Activators & Inhibitors

Activity: AMPK inhibitor . Function/Pharmacology: Potent, selective and ATP-competitive inhibitor of AMP-activated protein kinase (AMPK) (Ki = 109 nM).1 It displays no significant inhibition of ZAPK, SYK, PKCT, PKA and JAK3. It inhibits bone morphogenetic protein (BMP) type I receptors (ALK2, ALK3 and ALK6).2 Dorsomorphin has been shown to promote cardiomyogenesis in mouse embryonic stem cells (ESCs) in vitro.3 Induces autophagy in cancer cell lines via a mechanism independent of AMPK inhibition.4 Chemical Name: 6-[4-[2-(1-Piperidinyl)ethoxy]phenyl]-3-(4-pyridinyl)-pyrazolo[1,5-a]pyrimidine

Activity: c-Raf inhibitor . Function/Pharmacology: Potent and specific inhibitor of the protein kinase c-Raf (IC50=70nM). Has no significant effect on many other protein kinases tested (even at 50µM) with the exception of p38 (SAPK2α) (IC50=2µM) and SAPK2β (p38β) (IC50=2µM). Induces a paradoxical >100-fold activation of c-Raf in whole cells. Induces apoptosis in a variety of cell lines. Cell permeable. Chemical Name: 3-(Dimethylamino)-N-[3-[(4-hydroxybenzoyl)-amino]-4-methylphenyl]benzamide

Activity: c-Raf1 inhibitor . Function/Pharmacology: Potent inhibitor of cRAF1 kinase (IC50 = 9 nM). Displays 100-fold selectivity for cRAF1 over CDK1, CDK2, c-src, ERK2, MEK, p38, Tie2, VEGFR2 and c-fm. Displays neuroprotective effects In vivo via a mechanism that is independent of MEK, ERK, and Akt signaling. Cell permeable. Chemical Name: 3-(3,5-Dibromo-4-hydroxybenzylidene)-5-iodo-1,3-dihydroindol-2-one

Activity: BTK inhibitor . Function/Pharmacology: LFM-A13 is a selective inhibitor of Bruton’s tyrosine kinase (BTK) – IC50’s = 2.5 µM (recombinant BTK) and 17.2 µM (human BTK).1,2 It has also been shown to inhibit Polo-ilke kinase (PLK) – IC50 = 61 µM for human PLK3.3 It displayed no activity (concentrations up to 278 µM) at JAK1, JAK3, HCK, EGFRK and IRK2 or CDK1-3, CHK1, IKK, MAPK1, SAPK2a and ten tyrosine kinases3. Chemical Name: (2Z)-2-Cyano-N-(2,5-dibromophenyl)-3-hydroxy-2-butenamide

Activity: JNK inhibitor . Function/Pharmacology: Selective inhibitor of c-Jun N-terminal kinase (JNK). Reversibly inhibits JNK1,2 and 3 (IC50’s range from 40-90 nM). >300-fold selectivity for JNK as compared to related MAP kinases. Antiinflammatory activity. Inhibits expression of presenilin-1 and Notch signaling in mouse brain. Cell permeable and active in vivo. Chemical Name: Anthra[1-9-cd]pyrazol-6(2H)-one

Activity: VEGFR inhibitor . Function/Pharmacology: Inhibits VEGFR-1 (IC50 = 130 nM), VEGFR-2 (IC50 = 23 nM), and VEGFR-3 (IC50 = 18 nM). PDGFR-ß, cKit, and CSF-1R are also inhibited at higher concentrations (IC50’s 640 nM, 236 nM and 380 nM respectively). Screening studies have shown no inhibitory activity against a range of other kinases. X-Ray crystallography has shown that AAL-993 binds to the catalytic domain of VEGFR-2 when the protein is in an inactive conformation. Cell permeable, active in vivo and in whole animal studies. Chemical Name: 2-[(4-Pyridyl)methyl]amino-N-[3-(trifluoromethyl)phenyl]benzamide

Activity: PI 3-Kγ inhibitor . Function/Pharmacology: A potent, ATP-competitive, and isoform-selective PI3-Kinase inhibitor (IC50 = 0.07, 0.24, 1.45, and 1.70 µM for the ɣ, α, β, and δ isoforms respectively).1 Cell permeable. Chemical Name: 5-(1,3-benzodioxol-5-yl)methylidene-1,3-thiazolidine-2,4-dione

Activity: CAMKK inhibitor . Function/Pharmacology: Selective inhibitor of Ca2+-calmodulin-dependent protein kinase kinase (Ki = 80 and 15 ng/ml for inhibition of CaM-KKα and CaM-KKβ respectively).1 Binds to the ATP-binding site.2 Displays > 80-fold selectivity over CaMK1, CaMK2, CaMK4, MLCK, PKC, PKA and p42 MAPK. Important tool for probing distinct CaMK pathways in LTP.3 Reduces starvation-induced autophagosomal membrane formation.4 Reverses age-associated decline in bone mass.5 Stimulates osteoblast formation, inhibits osteoclast differentiation.6 Chemical Name: 7-Oxo-7H-benzimidazo[2,1-a]benz[de]isoquinoline-3-carboxylic acid acetate

Activity: Aurora B kinase inhibitor . Function/Pharmacology: ZM-447439 is a selective ATP-competitive inhibitor of Aurora kinase B1 (IC50 = 50 nM, Aur A IC50 = 1 µM, Aur C IC50 = 250 nM at physiological ATP concentrations2, Ref.1 lists Aur A IC50 = 110nM and Aur B IC50 = 113nM). It did not significantly inhibit a panel of 14 other kinases including mitotic kinases CDK1 and PLK1. It prevents chromosome alignment, spindle checkpoint function and cytokinesis.1,2 Chemical Name: N-[4-[[6-Methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinazolinyl]amino]phenyl]benzamide