Cardiogenol C hydrochloride is a cell-permeable pyrimidine compound which potently induces the differentiation of ESCs into cardiomyocytes (EC50= 100 nM).IC50 value: 100 nM (EC50)Target:in vitro: Cardiogenol C hydrochloride is a cardiomyogenesis inducer in embryonic stem cells. Cardiogenol C induces the differentiation of myosin heavy chain-positive cardiomyocytes from embryonic stem cells with an EC50 value of 0.1 μM; about 90% of embryonic stem cells treated with 0.25 μM of Cardiogenol C express the cardiac muscle cell specific transcription factors GATA-4, MEF2, and Nkx2.5 and display the characteristic beating behavior of differentiated cardiomyocytes. Cardiogenol C (a diaminopyrimidine) induces cardiac differentiation in P19 and in P19Cl6 cells. [1] Cardiogenol C could activate Wnt/β-catenin signaling to induce cardiogenesis. Cardiogenol C-treatment significantly decreased HBPCs proliferation. Cardiogenol C was able to induce HBPCs to transdifferentiate into cardiomyocyte-like cells.[2]
Hh-Ag1.5 (SAg1.5) is a potent Hedgehog (Hh) agonist with an EC50 of 1 nM[1]. Hh-Ag1.5 mediated reprogramming breaks the quiescence of noninjured liver stem cells for rescuing liver failure[2].
NMDAR/TRPM4-IN-2 free base (compound 8) is a potent NMDAR/TRPM4 interaction interface inhibitor. NMDAR/TRPM4-IN-2 free base shows neuroprotective activity. NMDAR/TRPM4-IN-2 free base prevents NMDA-induced cell death and mitochondrial dysfunction in hippocampal neurons, with an IC50 of 2.1 μM. NMDAR/TRPM4-IN-2 free base protects mice from MCAO-induced brain damage and NMDA-induced retinal ganglion cell loss[1].
ERK-IN-2 free base is a ERK2 inhibitor with an IC50 value of 1.8 nM. ERK-IN-2 free base might lead to off-target toxicity and/or off-target activity at dose >10 μM[1].
HA-100 dihydrochloride is a potent protein kinase inhibitor, with IC50s of 4 μM, 8 μM, 12 μM and 240 μM for cGMP-dependent protein kinase (PKG), cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and MLC-kinase, respectively. HA-100 dihydrochloride also used as a ROCK inhibitor[1][2].
ERK5-IN-2 is an orally active, sub-micromolar, selective ERK5 inhibitor with IC50s of 0.82 μM, 3 μM for ERK5 and ERK5 MEF2D, respectively. ERK5-IN-2 does not interact with the BRD4 bromodomain. ERK5-IN-2 suppresses both tumor xenograft growth and basic fibroblast growth factor (bFGF) driven Matrigel plug angiogenesis[1].
Niclosamide olamine is an anthelmintic that disrupts mitochondrial metabolism in parasitic worms and animal models. Niclosamide olamine inhibits STAT3 (IC50 = 0.25 μM) and stimulates autophagy by reversibly inhibiting mammalian target of Rapamycin complex 1 (mTORC1) signaling.
Larixol is an fMLP inhibitor and also inhibits Src kinase, ERK1/2, p38 and AKT phosphorylation signals in immune regulation. Larixol can interfere with the interaction between the βγ subunit of the fMLP receptor Gi protein and its downstream molecules, thereby inhibiting fMLP-induced respiratory burst. Larixol inhibits fMLP (0.1 μM)-induced superoxide anion production (IC50: 1.98 μM), cathepsin G release (IC50: 2.76 μM), and chemotaxis. Larixol improves neutrophil hyperactivation and reduces inflammation or tissue damage. A series of Larixol derivatives were found to have inhibitory effects on FSGS-related TRPC6 functional mutants[1][2].
STX-0119 is a selective, orally active STAT3 dimerization inhibitor. STX-0119 inhibits STAT3 transcription with an IC50 of 74 μM[1].
