PKA Inhibitor

DS89002333 is an orally active and potent PRKACA inhibitor, with an IC₅₀ of 0.3 nM. DS89002333 shows good anti-tumor activity in an FL-HCC patient-derived xenograft model (expressing the DNAJB1-PRKACA fusion gene). DS89002333 can be used in study of fibrolamellar hepatocellular carcinoma (FL-HCC).

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.

Staurosporine (Standard) is the analytical standard of Staurosporine. This product is intended for research and analytical applications. Staurosporine is a potent, ATP-competitive and non-selective inhibitor of protein kinases with IC50s of 6 nM, 15 nM, 2 nM, and 3 nM for PKC, PKA, c-Fgr, and Phosphorylase kinase respectively. Staurosporine also inhibits TAOK2 with an IC50 of 3 μM. Staurosporine is an apoptosis inducer[1][2][3][4][5].

Rp-8-Br-cAMPS sodium is an analog of cAMP and an inhibitor of PKA. Rp-8-Br-cAMPS sodium occupies cAMP binding sites on PKA type I regulatory subunits, thereby preventing PKA dissociation and activation. Rp-8-Br-cAMPS sodium can be used in the study of tumors and retrovirus-induced immune deficiency. Rp-8-Br-cAMPS sodium also inhibits insulin secretion.

PKA Inhibitor Fragment (6-22) amide is a highly potent and specific competitive inhibitor of PKA, with K_i values of 1.7 nM and 1.6 nM against human and bovine PKA catalytic subunits, respectively. The IC₅₀ of PKA Inhibitor Fragment (6-22) amide targeting bovine PKA is 8.6 nM. PKA Inhibitor Fragment (6-22) amide effectively abolishes PKA activity in mouse brain and spinal cord, and exerts in vivo efficacy via intracerebroventricular administration. PKA Inhibitor Fragment (6-22) amide significantly reverses low-dose morphine analgesic tolerance in mice and blocks photoaffinity labeling of cAMP-dependent protein kinase. PKA Inhibitor Fragment (6-22) amide can be applied to research in fields related to the mechanism of morphine analgesic tolerance and skin wound healing.

Sitagliptin-d₄ hydrochloride is the deuterium labeled Sitagliptin hydrochloride (HY-13749E). Sitagliptin hydrochloride is an orally active and highly selective DPP4 inhibitor with an IC₅₀ value of 19 nM. Sitagliptin hydrochloride blocks the degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) by competing inhibition mechanism (Kᵢ = 1 nM), thereby increasing the level of active incretin. Sitagliptin hydrochloride can also directly stimulate the secretion of GLP-1 by intestinal L cells by activating the cAMP/PKA and ERK1/2 pathways, and this effect is independent of DPP-4. Sitagliptin hydrochloride shows protective effects on pancreatic islet grafts in 1-type diabetes models. Sitagliptin hydrochloride can be used for the study of 1-type and 2-type diabetes.

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 is an antagonist for calcium, that 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.

H-8 dihydrochloride is a selective Cyclic nucleotide-dependent protein kinase inhibitor. H-8 dihydrochloride potently inhibits cGMP- and cAMP-dependent protein phosphorylation. H-8 dihydrochloride enhances the vasodilatory effect induced by 8-bromo-cAMP (HY-12306A). H-8 dihydrochloride fails to attenuate the vasodilatory effects induced by 8-bromo-cGMP (HY-101379A), atrial natriuretic peptide II, or Sodium nitroprusside (HY-B0564) in rat aorta.

4-Ethylresorcinol is a derivative of resorcinol and can serve as a substrate for tyrosinase. 4-Ethylresorcinol has anti-hyperpigmentation and antioxidant effects and can inhibit melanin synthesis. 4-Ethylresorcinol has potential whitening value.

PF-4950834 is a potent, selective, orally bioavailable, ATP-competitive rho kinase inhibitor with IC₅₀ values of 8.35 nM and 33.12 nM against ROCK2 and ROCK1, respectively. PF-4950834 inhibits neutrophil migration.

KS-133 is a bicyclic peptide with VIPR2 antagonistic activity that can cross the blood-brain barrier. KS-133 selectively blocks VIPR2-mediated Gq/Ca, Gs/cAMP, cAMP/PKA/ERK and PI3K/AKT/GSK3β signaling pathways. KS-133 inhibits VIPR2 agonist-induced CREB phosphorylation in the prefrontal cortex of mice. KS-133 shifts the polarization direction of macrophages toward M1. KS-133 attenuates cancer cell proliferation and reduces the cell cycle distribution level at the S-M phase. KS-133 exerts antitumor effects in a mouse model of colorectal cancer. KS-133 reverses cognitive decline in mouse models of psychiatric disorders. KS-133 can be used for research related to schizophrenia, colorectal cancer and breast cancer.

