Xanthocillin is a marine agent extracted from Penicillium commune, induces autophagy through inhibition of the MEK/ERK pathway[1].
Casein kinase 1δ-IN-8 (compound 494) is an inhibitor of Casein kinase 1δ, Casein kinase 1δ-IN-8 can be used in the treatment of neurodegenerative disorders such as Alzheimer's disease[1].
STAT6-IN-3 (Compound 18a) is a STAT6 inhibitor (IC50= 44 nM). STAT6-IN-3 targets the Src Homology 2 (SH2) domain of STAT6. STAT6-IN-3 can be used for research of inflammation such as asthma[1].
(S)-BAY 2965501 is the left-handed isomer of BAY 2965501 (HY-153343). BAY 2965501 is a potent and selective diacylglycerol kinase zeta (DGKζ) inhibitor. BAY 2965501 induces pERK activation. BAY 2965501 can be used for the research of cancer[1].
HA-1004 is a selective inhibitor of PKA, which can inhibit lipolysis and induce vascular relaxation. HA-1004 is also a dual inhibitor of cyclic GMP-dependent protein kinase and cyclic AMP-dependent protein, and is involved in smooth muscle, second messenger, cyclic AMP and cyclic GMP regulation mechanisms. HA-1004 can be used as a vasodilator to inhibit the contraction of rabbit aortic strips, or to antagonize ERK and tyrosine hydroxylase (TH) phosphorylation in morphine abstinence rat models[1][2][3].
Minecoside is a CXCR4/STAT3 inhibitor with anticancer and anti-inflammatory activity. Minecoside decreases CXCR4 expression and suppresses STAT3 activation, thus to inhibit CXCL 12-induced invasion. Minecoside potently inhibits cancer metastasis and promotes apoptotic progression[1][2].
SD-1029 (NSC 371488) is a potent inhibitor of Stat3 activation, suppresses EGFP-Stat3 nuclear translocation at 10 uM in both BHK-21 and U2-OS cells; inhibits Stat3-mediated antiapoptotic protein expression (Bcl-XL, MCL-1, and survivin), and suppresses phosphotyrosine levels of JAK2; inhibits IL-6 or oncostatin-induced Stat3 nuclear translocation at micromolar range, enhances apoptosis induced by paclitaxel in human cancer cells.
GSK-3β inhibitor 11 (compound 21) is a glycogen synthase kinase-3β (GSK-3β) inhibitor (IC50=10.02 μM). GSK-3β inhibitor 11 can be used in neurodegenerative disease research[1].
Asiaticoside, a trisaccaride triterpene from Centella asiatica, suppresses TGF-β/Smad signaling through inducing Smad7 and inhibiting TGF-βRI and TGF-βRII in keloid fibroblasts; Asiaticoside shows antioxidant, anti-inflammatory, and anti-ulcer properties.
ACT001 is an orally active PAI-1 inhibitor by inhibiting the phosphorylation of PI3K and AKT. ACT001 inhibits the phosphorylation of STAT3 and PD-L1 expression by directly binding to STAT3. ACT001, a fumarate salt form of DMAMCL (a prodrug of Micheliolide), can cross the blood-brain barrier. ACT001 has potent anti-glioblastoma (GBM) activity and immunomodulatory effects[1][2].
Hu7691 is an orally active, selective Akt inhibitor with IC50s of 4.0 nM, 97.5 nM, 28 nM for Akt1, Akt2 and Akt3, respectively. Hu7691 inhibits tumor growth and enables decrease of cutaneous toxicity in mice[1].
KT5720 is a cell-permeable, potent, specific, reversible, ATP-competitive inhibitor of protein kinase A (PKA), with a Ki of 60 nM[1][2].
ETC-159 is a potent, orally available PORCN inhibitor. It inhibits β-catenin reporter activity with an IC50 of 2.9 nM.
Hydrochlorothiazide is a diuretic drug of the thiazide class. Target: OthersHydrochlorothiazide belongs to thiazide class of diuretics. It reduces blood volume by acting on the kidneys to reduce sodium (Na) reabsorption in the distal convoluted tubule. The major site of action in the nephron appears on an electroneutral Na+-Cl? co-transporter by competing for the chloride site on the transporter. By impairing Na transport in the distal convoluted tubule, hydrochlorothiazide induces a natriuresis and concomitant water loss. Thiazides increase the reabsorption of calcium in this segment in a manner unrelated to sodium transport. Additionally, by other mechanisms, Hydrochlorothiazide is believed to lower peripheral vascular resistance [1].
JAK3/BTK-IN-5 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-5 has the potential for the research of JAK3 kinase and/or BTK-related diseases (extracted from patent WO2021147953A1, compound 35)[1]
AC-4-130 is a novel, potent STAT5 SH2 domain inhibitor, binds to and efficiently blocks STAT5 activation and subsequent transcriptional activity, shows high selectivity for STAT5 over STAT1 and STAT3; disrupts STAT5 activation, dimerization, nuclear translocation, and STAT5-dependent gene transcription; substantially impairs the proliferation and clonogenic growth of human AML cell lines and primary FLT3-ITD+ AML patient cells in vitro and in vivo; synergistically increases the cytotoxicity of the JAK1/2 inhibitor Ruxolitinib and the p300/pCAF inhibitor Garcinol in vivo.
