p21

BRK inhibitor P21d hydrochloride is a highly potent inhibitor of breast tumor kinase (BRK PTK6), displaying an IC50 of 30 nM, and effectively suppresses p-SAM68 with an IC50 of 52 nM. This compound serves as a valuable tool for evaluating BRK inhibitors' efficacy in xenograft breast tumor models, enabling in vivo activity assessment.

O6-Benzylguanine is a guanine analog with antineoplastic activity,and is a potent O6-alkylguanine DNA alkyltransferase (AGT) inactivator.

Perillyl Alcohol is a naturally occurring monoterpene related to limonene with antineoplastic activity. Perillyl alcohol (Isocarveol) inhibits farnesyl transferase and geranylgeranyl transferase, thereby preventing post-translational protein farnesylation and isoprenylation and activation of oncoproteins such as p21-ras, and arresting tumor cells in the G1 phase of the cell cycle.

5-Aminosalicylic Acid (5-ASA) is an anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE.

Aspirin (Acetylsalicylic Acid) is a COX inhibitor that inhibits COX1 and COX2 (IC50=5 210 μg mL) with selective, irreversible, and oral activity. Aspirin is also a histone deacetylase inhibitor that up-regulates the cell cycle blocking protein, p21. Aspirin has a variety of activities. Aspirin has anti-inflammatory, antipyretic and analgesic, and antiplatelet aggregation activities.

β-Carotene (Provitamin A) is a naturally-occurring retinol (vitamin A) precursor obtained from certain fruits and vegetables with potential antineoplastic and chemopreventive activities. As an anti-oxidant, beta carotene inhibits free-radical damage to DNA.

CP21R7 (CP21) is an effective and specific GSK3β inhibitor. It is used as an activator of stem cells prior to the induction of differentiation of stem cells to smooth muscle and endothelial cells. CP21R7 can be combined with BMP4 to commit human pluripotent stem cells to a mesodermal fate.

PF-3758309 hydrochloride (PF-03758309 hydrochloride) , is a PAK4 inhibitor, is also a n orally bioavailable small-molecule inhibitor of p21-activated kinase 4 (PAK4) with potential antineoplastic activity. PF-3758309 hydrochloride binds to PAK4, inhibiting PAK4 activity and cancer cell growth. PAK4, a serine/threonine kinase belonging to the p21-activated kinase (PAK) family, is often upregulated in a variety of cancer cell types and plays an important role in cancer cell motility, proliferation, and survival.

FRAX486 HCL is a potent p21-activated kinase (PAK) inhibitor with IC50 values of 14, 33, 39 and 575 nM for PAK1, PAK2, PAK3 and PAK4 respectively.

Inolitazone dihydrochloride is an effective, high-affinity PPARγ agonist; its biological activity is dependent on PPARγ (IC50:0.8 nM) to inhibit cell growth. Inolitazone dihydrochloride enhances the role of cell cycle kinase inhibitor p21 WAF1/CIP1.

G-5555 is a potent inhibitor of p21-activated kinase 1 (PAK1) (Kis: 3.7 nM and 11 nM for PAK1 and PAK2, respectively).

Vesnarinone (Arkin) (INN) is a mixed phosphodiesterase 3 inhibitor and ion-channel modifier that has modest, dose-dependent, positive inotropic activity, but minimal negative chronotropic activity. It also suppresses cell proliferation and induces apoptosis by inducing the expression of p21, an inhibitor of cyclin-dependent kinase activity in p53-mediated cell cycle arrest.

NP213 TFA is a rapidly acting and first-in-class synthetic antimicrobial peptide (AMP) with anti-fungal activity. It targets the fungal cytoplasmic membrane via membrane perturbation and disruption.

CP21 is an iron chelator that binds to iron in a 3:1 (ligand:iron) ratio. It is active against P. falciparum when used at concentrations of 10 and 100 µM. CP21 inhibits production of prostaglandin I2 induced by epinephrine, arachidonic acid, or A23187 in isolated rat aortic rings with IC50 values of 1.3, 1.3, and 1.4 mM, respectively. It inhibits glutamate-induced oxytosis, as well as decreases iodoacetic acid-induced cytotoxicity in an in vitro model of ischemia, in HT22 mouse hippocampal cells (EC50s = 13 and 9.5 µM, respectively). CP21 (200 mg/kg) increases the excretion of iron, but not copper, zinc, calcium, or magnesium, in rabbits.

R-HP210 inhibits LPS-induced transcription of several pro-inflammatory genes (IL-1β, IL-6 and COX-2). r-HP210 has an IC50 value of 3.80 μM for NF-κB-mediated bolus trans-suppression. r-HP210 does not induce trans-activation of glucocorticoids (GCs).

NP213 TFA, a novel, first-in-class synthetic antimicrobial peptide (AMP) with rapid anti-fungal action, targets the fungal cytoplasmic membrane, resulting in perturbation and disruption. It has been demonstrated to be effective and well-tolerated in treating nail fungal infections [1] [2].

