PKA Inhibitor

BLU2864 is an orally active, highly selective, ATP-competitive PRKACA inhibitor (IC₅₀=0.3 nM). BLU2864 shows anti-tumor activity. BLU2864 can be used in cancer and polycystic kidney disease research.

PKA-IN-1 is a potent and selective cyclic AMP-dependent protein kinase (PKA) catalytic subunit (cAK) inhibitor with an IC₅₀ of 0.03 μM. PKA-IN-1 inhibits cAK in a fashion that is competitive with respect to ATP as substrate.

AT13148 is an orally active and ATP-competitive, multi-AGC kinase inhibitor with IC₅₀s of 38 nM/402 nM/50 nM, 8 nM, 3 nM, and 6 nM/4 nM for Akt1/2/3, p70S6K, PKA, and ROCKI/II, respectively.

LX7101 is a potent LIM-kinase, ROCK and PKA inhibitor with IC₅₀s of 24 nM, 1.6 nM, 10 nM and <1 nM for LIMK1, LIMK2, ROCK2 and PKA, respectively. LX7101 proves significantly selective for LIMK2 with IC₅₀ values of 4.3 nM and 32 nM for LIMK2 and LIMK1 at 2 μM ATP, respectively. LX7101 has the potential for ocular hypertension and associated glaucoma research.

Tetramisole hydrochloride is an orally active, selective inward rectifier potassium channel agonist with an EC₅₀ of approximately 30 μM for the Kir2.1 subunit. Tetramisole hydrochloride is also an anti-nematode agent that blocks neuromuscular transmission by non-competitive depolarization. Tetramisole hydrochloride promotes the forward transport of Kir2.1 channels, hyperpolarizes the resting potential (RP), shortens the action potential duration (APD), inhibits intracellular calcium overload and the PKA signaling pathway, and exerts anti-arrhythmic and anti-myocardial remodeling activities. Tetramisole hydrochloride can be used in cardiac electrophysiology research and research related to myocardial ischemia and heart failure.

ML281 is a highly selective inhibitor of serine/threonine kinase 33 (STK33) with an IC₅₀ value of 14 nM. ML281 shows 700-fold selectivity over PKA and 550-fold over AurB. ML281 exerts core mechanism by inhibiting STK33: in small cell lung cancer, ML281 downregulates RPS6/BAD signaling phosphorylation, induces apoptosis, and suppresses proliferation, invasion. ML281 reduces STK33-mediated 4-hydroxyphenylpyruvate dioxygenase (HPD) phosphorylation in tyrosinemia . ML281 is suitable for research on STK33 function, KRAS mutation-related cancers (pancreatic cancer, colon cancer, lung adenocarcinoma, etc.), small cell lung cancer, and tyrosinemia-related damage

HA-100 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 also used as a ROCK inhibitor.

Protein kinase inhibitor H-7 is a selective inhibitor of PKC and cyclic nucleotide-dependent protein kinases, with a K_i value of 6.0 μM for rabbit protein kinase C, a K_i value of 3.0 μM for rabbit cAMP-dependent protein kinase, and a K_i value of 5.8 μM for porcine cGMP-dependent protein kinase. Protein kinase inhibitor H-7 has no effect on Ca²⁺-calmodulin-dependent enzymes. Protein kinase inhibitor H-7 regulates the Actin cytoskeleton, inhibits contractility, disrupts stress fibers, induces protrusive activity, stabilizes intercellular junctions, and triggers rapid and reversible cytoskeletal reorganization. Protein kinase inhibitor H-7 serves as a research tool for elucidating the functions of protein kinase C-mediated signaling systems.

Linderane is an orally active natural sesquiterpene lactone with blood-brain barrier permeability. Linderane indirectly activates PDE3 by activating ERK/STAT3, thereby inhibiting the cAMP/PKA/CREB signaling pathway and hepatic gluconeogenesis. Linderane protects pancreatic β cells against oxidative damage by inhibiting the activation of the p38 MAPK pathway and activating the Nrf2 pathway. Linderane inhibits cell apoptosis and ameliorates intestinal mucosal inflammation by suppressing the IL-6/JAK/STAT3 signaling pathway. Linderane reduces pain sensitivity and alleviates anxiety-like behaviors by activating cannabinoid receptor 2 (CB2R). Linderane can be used in studies related to type 2 diabetes, ulcerative colitis, and chronic inflammatory pain with anxiety.

AT7867 dihydrochloride is a potent ATP-competitive inhibitor of Akt1/Akt2/Akt3 and p70S6K/PKA with IC₅₀s of 32 nM/17 nM/47 nM and 85 nM/20 nM, respectively.

Acenocoumarol is an anticoagulant that functions as a Vitamin K antagonist. Acenocoumarol inhibits MAPK/ERK/JNK signaling pathway, reduces the nuclear translocation of NF-κB p65, activates Akt/GSK3β signaling pathway. Acenocoumarol induces apoptosis in cell A549, arrests cell cycle at S phase.

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.

Sitagliptin-d₄ phosphate (MK-0431-d₄) is the deuterium labeled Sitagliptin phosphate (HY-13749A). 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.

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.