ABC1183 is a potent, selective, orally active GSK3α/β and CDK9 inhibitor with IC50 of 327/657 nM and 321 nM (CDK9/cyclin T1), shows growth inhibitory activity against a broad panel of cancer cell lines; decreases cell survival through G2/M arrest and modulates oncogenic signaling through changes in GSK3, GS and β-catenin phosphorylation and MCL1 expression; suppresses tumor growth and inflammation-driven gastrointestinal disease symptoms without organ or hematological toxicity in vivo.
Kemptide is a synthetic heptapeptide that acts as a specific substrate for cAMP-dependent protein kinase (PKA).
GSK3-IN-4 (compound 0715) is a potent GSK3 inhibitor. GSK3-IN-4 can be used for psychiatric disorder research[1].
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.
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].
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].
Pamidronic acid is a drug used to treat a broad spectrum of bone absorption diseases.
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].
6-O-Isobutyrylbritannilactone is a natural melanogenesis inhibitor. 6-O-Isobutyrylbritannilactone, a sesquiterpene, can be isolated from the flowers of Inula britannica. 6-O-Isobutyrylbritannilactone inhibits IBMX (HY-12318)-induced melanin production in B16F10 cells. 6-O-Isobutyrylbritannilactone also regulates ERK, PI3K/AKT, and CREB, shows antimelanogenic activity in zebrafish embryos models[1].
Rp-8-CPT-cAMPS, a cAMP analog, is a potent and competitive antagonist of cAMP-induced activation of cAMP-dependent PKA I and II. Rp-8-CPT-cAMPS preferentially selects site A of RI compares to site A of RII and site B of RII compares to site B of RI[1][2].
Gandotinib (LY2784544) is a potent JAK2 inhibitor with IC50 of 3 nM. Gandotinib (LY2784544) also inhibits FLT3, FLT4, FGFR2, TYK2, and TRKB with IC50 of 4, 25, 32, 44, and 95 nM.
SIS3 free base is a potent and selective inhibitor of TGF- beta1-induced Smad3 phosphorylation with an IC50 of 3 μM. SIS3 free base increases luciferase activity of p3TP-lux by abrogating the overexpression of constitutively active form of ALK-5[1].
Ipivivint, a first-in-class, orally active and potent CDC-like kinase (CLK) inhibitor, inhibits CLK1 (IC50=1.4 μM), CLK2 (IC50=0.002 μM) and CLK3 (IC50=0.022 μM). Ipivivint reduces Wnt pathway signaling gene expression through inhibiting CLK activity and serine and arginine rich splicing factor (SRSF) phosphorylation and disrupting spliceosome activity. Ipivivint can be used for the research of cancer[1].
JAK-IN-26 (compound 2) is an orally active JAK inhibitor with good pharmacokinetic characteristics. JAK-IN-26 inhibits IFN-α2B-induced phosphorylation of STAT3 in Jurkat cells (IC50=17.2 nM)[1].
TDZD-8 is an inhibitor of GSK-3β, with an IC50 of 2 μM; TDZD-8 shows less potent activities against Cdk-1/cyclin B, CK-II, PKA, and PKC, with all IC50s of >100 μM.
PKI(5-24) is a potent, competitive, and synthetic peptide inhibitor of PKA (cAMP-dependent protein kinase), with a Ki of 2.3 nM. PKI(5-24) corresponds to residues 5-24 in the naturally occurring heat-stable protein kinase inhibitor[1][2].
GSK-3β inhibitor 12 (compound 15) is an inhibitor of GSK-3β. GSK-3β inhibitor 12 inhibits 49.11% and 37.11% activity of 25 μM and 50 μM GSK-3β, respectively. GSK-3β inhibitor 12 can be used for the research of neurodegenerative diseases[1].
Fasudil is a potent inhibitor of ROCK1, PKA, PKC, and MLCK with Ki of 0.33 μM, 1.0 μM, 9.3 μM and 55 μM, respectively.