SR-1277 is a potent, selective and ATP competitive CK1δ/ε inhibitor, with IC50s of 49 nM and 260 nM, respectively. SR-1277 also inhibits FLT3, CDK4/cyclin D1, CDK6/cyclin D3 and CDK9/cyclin K, with IC50s of 305 nM, 1340 nM, 311 nM and 109 nM, respectively. SR-1277 can be used for the research of cancer[1].
Triptonide(NSC 165677; PG 492), extracted from Tripterygium wilfordii Hook, inhibited the proliferation of mouse splenocytes induced by suboptimal concentration of concanavalin A or lipopolysaccharide at concentrations of 0.02, 0.1, and 0.5 mg/ml.
ALK5-IN-34 is an selective orally active activin receptor-like kinase (ALK) inhibitor. ALK5-IN-34 can inhibit the activity of ALK5-IN-34 with an IC50 value of ≤10 nM. ALK5-IN-34 also has inhibitory of tumor growth and can be used for the research of proliferative diseases, such as cancer[1].
Indirubin-3'-monoxime is a potent GSK-3β inhibitor, and weakly inhibits 5-Lipoxygenase, with IC50s of 22 nM and 7.8-10 µM, respectively; Indirubin-3'-monoxime also shows inhibitory activities against CDK5/p25 and CDK1/cyclin B, with IC50s of 100 and 180 nM.
25-Deacetylcucurbitacin A is a Cucurbitane-Type triterpenoid and has the potential to be an anti-cancer agent and JAK/STAT3 signaling pathway inhibitor[1].
Z-Ile-Leu-aldehyde(Z-IL-CHO; GSI-XII) is a potent gamma-Secretase inhibitor; Notch signaling inhibitor.IC50 value:Target: gamma-Secretase inhibitorin vitro: GSI-XII induces apoptosis of murine MOPC315.BM myeloma cells with high Notch activity. GSI XII impairs murine osteoclast differentiation of receptor activator of NF-κB ligand (RANKL)-stimulated RAW264.7 cells in vitro [1]. Notch-signaling inhibition in HRS cells by the γ-secretase inhibitor (GSI) XII results in decreased alternative p52/RelB NF-κB signaling, interfering with processing of the NF-κB2 gene product p100 into its active form p52 [2]. GSI treatment induced morphologic erythroid differentiation and promoted hemoglobin production. GSI treatment suppressed short-term growth and colony formation, while treatment with GSI-XXI promoted the growth of AA cells [3].in vivo: In the murine MOPC315.BM myeloma model GSI XII has potent anti-MM activity and reduces osteolytic lesions as evidenced by diminished myeloma-specific monoclonal immunoglobulin (Ig)-A serum levels and quantitative assessment of bone structure changes via high-resolution microcomputed tomography scans [1].
Verteporfin is a photosensitizer for photodynamic therapy to eliminate the abnormal blood vessels in the eye associated with conditions such as age-related macular degeneration. Verteporfin is a YAP inhibitor which disrupts YAP-TEAD interactions.
Cirsilineol, a natural flavone compound, selectively inhibits IFN-γ/STAT1/T-bet signaling in intestinal CD4+ T cells. Cirsilineol has potent immunosuppressive and anti-tumor properties. Cirsilineol significantly ameliorates trinitro-benzene sulfonic acid (TNBS)-induced T-cell-mediated experimental colitis in mice[1].
VT103, an analog of VT101, is an orally active and selective TEAD1 protein palmitoylation inhibitor. VT103 inhibits YAP/TAZ-TEAD promoted gene transcription, blocks TEAD auto-palmitoylation, and disrupts interaction between YAP/TAZ and TEAD. VT103 can be used for the research of cancer[1].
CX-4945 is a potent, selective and oral casein kinase 2 (CK2) inhibitor with a Ki of 0.38 nM.
Galiellalactone is a is a small non-toxic and non-mutagenic fungal metabolite, a selective inhibitor of STAT3 signaling, with an IC50 of 250-500 nM. Galiellalactone can be used to research castration-resistant prostate cancer[1][2][3].
IWP-2-V2 is a IWP-2 (HY-13912) analogue that retains activity against the Wnt/β-catenin pathway[1].
Tyk2-IN-7 (Compound 48) is a TYK2 JH2 inhibitor, binds to TYK2 JH2 domain with IC50 and Ki.app of 0.00053 μM and 0.00007 μM, respectively. Tyk2-IN-7 (Compound 48) provides a highly selective alternative to conventional TYK2 orthosteric inhibitors, inhibits TYK2/JAK1/JAK2 kinase domain. Tyk2-IN-7 (Compound 48) provides robust inhibition in a mouse IL-12-induced IFNγ pharmacodynamic model as well as efficacy in an IL-23 and IL-12-dependent mouse colitis model[1].
Vismodegib (GDC-0449) is an orally active hedgehog pathway inhibitor with an IC50 of 3 nM. It also inhibits P-gp, ABCG2 with IC50 values of 3.0 μM and 1.4 μM, respectively.