Chemicals

Chemically modified tetracyclines show activity in mammalian cell pathways and diseases related to cancer inflammation and neurodegenerative pathways. 4-Dedimethylaminosancycline (CMT-3 or COL-3) acts as matrix metalloproteinase (MT-MMP) inhibitor. It has been studied in disorders of collagen destruction excessive TNF activity excessive nitric oxide activity excessive IL-1 activity excessiuve activity of elastase bone loss protein degradation muscle wasting collagen glycosylation phospholipase A2 activity. In addition CMT-3 has been investigated for the treatment of aneurysms ulcerations periodontal disease diabetes scleroderma progeria cancer and diseases of bone marrow function and thrombocytopenia.Alternate names: CMT-3 COL-3 COL-3 Compound Incyclinide NSC-683551

5-Ketoclomazone inhibits 1-deoxy-D-xylulose 5-phosphate (DXP) synthase the first enzyme of the MEP pathway (non-mevalonate pathway) of isoprenoid biosynthesis.References1) Y. Matsue H. Mizuno T. Tomita et al. "The herbicide ketoclomazone inhibits 1-deoxy-D-xylulose 5-phosphate synthase in the 2-C-methyl-D-erythritol 4-phosphate pathway and shows antibacterial activity against Haemophilus influenzae" J. Antibiotics (2010) 63 583-588. DOI: 10.1038/ja.2010.100

The non-mevalonate or MEP pathway for isoprenoid biosynthesis is essential in gram-negative some gram-positive bacteria plants and protozoa making it an attractive pathway to target for antibiotics since mammals use the mevalonate pathway to synthesize isoprenoids. IspF is the fourth step in the pathway and converts diphosphocytidyl-2-methylerythritol 2-phosphate into 2-methylerythritol 2 4-cyclodiphosphate (cMEPP). IspF inhibitor 1 (compound 3 in Geist et al.) has low micromolar activity (IC50 = 6.1-32 μM) against the recombinant enzymes and inhibits the growth of P. falciparum in a red blood cell assay.ReferenceJ.G. Geist et al “Thiazolopyrimidine Inhibitors of 2-Methylerythritol 2 4-Cyclodiphosphate Synthase (IspF) from Mycobacteriumtuberculosis and Plasmodium falciparum” ChemMedChem 2010 5 1092-1101.

Compounds that target isoprenoid biosynthesis in plasmodium falciparum could be a welcome addition to malaria chemotherapy since the methylerythritol phosphate (MEP) pathway used by the parasite is not present in humans. MMV008138 targets the apicoplast of P. falciparum and that its target in the MEP pathway differs from that of Fosmidomycin. The active stereoisomer of MMV008138 was (1R 3S)-configured which was found to be crucial for inhibition of the parasite growth as a MEP pathway-targeting antimalarial agent. Recently some researchers have claimed that they identified the molecular target of MMV008138 as IspD the third enzyme of the MEP pathway.References1) Yao Zhong-Ke Krai Priscilla M. et al. “Determination of the active stereoisomer of the MEP pathway-targeting antimalarial agent MMV008138 and initial structure-activity studies.” