Stem cells are required for continuous tissue maintenance within diverse organs, stem cell activity is often externally dictated by the microenvironment (the niche) so that stem cell output is precisely shaped to meet homeostatic needs or regenerative demands. Several key signaling pathways have been shown to play essential roles in this regulatory capacity. Specifically, the JAK/STAT, Hedgehog, Wnt, Notch, Smad, PI3K/phosphatase and tensin homolog, and NK-κB signaling pathways have all been shown experimentally to mediate various stem cell properties, such as self-renewal, cell fate decisions, survival, proliferation, and differentiation.

Recent studies mainly focus on cancer stem cell, induced pluripotent stem cell, neural stem cell and maintenance of embryonic stem cell pluripotency. Cancer stem cells (CSCs) have been believed to be responsible for tumor initiation, growth, and recurrence. Numerous agents have been developed to specifically target CSCs by suppressing the expression of pluripotency maintaining factors Nanog, Oct-4, Sox-2, and c-Myc and transcription of GLI. Induced pluripotent stem cells (iPSCs) have the capacity to differentiate into various types of cells, and a self-renewing resource, and scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Novel pathological mechanisms have been elucidated, new drugs originating from iPSC screens are in the pipeline and the first clinical trial using human iPSC-derived products has been initiated.

References:
[1] Clevers H, et al. Science. 2014 Oct 3;346(6205):1248012.
[2] Matsui WH. Medicine (Baltimore). 2016 Sep;95(1 Suppl 1):S8-S19.
[3] Koury J, et al. Stem Cells Int. 2017;2017:2925869.
[4] Garg A, et al. Cells. 2017 Feb 2;6(1). doi: 10.3390/cells6010004.


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UCN-02

UCN-02 (7-epi-Hydroxystaurosporine) is a selective protein kinase C (PKC) inhibitor produced by Streptomyces strain N-12, with IC50s of 62 nM and 250 nM for PKC and protein kinase A (PKA), respectively. UCN-02 (7-epi-Hydroxystaurosporine) displays cytotoxic effect on the growth of HeLa S3 cells[1][2].

  • CAS Number: 121569-61-7
  • MF: C28H26N4O4
  • MW: 482.537
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BDP5290

BDP5290 is a potent inhibitor of both ROCK and MRCK with IC50s of 5 nM, 50 nM, 10 nM and 100 nM for ROCK1, ROCK2, MRCKα and MRCKβ, respectively.

  • CAS Number: 1817698-21-7
  • MF: C17H18ClN7O
  • MW: 371.82
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rho Kinase Inhibitor III,Rockout

3-(4-Pyridyl)indole (Rockout) is a Rho-kinase (ROCK) inhibitor, with an IC50 of 25 μM. 3-(4-Pyridyl)indole can inhibit blebbing and cause dissolution of actin stress fibers in a wound healing assay[1].

  • CAS Number: 7272-84-6
  • MF: C13H10N2
  • MW: 194.23200
  • Catalog: ROCK
  • Density: 1.211g/cm3
  • Boiling Point: 406.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 185.2ºC

C188-9

C188-9 is a Stat3 inhibitor, with a Kd of 4.7 nM.

  • CAS Number: 432001-19-9
  • MF: C27H21NO5S
  • MW: 471.524
  • Catalog: STAT
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 680.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 365.6±34.3 °C

GSK-3β inhibitor 13

GSK-3β inhibitor 13 (compound 47) is an orally active and potent GSK-3β inhibitor with blood-brain permeability. GSK-3β inhibitor 13 inhibits GSK-3β and GSK-3α with IC50s of 0.73 nM and 0.35 nM, respectively. GSK-3β inhibitor 13 significantly decreases the phosphorylation of tau (IC50=58 nM), which leads the formation of the neurofibrillary tangles associated with Alzheimer's disease[1].

  • CAS Number: 2227316-74-5
  • MF: C23H22N6O2
  • MW: 414.46
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TCS 21311

TCS 21311 (NIBR3049) is a potent, highly selective JAK3 inhibitor with an IC50 of 8 nM, it displays >100-fold selectivity over JAK1, JAK2 and TYK2. TCS 21311 (NIBR3049) inhibits PKCα, PKCθ, and GSK3β with IC50s of 13, 68, and 3 nM, respectively[1].

