GSK-3β inhibitor 10 (compound 14a) is a highly potent GSK-3β inhibitor with an IC50 value of 80.5 nM. GSK-3β inhibitor 10 can be used for researching Alzheimer’s disease[1].
KY-05009 is an ATP-competitive Traf2- and Nck-interacting kinase (TNIK) inhibitor with a Ki of 100 nM. KY-05009 pharmacologically inhibits TGF-β1-induced epithelial-to-mesenchymal transition (EMT) in human lung adenocarcinoma cells. KY-05009 inhibits the protein expression of TNIK and transcriptional activity of Wnt target genes and induces apoptosis in cancer cells. KY-05009 exerts anti-cancer activity[1].
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.
Laxiflorin B, a herbal compound, is a novel selective ERK1/2 inhibitor that has antitumor activity[1].
F7H is a Frizzled receptor FZD7 antagonist (IC50: 1.25 μM). Frizzled receptors (FZDs) influence Wnt signaling, mediating embryonic development and tissue homeostasis. F7H is a potent ligand for the FZD7 transmembrane domain (TMD)[1].
BMS-906024 is an oral and selective gamma secretase inhibitor (GSI) that is a small molecule Notch inhibitor[1]. BMS-906024 prevents the activation of all four Notch receptors with a high oral bioavailability with IC50s of 1.6, 0.7, 3.4, and 2.9 nM for Notch1, -2, -3, and -4 receptors, respectively. BMS-906024 demonstrates broad-spectrum antineoplastic activity against a wide array of human cancer xenografts[2].
Prodigiosin (Prodigiosine) hydrochloride is a red pigment produced by bacteria as a bioactive secondary metabolite. Prodigiosin hydrochloride is a potent proapoptotic agent, and inhibits Wnt/β-catenin pathway. Prodigiosin hydrochloride has antibacterial, antifungal, antiprotozoal, antimalarial, immunosuppressive, and anticancer properties[1][2].
DK419 is a potent and orally active Wnt/β-catenin signaling inhibitor, with an IC50 of 0.19 μM. DK419 reduces protein lelvels of Axin2, β-catenin, c-Myc, Cyclin D1 and Survivin and induces production of pAMPK[1].
Casein kinase 1δ-IN-9 (compound 737) is a potent casein kinase 1δ (CK1δ/CK15) inhibitor. Casein kinase 1δ-IN-9 can be used for the research of neurodegenerative disorders such as Alzheimer's disease[1].
ROCK-IN-1 is a potent inhibitor of ROCK, with an IC50 of 1.2 nM for ROCK2.
JAK-IN-21 (Example 4) is a selective and potent JAK inhibitor with IC50s of 1.73, 2.04, 109 and 62.9 nM against JAK1, JAK2, J2V617F and TYK2, respectively[1].
AChE/GSK-3β-IN-1 (compound GT15) is a potent, dual AChE/GSK-3β inhibitor with IC50 values of 1.2, 149.8 and 22.4 nM for hAChE , hBChE and hGSK-3β, respectively. AChE/GSK-3β-IN-1 penetrates the blood-brain barrier (BBB). AChE/GSK-3β-IN-1 has high kinase selectivity profiles for the CMGC kinase family. AChE/GSK-3β-IN-1 occupies the ATP binding site of DYRK1A. AChE/GSK-3β-IN-1 inhibits ROS expression and reduces oxidative stress. AChE/GSK-3β-IN-1 can be used for Alzheimer’s disease research[1].
Cearoin, isolated from Dalbergia odorifera, increases autophagy and apoptosis through the production of ROS and the activation of ERK[1].
EVT801 is an orally active and selective inhibitor of VEGFR-3 (IC50=11 nM), which has antitumor effects. EVT801 inhibits not only VEGF-C-induced human endothelial cell proliferation, but also tumor (lymphatic) angiogenesis in tumor mouse models. EVT801 can reduce tumor hypoxia, immunosuppressive cytokines (CCL4, CCL5) and myeloid derived suppressor cells (MDSC) production. EVT801 has synergistic effect with immune checkpoint therapy (ICT), which improves ICT response rate and has better inhibitory effect on cancer mouse models[1].