HP210, a selective glucocorticoid receptor modulator (SGRM), can suppress IL-1β and IL-6 mRNA expression, suggesting its utility in investigating inflammation-related diseases [1].

AP39 is a compound used to increase hydrogen sulfide (H2S) levels within mitochondria; it consists of a mitochondria-targeting motif (triphenylphosphonium) coupled to an H2S-donating moiety (dithiolethione) by an aliphatic linker. AP219, as a control compound for AP39, contains the triphenylphosphonium scaffold but lacks the H2S-releasing portion.

NP213 is a rapidly acting synthetic antimicrobial peptide (AMP). NP213 is effective and well-tolerated in resolving nail fungal infections. NP213 has anti-fungal activities. NP213 targets the fungal cytoplasmic membrane and plays its role via membrane perturbation and disruption.

P21d hydrochloride is a potent and selective breast tumor Ki nase (Brk) inhibitor (IC50 = 30 nM). Exhibits >650-fold selectively for Brk over Aurora B Ki nase and Lck. Downregulates SNAIL protein, restores E-cadherin expression and suppresses migration in breast cancer cells. Also activein vivoand orally bioavailable.

S-HP210 is a selective and potent glucocorticoid receptor (GR) modulator that inhibits NF-κB transcription (IC50: 1.92 μM). S-HP210 is not toxic to mouse fibroblasts at effective doses of 3T3.

Theaflavin 3,3'-digallate (8-Gingerol) , a major polyphenol found in black tea, is an inducer of oxidative stress which has anti-inflammatory and cancer chemopreventive actions, it reduces tumor angiogenesis by downregulating HIF-1αand VEGF.

Pifithrin-α, p-Nitro, Cyclic (PFN-α) is a cell-permeable, active-form inhibitor of p53.

BIX-01294 trihydrochloride is an inhibitor of G9a histone methyltransferase.In a cell-free assay, the IC50=2.7 μM for G9a histone methyltransferase.

Naphthazarin (5,8-Dihydroxy-1,4-naphthoquinone) is effective by various cellular mechanisms including oxidative stress, activation of mitochondrial apoptosis-inducing factor (AIF), depolymerization of microtubules, interference with lysosomal function and p53-dependent p21 activation. It triggers apoptosis and has anti-tumor effects

Fingolimod (FTY-720A) is an antagonist of sphingosine 1-phosphate (S1P) (IC50 of 0.033 nM in K562 and NK cells).

Indisulam (E 7070) is a carbonic anhydrase inhibitor and antitumor CDK inhibitor that targets the G1 phase of the cell cycle by depleting cyclin E, inducing p53 and p21, and inhibiting CDK2, thereby causing a blockade in the G1 S transition.

NVS-PAK1-1 is an effective and selective allosteric PAK1 inhibitor (IC50: 5 nM).

1. Schisandrol B (Besigomsin) may exert neuroprotective effects by attenuating the microglia-mediated neuroinflammatory response via inhibiting the TLR4-mediated NF-κB and MAPKs signaling pathways. 2. Schisandrol B has anti-inflammatory property, potentially result from the inhibition of COX-2, iNOS, IL-6, TNF-α and NO through the down-regulation of RIP2 and NF-κB activation. 3. Schisandrol B induces marked protective effects against hepatic and renal injury induced by CCl(4) exposure through differential regulation of the MAPK signal transduction pathway. 4. Schisandrol B significantly inhibits cell proliferation in a dose-dependent manner, due to cell cycle arrest in the G1 phase with the downregulation of cyclin D1 expression and Retinoblastoma (RB) phosphorylation.

KCC-07 is a selective, potent and brain-penetrant inhibitor of methyl-CpG-binding domain protein 2(MBD2) with anticancer activity. KCC-07 prevents binding of MBD2 to methylated DNA and activates brain specific angiogenesis inhibitor 1 (BAI1) inducing anti

Fingolimod hydrochloride (FTY720) , a novel immune modulator, is a sphingosine 1-phosphate (S1P) antagonist (IC50: 0.033 nM in K562 and NK cells).

HNHA is an inhibitor of HDAC.

PF-3758309 (PF-03758309) (IC50=1.3 nM), a pyrrolopyrazole inhibitor of PAK4, has effective ATP-competition.

WS-383 is a selective, potent and reversible DCN1-UBC12 interaction inhibitor(IC50 of 11 nM).

GNE 2861 inhibits PAK4, PAK5, and PAK6 (IC50s: 7.5, 36, 126 nM, respectively). GNE 2861 is a PAK inhibitor that shows group II selectivity.

UC2288 is a relatively selective p21 attenuator which is synthesized based Sorafenib. UC2288 attenuates p21 protein levels with minimal effect on p21 protein stability.

LCH-7749944 (GNF-PF-2356) is a potent PAK4 inhibitor with an IC50 of 14.93 μM, effectively suppressing the proliferation of human gastric cancer cells by downregulating the PAK4 c-Src EGFR cyclin D1 pathway and inducing apoptosis.

G-5555 hydrochloride is a potent and selective p21-activated kinase 1 (PAK1) inhibitor with a Ki of 3.7 nM.