  • CAS Number: 1260181-14-3
  • MF: C27H25F3N4O4
  • MW: 526.50700
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-670462

PF-670462 is a potent and selective inhibitor of casein kinase (CK1ε and CK1δ), with IC50s of 7.7 nM and 14 nM, respectively.

  • CAS Number: 950912-80-8
  • MF: C19H22Cl2FN5
  • MW: 410.316
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SMO-IN-3

SMO-IN-3 (compound 12a) is a potent smoothened (SMO) inhibitor with an IC50 value of 34.09 nM for hedgehog (Hh) signaling pathway. SMO-IN-3 has antiproliferative activity against human medulloblastoma cell line Daoy. Anticancer activity[1].

  • CAS Number: 2376914-71-3
  • MF: C27H25F4N3O2
  • MW: 499.50
  • Catalog: Hedgehog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DCZ19931

DCZ19931 is a potent multi-targeting kinase inhibitor. DCZ19931 has anti-angiogenic effects on ocular neovascularization. DCZ19931 also inhibits ERK1/2-MAPK and p38-MAPK signaling[1].

  • CAS Number: 2789629-84-9
  • MF: C26H20F5N3O5
  • MW: 549.45
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AR-13503

AR-13503 a ROCK/PKC inhibitor, inhibiting angiogenesis and enhancing retinal pigment epithelium (RPE) permeability. AR-13503 also inhibits the formation of aberrant neovascularization (NV) in oxygen-induced retinopathy (OIR) model in mice[1][2].

  • CAS Number: 1254032-16-0
  • MF: C19H19N3O2
  • MW: 321.37
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Porcupine-IN-1

Porcupine-IN-1 is potent porcupine inhibitor with an IC50 of 0.5±0.2 nM.

  • CAS Number: 2036044-77-4
  • MF: C25H19FN4O
  • MW: 410.44
  • Catalog: Porcupine
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CX-4945 (sodium salt)

CX-4945 sodium salt is an orally bioavailable, highly selective and potent CK2 inhibitor, with IC50 values of 1 nM against CK2α and CK2α'.

  • CAS Number: 1309357-15-0
  • MF: C19H11ClN3NaO2
  • MW: 371.75200
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HA-100

HA-100 is an inhibitor of cGMP-dependent protein kinase (PKG), cAMP-dependent protein kinase (PKA), Protein kinase C (PKC) and MLC-kinase with IC50s of 4, 8, 12 and 240 μM, respectively.

  • CAS Number: 84468-24-6
  • MF: C13H15N3O2S
  • MW: 277.34200
  • Catalog: Myosin
  • Density: 1.332g/cm3
  • Boiling Point: 497.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 254.6ºC

Danvatirsen

Danvatirsen is an antisense oligonucleotide targeting STAT3 with potential antitumor activity. Danvatirsen binds to STAT3 mRNA, thereby inhibiting translation of the transcript. Suppression of STAT3 expression induces tumor cell apoptosis and decreases tumor cell growth.

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-04802367

A potent, highly selective GSK-3 inhibitor with IC50 of 2.1 nM for human GSK-3β in enzyme assays; shows equal effectivity against GSK-3α and GSK-3β with IC50 of 10.0 and 9.0 nM respectively in mobility shift assays, inhibits phosphorylation of tau with an IC50 of 466 nM in a stable inducible CHO cell line over-expressing GSK-3β and substrate tau; modulates tau phosphorylation in vitro and in vivo.

  • CAS Number: 1962178-27-3
  • MF: C16H16ClN5O3
  • MW: 361.786
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cardiogenol C

Cardiogenol C is a potent cell-permeable pyrimidine inducer which prompts the differentiation of ESCs into cardiomyocytes (EC50=100 nM)[1]. Cardiogenol C also acts cardiomyogenic on already lineage-committed progenitor cell types with a limited degree of plasticity. Cardiogenol C is a useful cardiomyogenic agent and can be used as a tool to improve cardiac repair by cell transplantation therapy in animal models[2].

