creb 1

CREB-IN-1 TFA is a potent and orally active CREB inhibitor with an IC50 of 0.18 μM, exhibiting inhibitory effects on the growth of breast cancer cells.

PI3K Akt CREB activator 1 (AE-18) is a selective inducible nitric oxide synthase (iNOS) inhibitor that crosses the blood-brain barrier, reduces infarct size and restores blood supply deficits after ischemia-reperfusion in rats, and is used in studies of vascular dementia and Parkinson's disease.

GNE-049 is a highly selective and potent inhibitor designed to target the CREB-binding protein (CBP) with high affinity, exhibiting an IC50 of 1.1 nM for the suppression of BRET and BRD4 activity, which consequently blocks prostate cancer cell proliferation in both in vitro and in vivo models.

Crebinostat is a potent histone deacetylase (HDAC) inhibitor, targeting HDAC1, HDAC2, HDAC3, and HDAC6 with IC50s of 0.7 nM, 1.0 nM, 2.0 nM, and 9.3 nM, respectively. It increases the density of synapsin-1 punctae along dendrites in neurons in vitro, modulates chromatin-mediated neuroplasticity, and enhances memory in mice. Additionally, Crebinostat induces histone H3 and H4 acetylation and enhances the expression of Egr1, a cAMP-responsive element binding protein (CREB) target gene.

Phanginin A, a potent and orally active activator of salt-induced kinase 1 (SIK1), effectively inhibits gluconeogenesis, increases the expression of p-SIK1, and decreases the expression of p-CREB. By reducing blood glucose levels and enhancing glucose tolerance and dyslipidemia, Phanginin A holds potential for type 2 diabetes research.

PF-CBP1 HCl is a highly selective inhibitor of the bromodomain of CREB-binding protein(CREBBP). It inhibits CREBBP (IC50: 125 nM) and p300 bromodomains (IC50: 363 nM).

PMED-1, a β-catenin inhibitor, effectively suppresses β-catenin activity in hepatoblastoma cells and various HCC (Hepatocellular Carcinoma) cells with IC50 values ranging from 4.87 to 32 μM. It impedes cell proliferation by disrupting the interaction between β-catenin and CREB-binding protein, thus affecting Wnt signaling pathways. PMED-1 is utilized in cancer research studies.

PDE4-IN-1 is a PDE4 inhibitor characterized by high potency (IC50: 8.6 nM) and superior selectivity over other PDE subtypes. This compound inhibits the release of inflammatory cytokines and chemokines. Additionally, PDE4-IN-1 significantly restores the damaged cAMP-CREB signaling pathway, inhibits proliferation, and promotes differentiation to reverse psoriasis formation.

CRT5, a pyrazine benzamide, is a potent and selective PKD inhibitor. It inhibits VEGF-induced phosphorylation of three PKD substrates (IC50s = 1, 2, and 1.5 nM for PKD1, PKD2, and PKD3, respectively), histone deacetylase 5, CREB (cAMP-response-element-binding protein), and HSP27 (heat-shock protein 27) at Ser82. Additionally, CRT5 decreases VEGF-induced endothelial migration, proliferation, and tubulogenesis[1].

KL044 is a cryptochrome 1 (CRY1) activator that prolongs circadian rhythms and inhibits PER2 activity. KL044 inhibits melanogenesis by inhibiting the cAMP PKA CREB pathway.

1. (±)-Praeruptorin A could exhibit its anti-osteoclastogenic activity by inhibiting p38 Akt-c-Fos-NFATc1 signaling and PLCγ-independent Ca(2+) oscillation 2. Praeruptorin A has the potential to inhibit migration fusion of preosteoclasts in vitro and bone erosion in vivo by targeting calmodulin and inhibiting the Ca(2+) calmodulin-CaMKIV-CREB-NFATc1 and or Ca(2+) calmodulin-calcineurin-NFATc1 signaling axis. 3. Praeruptorin A and praeruptorin C can significantly upregulate multidrug resistance-associated protein 2 expression via the constitutive androstane receptor-mediated pathway in vitro, and this should be taken as an herb-drug interaction.