Pinoresinol ((+)-Pinoresinol) has antiinflammatory, hepatoprotective, and fungicidal activities, it can protect pial microcirculation from I-reperfusion injury, to increase nitric oxide release and to reduce oxidative stress preserving pial blood flow distribution; it may exert pharmacologically interesting effects via modulation of the insulin-like signalling pathway in C.elegans. Pinoresinol causes an upregulation of the CDK inhibitor p21(WAF1 Cip1) both at mRNA and protein levels, inhibits NF-kappaB and activating protein 1 (AP-1).

BIX-01294 is an G9a Histone Methyltransferase inhibitor(IC50 : 1.9 μM).

MRK003 is a γ-secretase inhibitor exhibits promising in vitro pre-clinical activity in multiple myeloma and non-Hodgkin's lymphoma. MRK003 treatment induced caspase-dependent apoptosis and inhibited proliferation of MM and NHL cell lines and patient cells. Examination of signaling events after treatment showed time-dependent decrease in levels of the notch intracellular domain, Hes1 and c-Myc. MRK003 downregulated cyclin D1, Bcl-Xl and Xiap levels in NHL cells and p21, Bcl-2 and Bcl-Xl in MM cells. In addition, MRK003 caused an upregulation of pAkt, indicating crosstalk with the PI3K/Akt pathway.

FRAX-1036 is a effective and selective PAK1 inhibitor.

USP7-IN-9, a potent inhibitor of ubiquitin-specific protease 7 (USP7) with an IC50 of 40.8 nM, effectively induces apoptosis and arrests cell progression at the G0/G1 and S phases in RS4;11 cells. It decreases the protein levels of oncoproteins MDM2 and DNMT1 while enhancing the levels of tumor suppressors p53 and p21.

Anticancer agent 70 (Compound 21) is a potent anticancer compound that demonstrates remarkable cytotoxicity against multiple human cancer cell lines. It induces G0/G1-cell cycle arrest and concurrently elevates the levels of p53 and p21 proteins. Furthermore, Anticancer agent 70 induces ATP depletion and disruption of the mitochondrial membrane potential [1].

MIR002 is a potent, orally active dual inhibitor of DNA polymerase α (POLA1) and HDAC 11 with significant in vivo antitumor activity. p53 acetylation, p21 activation, cell cycle arrest in G1/S phase, and apoptosis induction.

Hygrolidin is a macrocyclic lactone originally isolated from S. hygroscopicus. It inhibits proliferation of a variety of cancer cell lines, including DLD-1 colon cancer, LNCaP prostate cancer, and K562 leukemia cells (IC50s = 2.9, 5.2, and 33 ng/ml, respectively). Hygrolidin induces the expression and levels of p21 in DLD-1 cells, but not WI-38 fibroblasts, and leads to cell accumulation in the G1 and S phases without inducing apoptosis. It has antiparasitic activity against T. cruzi, L. donovani, and T. b. brucei but also induces cytotoxicity in HepG2 cells (IC50s = 1.1, 72.5, 77, and 24.5 nM, respectively).

MHY219 is a novel HDAC inhibitor. MHY219 induces apoptosis via up-regulation of androgen receptor expression in human prostate cancer cells. MHY219 was shown to enhance the cytotoxicity on DU145 cells (IC50, 0.36 μM) when compared with LNCaP (IC50, 0.97 μM) and PC3 cells (IC50, 5.12 μM). MHY219 showed a potent inhibition of total HDAC activity when compared with SAHA. MHY219 increased histone H3 hyperacetylation and reduced the expression of class I HDACs (1, 2 and 3) in prostate cancer cells. MHY219 effectively increased the sub-G1 fraction of cells through p21 and p27 dependent pathways in DU145 cells. MHY219 significantly induced a G2/M phase arrest in DU145 and PC3 cells and arrested the cell cycle at G0/G1 phase in LNCaP cells. Furthermore, MHY219 effectively increased apoptosis in DU145 and LNCaP cells, but not PC3 cells, according to Annexin V/PI staining and Western blot analysis. These results indicate that MHY219 is a potent HDAC inhibitor that targets regulating mu......

Neochamaejasmin A can inhibit cellular (3)H-thymidine incorporation (IC 50 12.5 microg/mL) and subsequent proliferation of human prostate cancer LNCaP cells, it blocks cell cycle progression at the G1 phase by activating the p21 protein and ultimately pro

AD4, an artemisinin derivative functioning as a proteolytic targeting chimera (PROTAC) for PCLAF, effectively degrades PCLAF in RS4;11 cells with an IC50 of 0.6 nM. This degradation activates the p21/Rb axis, resulting in antitumor activity. Furthermore, AD4 has been demonstrated to prolong survival in NOD/SCID mice transplanted with RS4;11 cells, showcasing its in vivo efficacy [1].

LAQ824 (Dacinostat (NVP-LAQ824)) is a novel HDAC inhibitor with IC50 of 32 nM and is an activator of the p21 promoter.