Activators & Inhibitors

Activity: HDAC inhibitor . Function/Pharmacology: Potent HDAC inhibitor. Selective for HDAC1 (IC50 = 300 nM) over HDAC3 (IC50 = 8 µM) and HDAC8 (IC50 > 100 µM).1 In vivo, MS-275 has been shown to inhibit tumor growth via induction of the tumor supressors p21WAF1/CIP1 and gelsolin2 and to block cell proliferation in a variety of cancer cell lines3,4. The compound has also shown significant anti-rheumatic activity in rat and mouse arthritis models.5 Chemical Name: null

Activity: PKC inhibitor . Function/Pharmacology: Potent and selective PKCβ inhibitor. IC50 = 6, 39, 83 and 110 nM, for PKCβ, PKCα, PKCγ and PKCε respectively.1 Induces apoptosis in multiple myeloma cell lines via inhibition of the AKT signaling pathway.2 Induces mitotic missegregation and preferential cytotoxicity in colorectal cancer cells with chromosomal instability.3 Attenuates ampheta-mine-stimulated dopamine efflux.4 Inhibits blood-brain barrier leakiness in a mouse model.5 Chemical Name: 3-(1-Methyl-1H-indol-3-yl)-4-[1-[1-(2-pyridinylmethyl)-4-piperidinyl]-1H-indol-3-yl]-1H-pyrrole-2,5-dione

Activity: Microtubule stabilizing agent . Function/Pharmacology: Induces microtubule polymerization. Causes cell cycle arrest at the G2-M transition (EC50 = 32 nM for HeLa cells). Induces apoptosis. Cell permeable. Chemical Name: null

Activity: EGFR Kinase inhibitor . Function/Pharmacology: Potent inhibitor of EGFR tyrosine kinase (IC50 = 2 nM)1. Potent inhibitor of mutant JAK2-V617F2. Weaker inhibitor of ErbB-2 kinase (Ki = 1 μM) ErbB-4 kinase (Ki = 1.5 μM)3. HDAC inhibitors sensitize for erlotinib activity in EGFR-mutated and wildtype non-small cell lung cancer (NSCLC) cells4. A clinically effective agent for NSCLC5. Chemical Name: N-(3-Ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine hydrochloride

Activity: mTOR inhibitor . Function/Pharmacology: Semisynthetic analog of rapamycin with potent immunosuppressive activity1. Inhibits mTOR2 . Clinically useful immunosuppressant3. Chemical Name: 40-O-(2-Hydroxyethyl)rapamycin

Activity: ROCK inhibitor . Function/Pharmacology: Rho-associated kinase inhibitor (IC50 = 1.9 µM and 10.7 µM for Rho-associated kinase II and Rho-associated kinase respectively)1. Inhibits other kinases including cyclic nucleotide-dependent protein kinases.1 Reduces tryptamine-evoked vasopressor responses.2 attenuates bleomycin-induced pulmonary fibrosis in a mouse model.3 Clinically useful vasodilator. Chemical Name: 1-(5-Isoquinolinesulfonyl)homopiperazine HCl

Activity: Sphingosine-1-phosphate receptor agonist . Function/Pharmacology: An analog of sphingosine which, when taken up into cells, is phosphorylated and acts as an agonist at sphingosine-1-phosphate receptors (S1P1/3)1. Potently inhibits regulatory T cell proliferation in vitro and in vivo2. Enhances microvascular remodeling via expansion of arterioles and capillary networks3. Potent immunomodulator4. Chemical Name: 2-Amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol hydrochloride

Activity: Tyrosine kinase inhibitor . Function/Pharmacology: A naturally occurring flavonoid with a wide range of biological actions. Inhibits protein tyrosine kinases including epidermal growth factor receptor kinase.1,2 Phytoestrogen3 and agonist at GPR304. Displays cancer chemopreventive activity.5 Chemical Name: 5,7-Dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one

Activity: DNA polymerase inhibitor . Function/Pharmacology: Gemcitabine is a clinically useful anticancer agent.1 It exerts its cytotoxic effects via the metabolites gemcitabine diphosphate (dFdCDP) and gemcitabine triphosphate (dFdCTP). dFdCTP is an inhibitor of DNA polymerase and is also incorporated in DNA strands resulting in termination of chain elongation and apoptosis. dFdCDP is an inhibitor of ribonucleotide reductase which results in depletion of deoxyribonucleotides needed for DNA synthesis. Gemcitabine metabolites have also been reported to inhibit cytidine triphosphate synthetase (CTP synthetase)2 and deoxycytidylate deaminase (dCMP deaminase)3. Topoisomerase 1 has also been shown to be a target for gemcitabine.4 Chemical Name: 2’-Deoxy-2’,2’-difluorocytidine hydrochloride