Activators & Inhibitors

Activity: Autophagy inducer / inhibits glioblastoma growth . Function/Pharmacology: Itraconazole inhibits the conversion of lanosterol to ergosterol via inhibition of the 14-α demethylase, a cytochrome P-450 enzyme1. Clinically useful antifungal agent. It inhibits the proliferation of glioblastoma cells in vitro and in vivo by inducing autophagic progression via inhibiting the trafficking of cholesterol from late endosomes and lysosomes to the plasma membrane2. Inhibits the hedgehog pathway by binding to Smoothened (SMO) via a mechanism distinct from that of cyclopamine3. Inhibits angiogenesis via inhibiting the binding of VEGF to VEGFR24.

Activity: Anticonvulsant . Function/Pharmacology: Levetiracetam is a clinically useful non-classical anticonvulsant.1 It has no effect on voltage-dependent Na+ channels, GABAergic transmission, or affinity for either GABAergic or glutaminergic receptors.2,3 Levetiracetam is believed to act via binding to the synaptic vesicle protein SV2A.4 Levetiracetam reduced intra-neuronal Ca2+ levels by inhibition of ryanodine and IP3 receptor-dependent Ca2+ release from the endoplasmic reticulum.5 It was also observed to lower the pH of neocortical pyramidal cells via weakening of the transmembrane HCO3(-)-mediated acid-extrusion.6 Chemical Name: 2(S)-(2-Oxopyrrolidin-1-yl)butyramide

Activity: Neuropathic pain drug . Function/Pharmacology: Gabapentin is an approved drug for treatment of various types of neuropathic pain and some forms of epilepsy. The mechanism of action of gabapentin is not well understood. Despite being a structural mimic of GABA, it does not bind to GABA receptors at concentrations up to 1 mM.1,2 Some of its actions may be due to disrupting calcium channels.3 Chemical Name: 1-(Aminomethyl)cyclohexane

Activity: Calcium channel blocker / SARS-CoV2 3CLpro inhibitor . Function/Pharmacology: Manidipine is a clinically useful antihypertensive.1,2 It is an inhibitor of L- and T-type calcium channels with high selectivity for vasculature. Manidipine has recently been found to be an inhibitor (IC50 = 4.8 µM) of the SARS-CoV-2 main protease, 3CLpro.3 It also acts as an early entry inhibitor of human cytomegalovirus (EC50 = 3.57 µM) via inhibition of the Immediate-Early 2 (IE2) protein.4 Chemical Name: 5-O-[2-(4-Benzhydrylpiperazin-1-yl)ethyl] 3-O-methyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride

Activity: Transcription inhibitor, CK2 inhibitor . Function/Pharmacology: A classic inhibitor of transcription by RNA polymerase II. A relatively selective inhibitor of Cdk9 (IC50=3 μM), the kinase of the positive transcription elongation factor b (P-TEF-b) required for processive transcription elongation by RNA polymerase II.1,2 Also inhibits casein kinase II, IC50=4-10 μM. 3 Suppresses the SIRT1/CK2α pathway and enhances the radiosensitivity of human cancer cells.4 Kinase-independent activities of Cdk9 such as glucocorticoid receptor modulation are not inhibited by DRB.5 Chemical Name: 5,6-Dichloro-1-β-D-ribofuranosylbenzimidazole

Activity: Angiotensin II antagonist . Function/Pharmacology: Angiotensin II receptor I (AT1) antagonist, IC50s=1.12 and 2.86 nM for bovine adrenal cortex and rabbit aorta respectively.1 Selectively inhibits angiotensin II-induced contraction of rabbit aortic strips with no effect on contraction induced by other agents such as norepinephrine, KCl, serotonin, PGF2α or endothelin. Prevents astrocyte and microglial activation and neuroinflammation and improves hippocampal neurogenesis.2 Attenuates angiogenesis in hepatocellular carcinoma.3 Clinically useful antihypertensive agent. Ameliorates brain inflammation associated with Alzheimer’s disease.4 Active in vivo and orally active. Chemical Name: 2-Ethoxy-1-[[2’-(1H-tetrazol-5-yl)[1,1’-biphenyl]-4-yl]methyl]-1H-benzimidazole-7-carboxylic acid

Activity: Microtubule depolymerizer . Function/Pharmacology: Semisynthetic alkaloidal anticancer agent. Induces cell cycle arrest at G2/M phase by inhibiting mitotic spindle formation1. Inhibits normal microtubule assembly and induces aberant tubulin polymerization1. Induces apoptosis in a variety of cell lines2. Inhibits autophagosome maturation3. Inhibits palmitoylation of tubulin4.

Activity: Angiotensin antagonist . Function/Pharmacology: High affinity angiotensin AT1 receptor antagonist (Ki = 2.38 nM). Highly selective (30,000-fold) over AT2 receptors1,2. Normalizes the increased production of inflammatory cytokines in adipose and liver tissue in LPS-infused mice3. Clinically useful antihypertensive agent. Orally active. Chemical Name: (S)-3-methyl-2-[N-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-pentanamido]butanoic acid

Activity: Fluorescent DNA Probe . Function/Pharmacology: Fluorescent, intercalating DNA-binding agent useful for identifying apoptotic cells by flow cytometry.1,2 Capable of identifying populations representing live, apoptotic, and late apoptotic/dead cells in a quick, simple, reproducible, cost-effective fashion.3,4 Inhibitor of DNA-primed RNA polymerase and DNA polymerase.5