  • CAS Number: 671225-39-1
  • MF: C13H16N4O2
  • MW: 296.753
  • Catalog: Wnt
  • Density: 1.305g/cm3
  • Boiling Point: 520.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 268.5ºC

Oct3/4-inducer-1

Oct3/4-inducer-1 (compound 2) is a potent Oct3/4 inducer. Oct3/4-inducer-1 promotes expression and stabilization of Oct3/4, and enhances its transcriptional activity in diverse human somatic cells[1].

  • CAS Number: 1016535-83-3
  • MF: C15H12FNO
  • MW: 241.260
  • Catalog: Oct3/4
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 391.7±27.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 190.7±23.7 °C

NVP-BSK805 trihydrochloride

NVP-BSK805 trihydrochloride trihydrochloride is an ATP-competitive JAK2 inhibitor, with IC50s of 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM for JAK2 JH1 (JAK homology 1), JAK1 JH1, JAK3 JH1, and TYK2 JH1, respectively[1].

  • CAS Number: 2320258-95-3
  • MF: C27H31Cl3F2N6O
  • MW: 599.93
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TGR-1202 Sulfate

Umbralisib sulfate is an orally active, potent and selective dual PI3Kδ and casein kinase-1-ε (CK1ε) inhibitor, with EC50 of 22.2 nM and 6.0 μM, respectively. Umbralisib sulfate exhibits unique immunomodulatory effects on chronic lymphocytic leukemia (CLL) T cells. Umbralisib sulfate can be used for haematological malignancies reseach[1][2][3][4].

  • CAS Number: 1532533-75-7
  • MF: C31H26F3N5O7S
  • MW: 669.62800
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 125 - 127 °C
  • Flash Point: N/A

IWP-O1

IWP-O1 is a highly potent Porcupine (Porcn) inhibitor, with an EC50 of 80 pM in L-Wnt-STF cells, suppressing the phosphorylation of Dvl2/3 and LRP6 in HeLa cells. IWP-O1 functions by preventing the secretion of Wnt proteins[1].

  • CAS Number: 2074607-48-8
  • MF: C26H20N6O
  • MW: 432.48
  • Catalog: Porcupine
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SAR407899 (hydrochloride)

SAR407899 hydrochloride is a selective, potent and ATP-competitive ROCK inhibitor, with an IC50 of 135 nM for ROCK-2, and Kis of 36 nM and 41 nM for human and rat ROCK-2, respectively.

  • CAS Number: 923262-96-8
  • MF: C14H17ClN2O2
  • MW: 280.75000
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hirsutenone

Hirsutenone is an active botanical diarylheptanoid present in Alnus species and exhibits many biological activities, including anti-inflammatory, anti-tumor promoting and anti-atopic dermatitis effects. Hirsutenone attenuates adipogenesis by binding directly to PI3K and ERK1 in a non-ATP competitive manner. Hirsutenone can be used for the study of obesity[1].

  • CAS Number: 41137-87-5
  • MF: C19H20O5
  • MW: 328.359
  • Catalog: ERK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 622.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 344.0±28.0 °C

CHIR-98014

CHIR-98014 is a potent, cell-permeable GSK-3 inhibitor with IC50s of 0.65 and 0.58 nM for GSK-3α and GSK-3β, respectively; it shows less potent activities against cdc2 and erk2.

  • CAS Number: 252935-94-7
  • MF: C20H17Cl2N9O2
  • MW: 486.314
  • Catalog: GSK-3
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 839.0±75.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 461.2±37.1 °C

TUL01101

TUL01101 is a potent, selective and orally active JAK1 inhibitor, with an IC50s of 3, 37, 1517 and 36 nM for JAK1, JAK2, JAK3, and TYK2, respectively. TUL01101 can be used for the research of rheumatoid arthritis[1].

  • CAS Number: 2411222-97-2
  • MF: C22H25F2N5O2
  • MW: 429.46
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TBB

TBB is a cell-permeable and ATP-competitive CK2 inhibitor with an IC50 of 0.15 μM for rat liver CK2.

  • CAS Number: 17374-26-4
  • MF: C6HBr4N3
  • MW: 434.708
  • Catalog: Casein Kinase
  • Density: 2.8±0.1 g/cm3
  • Boiling Point: 552.5±45.0 °C at 760 mmHg
  • Melting Point: 262-266ºC
  • Flash Point: 288.0±28.7 °C

JAK3-IN-6

JAK3-IN-6 is a potent, selective irreversible Janus Associated Kinase 3 (JAK3) inhibitor, with an IC50 of 0.15 nM.