DC-CPin7, a powerful inhibitor of the bromodomain of CREB-binding protein (CBP), exhibits an IC50 value of 2.5 μM [1].

Hcyb1 is a potent and specific inhibitor of phosphodiesterase 2 (PDE2). It exhibits a high degree of selectivity for inhibiting PDE2A with an IC50 value of 0.57 μM. In addition, Hcyb1 displays over 250-fold selectivity against other recombinant members of the PDE family. Moreover, its pharmacological actions include neuroprotective and antidepressant-like effects, which are believed to be mediated through the cAMP cGMP-CREB-BDNF signaling pathway [1].

DC-CPin711, a potent and selective inhibitor of the bromodomain of CREB-binding protein (CBP) with an IC50 of 0.0626 μM, effectively halts the cell cycle at the G1 phase and promotes apoptosis [1].

Sekikaic acid is a phenolic lichen metabolite that has been found in H. obscurata and has diverse biological activities. It scavenges superoxide and DPPH radicals in cell-free assays when used at a concentration of 0.5 µM. Sekikaic acid is active against the rg recombinant strain of respiratory syncytial virus (RSV; IC50 = 5.69 µg ml). It inhibits the protein-protein interaction between mixed lineage leukemia 1 (MLL1) and the GACKIX domain of CREB-binding protein (CBP; IC50 = 34 µM).

Insulin Detemir, an artificial insulin, effectively controls blood sugar levels by stimulating GLP-1 secretion through enhanced Gcg expression via the activation of Akt- and or extracellular signal-regulated kinase (ERK)-dependent-cat and CREB signaling pathways. It is applicable for type 2 diabetes research [1] [2].

4′-Demethylnobiletin, a bioactive metabolite, activates the PKA ERK CREB signaling pathway, enhances CRE-mediated transcription in hippocampal neurons, and reverses memory impairment linked to NMDA receptor antagonism through ERK signaling stimulation [1].

6-O-Isobutyrylbritannilactone, a sesquiterpene natural melanogenesis inhibitor, can be extracted from Inula britannica flowers. It effectively suppresses IBMX-induced melanin production in B16F10 cells and exerts antimelanogenic effects in zebrafish embryo models by modulating ERK, PI3K AKT, and CREB pathways [1].

Spadin TFA, a natural peptide originating from a propeptide in blood, acts as a powerful TREK-1 channel inhibitor with an IC 50 of 10 nM. It boosts dorsal raphe nucleus 5-HT neurotransmission in mice, activates hippocampal CREB, and promotes neurogenesis. This compound is useful for antidepressant research [1] [2].

Prolylserine, a dipeptide, acts as a melanogenesis inhibitor in Mel-Ab cells by reducing microphthalmia-associated transcription factor (MITF) and tyrosinase expression, inducing phosphorylation of ERK, but not affecting cAMP response element-binding protein (CREB) [1].

Compound F27 (Antileishmanial agent-19) is an antileishmanial compound effective against L. donovani promastigotes, demonstrating an IC50 of 3.39 μM. It functions by inhibiting the Leishmania prolyl-tRNA synthetase and disrupting the host PI3K Akt CREB axis-mediated IL-10 secretion. Additionally, Compound F27 promotes autophagy-mediated apoptosis in L. donovani promastigotes and has been shown to reduce parasite burden in L.d-infected animals [1].

Phoenixin-20 (PNX-20) is a vertebrate bioactive peptide with hormone-like actions, stimulating the hypothalamo-pituitary-gonadal axis to regulate mammalian reproduction, enhancing neuronal mitochondrial biogenesis via the CREB-PGC-1α pathway, and possessing an anxiolytic effect [1] [2] [3].

Phoenixin-20 (TFA) (PNX-20 (TFA)) is a bioactive peptide that stimulates hypothalamo-pituitary-gonadal hormones, regulates mammalian reproductive processes, enhances neuronal mitochondrial biogenesis via the CREB-PGC-1α pathway, and exhibits anxiolytic properties [1] [2] [3].

653-47 acts as a potentiator significantly enhancing the inhibitory activity of 666-15 on the cAMP-response element binding protein (CREB), while it also exhibits mild CREB inhibitory properties itself, with an IC50 value of 26.3 μM [1].