Tyk2-IN-9 is a potent,selective and specific inhibitor of JAK kinases, inhibits Tyk2, JAK1 and JAK2 with IC50 values of 6 nM, 21nM and 6nM, respectively. Tyk2-IN-9, example 19, is extracted from patent US2017240552A1[1].
IMR-1 is a novel class of Notch inhibitors targeting the transcriptional activation with IC50 of 6 μmol/L.target: NotchIC 50: 6 μmol/LIn vitro: IMR-1 prevents the recruitment of Maml1 to the NTC on chromatin, inhibits Notch target gene transcription, and dramatically inhibits tumor growth .A decrease in colony formation of Notch-dependent cell lines is observed upon treatment with IMR-1 when compared with the control (DMSO). In vivo : The reference for intraperitoneal injection is 15 mg/kg. IMR-1 inhibits Notch-dependent somite development in zebrafish.
Thiazovivin is a potent ROCK inhibitor, which can protect human embryonic stem cells.
Cryptotanshinone is a natural compound extracted from the root of Salvia miltiorrhiza Bunge that shows antitumor activities. Cryptotanshinone inhibits STAT3 with an IC50 of 4.6 μM.
(E)-Osmundacetone is the isomer of Osmundacetone. Osmundacetone significantly suppresses the phosphorylation of MAPKs, including JNK, ERK, and p38 kinases. Osmundacetone has a neuroprotective effect against oxidative stress[1].
L-685458 is a potent inhibitor of Amyloid β-Protein precursor γ-secretase activity with IC50 of 17 nM, shows greater than 50-100-fold selectivity over other aspartyl proteases tested.IC50 value: 17 nMTarget: γ-secretasein vitro: L-685458 is a Notch inhibitor. L-685458 blocks Notch activation in the two cell lines in terms of reduced cytoplasmic distribution and almost diminished nuclear labelling of Hes1 proteins. [2] L-685458 is a γ-secretase inhibitor. [3]
GDC-046 is a potent, selective, and orally bioavailable TYK2 inhibitor with Kis of 4.8, 0.7, 0.7, and 0.4 nM for TYK2, JAK1, JAK2, and JAK3, respectively[1].
CK2-IN-7 (compound 2) is an inhibitor of casein kinase 2 (CK2). CK2-IN-7 shows synergistic effect with structurally distinct CK2 chemical probe: SGC-CK2-1, against cancer[1].
ICG-001 is an inhibitor of β-catenin/TCF mediated transcription. It works by specifically binding to cyclic AMP response element-binding protein with an IC50 of 3 μM.
FzM1.8 derives from FzM1, is an allosteric agonist of FZD4 with pEC50 of 6.4. FzM1.8 binds to FZD4 and activates the WNT/β-catenin pathway, by promoting TCF/LEF transcriptional activity in the absence of any WNT ligand. FzM1.8 binding stabilizes FZD4 with an increased affinity for heterotrimeric G protein and stimulates the release of the Gβγ subunit that in turn activates PI3K[1].
IC261 is a selective, ATP-competitive CK1 inhibitor, with IC50s of 1 μM, 1 μM, 16 μM for Ckiδ, Ckiε and Ckiα1, respectively.
Urolithin B is one of the gut microbial metabolites of ellagitannins, and has anti-inflammatory and antioxidant effects. Urolithin B inhibits NF-κB activity by reducing the phosphorylation and degradation of IκBα, and suppresses the phosphorylation of JNK, ERK, and Akt, and enhances the phosphorylation of AMPK. Urolithin B is also a regulator of skeletal muscle mass[1][2].
Rhodblock 6 is a Rho kinase (ROCK) inhibitor that inhibits phospho-MRLC (myosin regulatory light chain) localization[1].
CAY10746 is a selective Rho kinase (ROCK) inhibitor. CAY10746 has inhibitory activity for ROCK I, ROCK II with IC50 values of 0.014 μM and 0.003 μM, respectively. CAY10746 can be used for the research of diabetic retinopathy (DR)[1].
PF-5006739 is a potent and selective inhibitor of CK1δ/ε with IC50s of 3.9 nM and 17.0 nM, respectively. PF-5006739 is a potential therapeutic agent for a range of psychiatric disorders with low nanomolar in vitro potency for CK1δ/ε and high kinome selectivity. PF-5006739 attenuats opioid drug-seeking behavior in a rodent operant reinstatement model in animals in a dose-dependent manner[1]. PF-5006739 improves glucose tolerance in both diet-induced obesity (DIO) and genetic (ob/ob) mice models of obesity[2].
SMO-IN-1 (Compound 15) is an orally active Smoothened (SMO) inhibitor with an EC50 of 89 nM against sonic Hh protein (shh)[1].
EHT 5372 is a strong inhibitor of DYRK’s family kinases, with IC50s of 0.22, 0.28 nM for DYRK1A and DYRK1B, respectively.