LY294002 hydrochloride is a potent and broad-spectrum PI3K inhibitor, with IC50 values of 0.5, 0.57, and 0.97 μM for P110α, P110δ and P110β, respectively. LY294002 hydrochloride also inhibits CK2 with an IC50 of 98 nM. LY294002 hydrochloride can be used for pancreatic cancer research[1][2][3].
KY1220 is a compound that destabilizes both β-catenin and Ras, via targeting the Wnt/β-catenin pathway; with an IC50 of 2.1 μM in HEK293 reporter cells.
EMT inhibitor-1 is an inhibitor of of Hippo, TGF-β, and Wnt signaling pathways with antitumor activities.
Dehydrocrenatidine, a natural alkaloid, is a specific JAK inhibitor. Dehydrocrenatidine inhibits voltage-gated sodium channels and ameliorates mechanic allodia in a rat model of neuropathic pain[1][2].
Upadacitinib (ABT-494) tartrate tetrahydrate is a potent, orally active and selective Janus kinase 1 (JAK1) inhibitor (IC50=43 nM). Upadacitinib tartrate tetrahydrate displays approximately 74 fold selective for JAK1 over JAK2 (200 nM) in cellular assays dependent on specific, relevant cytokines. Upadacitinib tartrate tetrahydrate can be used for several autoimmune disorders research[1][2].
Valproic acid (VPA) sodium (2:1) is an orally active HDAC inhibitor, with IC50 in the range of 0.5 and 2 mM, also inhibits HDAC1 (IC50, 400 μM), and induces proteasomal degradation of HDAC2. Valproic acid sodium (2:1) activates Notch1 signaling and inhibits proliferation in small cell lung cancer (SCLC) cells. Valproic acid sodium (2:1) is used in the treatment of epilepsy, bipolar disorder, metabolic disease, HIV infection and prevention of migraine headaches[1][2][3][4][5][6][7].
Eupalinolide K, a sesquiterpene lactones compound from Eupatorium lindleyanum, is a STAT3 inhibitor. Eupalinolide K is a Michael reaction acceptor (MRA) [1].
Taladegib (LY2940680) is an antagonist of the smoothened receptor.
JAK-2/3-IN-2 (Compound 3h) is a JAK2 and JAK3 inhibitor with IC50s of 23.85 nM and 18.9 nM, respectively[1].
JAK-IN-18 is a potent inhibitor of JAK. JAK-IN-18 is useful for the research of multiple diseases, particularly ocular, skin, and respiratory diseases (extracted from patent WO2018204238A1, compound 1)[1].
Pamoic acid disodium is a potent GPR35 agonist with an EC50 value of 79 nM. Pamoic acid disodium induces GPR35 internalization and activates ERK1/2 with EC50 values of 22 nM and 65 nM, respectively. Pamoic acid disodium potently recruits β-arrestin2 to GPR35 and has an antinociceptive effect[1].
HTH-01-091 is a potent and selective, cell-permeable, ATP-competitive MELK inhibitor with biochemical IC50 of 10.5 nM; displays no significant activity for PIK3CA, mTOR, GSK3A and CDK7 (IC50>600 nM); exhibits substantially improved kinome selectivity in comparison with OTSSP167; induces MELK degradation, but demonstrates poor antiproliferative effects in basal-like breast cancer cell lines.
SJ988497 is a PROTAC JAK2 degrader. SJ988497 potently inhibits CRLF2-rearranged (CRLF2r) cell proliferation and degrades the CRBN neosubstrate GSPT1. SJ988497 consists of a Ruxolitinib (HY-50856) derivative, linker, and CRBN ligand Pomalidomide. SJ988497 can be used in the research of acute lymphoblastic leukemia (ALL)[1].
H-Ile-Lys-Val-Ala-Val-OH is one of the most potent active sites of laminin-1. H-Ile-Lys-Val-Ala-Val-OH promotes cell adhesion, neurite outgrowth, and tumor growth. H-Ile-Lys-Val-Ala-Val-OH stimulates BMMSC population growth and proliferation by activating MAPK/ERK1/2 and PI3K/Akt signalling pathways[1][2].
TA-01 is a potent CK1 and p38 MAPK inhibitor, with IC50s of 6.4 nM, 6.8 nM, 6.7 nM for CK1ε, CK1δ and p38 MAPK, respectively.
IWP-2 is an inhibitor of Wnt processing and secretion with IC50 of 27 nM.