that is distinct from suppressing p53-p21 expression. Luciferase assay revealed that OAC1 had no effect on Topflash activity, although BIO activated the Topflash reporter potently. OAC1 functions through a mechanism that is independent of the Wnt signaling.
Peficitinib (ASP015K) hydrobromide is an orally active JAK inhibitor, with IC50s of 3.9, 5.0, 0.7 and 4.8 nM for JAK1, JAK2, JAK3 and Tyk2, respectively.
trans-Zeatin-d5 is deuterium labeled trans-Zeatin. trans-Zeatin is a plant cytokinin, which plays an important role in cell growth, differentiation, and division; trans-Zeatin also inhibits UV-induced MEK/ERK activation.
JAK-STAT-IN-1 (compound 1) is a selective JAK-STAT inhibitor. JAK-STAT-IN-1 can be used for the research of autoimmune disorder[1].
ERK-IN-4 is an ERK inhibitor binds preferentially to ERK2 with a Kd of 5 μM. ERK-IN-4 specificity inhibits ERK Rsk-1 and Elk-1 phosphorylation. ERK-IN-4 has little effect on ERK protein phosphorylation by its upstream activator MEK1/2[1].
HDAC/JAK/BRD4-IN-1(compound 25ap) is a potent HDAC/JAK/BRD4 triple inhibitor. HDAC/JAK/BRD4-IN-1 inhibit cell growth and induces apoptosis in MDA-MB-231 cells, and shows anticancer activity in vivo[1].
Mongersen is a 21-mer phosphorothioate antisense oligonucleotide targeting the mRNA of the Smad7 protein, thus leading to suppression of TGF-β1 pathways and remission of Crohn's disease.
JAK3/BTK-IN-2 is a potent inhibitor of JAK3/BTK. BTK and JAK3 are two important targets for autoimmune diseases. Simultaneous inhibition of the BTK/JAK3 signalling pathway exhibits synergistic effects. JAK3/BTK-IN-2 has the potential for the research of JAK3 kinase and/or BTK-related diseases (extracted from patent WO2021147952A1, compound 004)[1]
Ripasudil (K-115) is a specific inhibitor of ROCK, with IC50s of 19 and 51 nM for ROCK2 and ROCK1, respectively.
GSK-3 inhibitor 3 is a selective, orally active and brain-penetrant inhibitor of GSK-3, with IC50s of 0.35 nM and 0.25 nM for GSK-3α and GSK-3β, respectively. GSK-3 inhibitor 3 lowers levels of tau protein phosphorylation at S396 in a triple-transgenic mouse Alzheimer’s disease model, with IC50 of 10 nM. GSK-3 inhibitor 3 can be used for neurological disease research[1].
MK-4101 is a potent SMO Inhibitor of the Hedgehog Pathway, highly active against Medulloblastoma and Basal Cell Carcinoma.target:SMOIn vivo: MK-4101 was highly efficacious against primary medulloblastoma and BCC developing in the cerebellum and skin of Ptch1+/- mice.In vitro: MK-4101 induce deregulation of cell cycle and block of DNA replication in tumors. MK-4101 targets the Hh pathway in tumor cells, showing the maximum inhibitory effect on Gli1. MK-4101 also induce deregulation of cell cycle and block of DNA replication in tumors.
MAPK-IN-1 (Compound 2) is a MAPK signaling pathway inhibitor. MAPK-IN-1 exhibits AChE inhibitory activity with an IC50 of 23.84 μM. MAPK-IN-1 shows anti-neuroinflammatory and neuroprotective activity and can be used for Alzheimer's disease research[1].
Tyk2-IN-5 (compound 6) is a highly potent, selective and orally active Tyk2 inhibitor and targets the JH2 domain, with a Ki of 0.086 nM for Tyk2 JH2 and an IC50 of 25 nM for IFNα. Highly effective in inhibiting IFNγ production in a rat pharmacodynamics model and fully efficacious in a rat adjuvant arthritis model[1].
GS87 is a highly specific and potent GSK3 inhibitor with IC50s of 415nM and 521nM for GSK3α and GSK3β, respectively. GS87 induces differentiation of acute myeloid leukemia (AML) cell lines by effectively activating GSK3-dependent signaling components including MAPK signaling. GS87 modulates key GSK3 target proteins involved in cell proliferation and differentiation more effectively than Lithium and SB415285 (SB). GS87 has the potential for acting as a differentiation agent for non-promyelocytic AML research[1].
S-Propargylcysteine (SPRC), a structural analog of S-allyl cysteine (SAC), is a slow H2S-releasing compound. S-Propargylcysteine reduces Ca2+ accumulation and inflammatory cytokines, inhibits STAT3, and elevates p53 and Bax. S-Propargylcysteine has anti-inflammatory activity and protects mice against acute pancreatitis. S-Propargylcysteine also has cardioprotective, neuroprotective acitivties[1][2].
Cirevetmab (ZTS-00521426) is an immunoglobulin G2-kappa, anti-[Canis lupus familiaris TGFB1], caninized monoclonal antibody. Cirevetmab is an immunomodulator[1].
NMDAR/TRPM4-IN-2 (compound 8) is a potent NMDAR/TRPM4 interaction interface inhibitor. NMDAR/TRPM4-IN-2 shows neuroprotective activity. NMDAR/TRPM4-IN-2 prevents NMDA-induced cell death and mitochondrial dysfunction in hippocampal neurons, with an IC50 of 2.1 μM. NMDAR/TRPM4-IN-2 protects mice from MCAO-induced brain damage and NMDA-induced retinal ganglion cell loss[1].
IQA (CGP-029482) is a potent and selective protein kinase CK2 inhibitor[1].
Pamidronic acid is a drug used to treat a broad spectrum of bone absorption diseases.
SWTX-143 is a novel covalent YAP/TAZ-TEAD inhibitor that binds to the palmitoylation pocket of all four TEAD isoforms. SWTX-143 causes irreversible and specific inhibition of the transcriptional activity of YAP/TAZ-TEAD and shows antitumor activity[1].
AZ-3 is a potent and selective JAK1 inhibitor with an IC50 of 34 nM.
Zotiraciclib (TG02) is an orally active potent inhibitor of CDK2, JAK2 and FLT3 with IC50 values of 13, 73, and 56 nM, respectively. Zotiraciclib can be used for the research of advanced leukemias and multiple myeloma[1][2].
Ifidancitinib is a potent and selective inhibitor of JAK kinases 1/3. Ifidancitinib can be used in studies of allergies, asthma and autoimmune diseases[1].
CK2/PIM1-IN-1 is an inhibitor of CK2 and PIM1, with IC50s of 3.787 μM and 4.327 μM for CK2 and PIM1, respectively. CK2/PIM1-IN-1 is developed for the research of proliferative disorders such as cancer, as well as other kinase-associated conditions including inflammation, pain, vascular disorders, pathogenic infections and certain immunological disorders[1].
Theaflavin 3,3'-digallate (TF3), the typical pigment in black tea, is a good antitumor agent. Theaflavin 3,3'-digallate is generally regarded as the effective component for the inhibitory effects against carcinogenesis without adverse side effects by affecting multiple signal transduction pathways, such as upregulating p53 and p21, inhibiting phosphorylation of the cell survival protein Akt and MAPK pathway, downregulation of NF-κB, shifting the ratio between pro-/antiapoptotic proteins. Theaflavin 3,3'-digallate causes a rapid and sustained decrease in phospho-ERK1/2 and -MEK1/2 protein expression. Theaflavin 3,3'-digallate inhibits HCT116 cell growth with an IC50 of 17.26 μM[1].