MRT-10 is a seven-transmembrane receptor smoothened (Smo) antagonist with an IC50 of 0.65 μM in the micromolar range in various Hedgehog (Hh) assays. MRT-10 binds to the Smo receptor at the level of the Bodipycyclopamine binding site. MRT-10 can be used for the research of cancer[1][2].
GSK-3 inhibitor 4 is an orally active and brain-penetrant inhibitor of GSK-3, CDK2, and CDK5, with IC50 values of 0.56 nM (GSK-3β), 0.45 nM (GSK-3α), 0.47 μM, and 0.68 μM, respectively. GSK-3 inhibitor 4 effectively reduces the phosphorylation level of Tau protein. GSK-3 inhibitor 4 can be used in Alzheimer's disease (AD) studies[1].
Bohemine is a purine analogue and is a synthetic and selective CDK inhibitor with IC50s of 4.6 μM, 83 μM, and 2.7 μM for Cdk2/cyclin E, Cdk2/cyclin A, and Cdk9/cyclin T1, respectively. Bohemine also inhibits ERK2 with an IC50 of 52 μM and has less inhibitory effect on CDK1, CDK4 and CDK6. Bohemine has a broad spectrum anti-cancer activities[1][2].
ERK5-IN-4 (compound 34b) is a potent and selective inhibitor of extracellular signal-related kinase 5 (ERK5). ERK5-IN-4 inhibits ERK5 (full-length) and truncated ERK5 (ERK5 ΔTAD) kinase activity in HEK293 cells with an IC50 of 77 nM and 300 nM, respectively[1].
Kenpaullone is a potent inhibitor of CDK1/cyclin B and GSK-3β, with IC50s of 0.4 μM and 23 nM, and also inhibits CDK2/cyclin A, CDK2/cyclin E, and CDK5/p25 with IC50s of 0.68 μM, 7.5 μM, 0.85 μM, respectively.
BMS-833923 (XL-139) is an orally bioavailable small-molecule inhibitor of Smoothened with potential antineoplastic activity; inhibits BODIPY cyclopamine binding to SMO in a dose-dependent manner with an IC50 of 21 nM.IC50 Value: 6-35 nM [1]Target: SmoothenedSMO antagonist BMS-833923 inhibits the sonic hedgehog (SHH) pathway protein SMO, which may result in a suppression of the SHH signaling pathway.in vitro: In vitro, BMS-833923 inhibits the expression of downstream effectors in the HH pathway (GLI1 and PTCH1) in cell lines that express wild-type SMO and those which express activated mutant forms of SMO (IC50values of 6-35 nM). In FACS-based binding assays, BMS-833923 inhibits BODIPY cyclopamine binding to SMO in a dose-dependent manner with an IC50 of 21 nM [1]. in vivo: Pharmacodynamic studies show that BMS-833923 robustly inhibits HH pathway activity with along duration of action after a single oral dose in medulloblastoma and pancreatic carcinoma xenograft models. The pharmacodynamic effects of BMS-833923 observed in these models translate into tumor growth inhibition at well-tolerated doses [1].Clinical trial: Dasatinib Combo With Smoothened (SMO) Antagonist (BMS-833923). Phase 2
CMPD101, is a novel membrane-permeable, small-molecule inhibitor of both GRK2 and GRK3 with IC50s of 18 nM and 5.4 nM. CMPD101 also inhibits ROCK-2 and PKCα (IC50s=1.4 μM and 8.1 μM, respectively)[1].
Ascochlorin (Ilicicolin D), an isoprenoid antibiotic, mediates its anti-tumor effects predominantly through the suppression of STAT3 signaling cascade. Ascochlorin induces apoptosis. Anti-inflammatory activity[1][2][3].
POP-3MB (compound 1b) is an ICMT inhibitor (IC50: 2.5 μM). POP-3MB changes the subcellular localization of K-Ras and inhibits Ras activation. POP-3MB also inhibits Erk phosphorylation[1].
YAP-TEAD-IN-1 TFA is a potent and competitive peptide inhibitor of YAP-TEAD interaction (IC50=25 nM). YAP-TEAD-IN-1 TFA is a 17mer peptide and shows a higher the binding affinity to TEAD1 (Kd=15 nM) than YAP (50-171) (Kd= 40 nM)[1].
Windorphen is a Wnt/β-catenin signal inhibitor that specifically targets the function of the c-terminal transactivation domain of β-catenin-1 but not β-catenin-2. Windorphen selectively targets p300, disrupting the association of the mammalian β-catenin with p300 but not CBP[1].
Thi-DPPY (compound 8e) is a potent and orally active JAK3 inhibitor with IC50 values of 62.4, 1.38 nM for BTK, JAK, respectively. Thi-DPPY shows anti-proliferative activity against HBE cells. Thi-DPPY shows anti-inflammatory activity in vivo. Thi-DPPY has the potential for the research of idiopathic pulmonary fibrosis (IPF)[1].
Fz7-21S is a negative control of Fz7-21. Fz7-21 is a potent peptide antagonist of FZD7 receptors[1].