UCN-02 (7-epi-Hydroxystaurosporine) is a selective protein kinase C (PKC) inhibitor with a PKC IC₅₀ value of 62 nM and a PKA IC₅₀ value of 0.25 μM. UCN-02 can be produced by Streptomyces strain N-126. UCN-02 can be used for the research of breast carcinoma.

STAD 2 is a potent and selective disruptor of PKA-RII, with a K_d of 6.2 nM. STAD 2 disrupts interactions between PKA and AKAP in an isoform-selective manner. STAD 2 displays antimalarial activity through a PKA-independent mechanism.

4-Methyloctanoic acid is an endogenous branched-chain medium-chain fatty acid and a negative regulator of the cAMP/PKA signaling pathway. 4-Methyloctanoic acid exerts antiepileptic effects by inhibiting epileptiform discharges and terminating behavioral and electroencephalographic seizures. 4-Methyloctanoic acid has neuroprotective effects; its polar metabolites can cross the blood-brain barrier, repair presynaptic release defects, improve motor function and alleviate neuromuscular degeneration in ALS models. 4-Methyloctanoic acid regulates phosphatidylinositol metabolism, reduces PIP/PIP₂ levels and increases inositol levels. 4-Methyloctanoic acid can be used in studies related to epilepsy and amyotrophic lateral sclerosis.

Midostaurin-d₅ (PKC412-d₅) is a deuterium labeled Midostaurin. Midostaurin is a multi-targeted protein kinase inhibitor which inhibits PKCα/β/γ, Syk, Flk-1, Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRβ and VEGFR1/2 with IC₅₀s ranging from 22-500 nM.

Fasudil (HA-1077; AT877) dihydrochloride is a nonspecific RhoA/ROCK inhibitor and also has inhibitory effect on protein kinases, with an K_i of 0.33 μM for ROCK1, IC₅₀s of 0.158 μM and 4.58 μM, 12.30 μM, 1.650 μM for ROCK2 and PKA, PKC, PKG, respectively. Fasudil dihydrochloride is also a potent Ca²⁺ channel antagonist and vasodilator.

Sitagliptin (MK-0431) phosphate (Standard) is the analytical standard of Sitagliptin phosphate (HY-13749A). This product is intended for research and analytical applications. Sitagliptin phosphate is an orally active and highly selective DPP4 inhibitor with an IC₅₀ value of 19 nM. Sitagliptin phosphate blocks the degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) by competing inhibition mechanism (Kᵢ = 1 nM), thereby increasing the level of active incretin. Sitagliptin phosphate can also directly stimulate the secretion of GLP-1 by intestinal L cells by activating the cAMP/PKA and ERK1/2 pathways, and this effect is independent of DPP-4. Sitagliptin phosphate shows protective effects on pancreatic islet grafts in 1-type diabetes models. Sitagliptin phosphate can be used for the study of 1-type and 2-type diabetes.

Akt1&PKA-IN-1 is a potent dual Akt/PKA inhibitor with IC₅₀ values of 0.03 , 0.11 μM, and 9.8 μM for PKAa, Akt, and CDK2, respectively. Akt1&PKA-IN-1 is selective for cyclin-dependent kinase 2 (CDK2).

A-3 hydrochloride is a potent, cell-permeable, reversible, ATP-competitive non-selective antagonist of various kinases. It against PKA (K_i=4.3 µM), casein kinase II (K_i=5.1 µM) and myosin light chain kinase (MLCK) (K_i=7.4 µM). A-3 hydrochloride also inhibits PKC and casein kinase I with K_i values of 47 µM and 80 µM, respectively.

β-Patchoulene is an orally active anti-inflammatory, antioxidant, and anti-apoptotic agent. β-Patchoulene inhibits the NF-κB, TLR4, and cAMP/PKA/CREB signaling pathways; activates the Sirt1/Nrf2 and AMPK signaling pathways; and targets Fas/FasL, Caspase-3, ERK1/2, ROCK1/MLC2 for inhibition. β-Patchoulene regulates cytokine secretion, inflammatory cell infiltration, lipid peroxidation, cell polarization, gut microbiota, and lipid metabolism, restores barrier function, mitochondrial function, and cell viability, and exhibits repellent activity against Spodoptera exigua larvae. β-Patchoulene can be used in research related to various inflammatory, ischemic, fibrosis-associated diseases, as well as hepatocellular carcinoma.