  • CAS Number: 1443235-95-7
  • MF: C19H18N4O3
  • MW: 350.37
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

STAT3-IN-23

STAT3-IN-23 (PY*LKTK) is a potent STAT3 inhibitor[1].

  • CAS Number: 286465-26-7
  • MF: C36H61N8O12P
  • MW: 828.89
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H-9 dihydrochloride

H-9 Dihydrochloride is a PKA (protein kinase) inhibitor. H-9 Dihydrochloride (10 μM) significantly reduces the excitatory response to 5-HT. H-9 Dihydrochloride also has a direct effect on pharyngeal activity. H-9 Dihydrochloride inhibits signal-transduction and cell growth in EGF (epidermal growth factor)-dependent epithelial cell lines[1][2][3].

  • CAS Number: 116700-36-8
  • MF: C11H15Cl2N3O2S
  • MW: 324.227
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 250-255ºC dec.
  • Flash Point: N/A

KY02111

KY02111 is a small molecule which can promote differentiation of hPSCs to cardiomyocytes.IC50 value: Target: Wnt signaling inhibitorKY02111 Induces downregulation of Wnt signaling target genes; inhibits canonical Wnt signaling in a manner distinct from other known Wnt inhibitors.KY02111 (10 μM) increases the ratio of beating cardiac colonies as much as 70%-94% in cell aggregates of two hESC lines (KhES-1 and KhES-3), four hiPSC lines (253G1, IMR90-1, IMR90-4, and RCHIPC0003), and a mouse ESC line (R1). KY02111 (10 μM) results in 73%-85% postive IMR90-1 hiPSCs expressing the cardiac markers, cardiac troponin T (cTnT), αActinin, or NKX2.5, whereas only a few DMSO-treated cells are positive for the markers. KY02111 (10 μM) results in 16% postive IMR90-1 hiPSCs expressing the cardiac pacemaker marker, HCN4, whereas the ratio of Vimentin-positive cells (fibroblasts) decreases 3.3-fold. KY02111-induced cardiomyocytes (KY-CMs) expresses the cardiac markers, αMHC, NKH2.5, and HCN4, and that all of the ion channel genes examined are expressed at levels similar to those of adult heart tissue. KY02111 (10 μM) downregulates the expression of 72.7% target genes of canonical WNT signaling in IMR90-1 hiPSCs, suggesting that KY02111 inhibits canonical WNT signaling in hPSCs. KY02111 (10 μM) clearly reduces luciferase activities in both IMR90-1 hiPSCs and HEK293 cells in a dose-dependent manner in the TOPflash assay. KY02111 (10 μM-25 μM) increases cardiac differentiation about 80-fold in transgenic monkey ESCs compared to the control and does not show toxicity to cells even at high concentration. KY02111 (10 μM) significantly reduces luciferase activity in the TOPflash assay in SW480 cells, whereas XAV939 and IWP-2 does not. KY02111 (10 μM) dramatically reduces luciferase activity induced by GSK3β inhibitor BIO in SW480 cells, compared to that of XAV939 and IWP-2. KY02111 alone produces approximately 80% cTnT-positive cells, KY02111 in combination with other WNT inhibitors does not significantly increase differentiation efficiency, which shows that KY02111 effectively produces a high proportion of functional cardiomyocytes from hPSCs [1].

  • CAS Number: 1118807-13-8
  • MF: C18H17ClN2O3S
  • MW: 376.857
  • Catalog: Wnt
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cerdulatinib hydrochloride

Cerdulatinib hydrochloride (PRT062070) is a selective, oral active and reversible ATP-competitive inhibitor of dual SYK and JAK, with the IC50s of 32 nM, 0.5 nM, 12 nM, 6 nM and 8 nM for SYK and Tyk2, JAK1, 2, 3, respectively. Cerdulatinib hydrochloride could be used to research autoimmune disease and B-cell malignancies[1][2].

  • CAS Number: 1369761-01-2
  • MF: C20H28ClN7O3S
  • MW: 481.999
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A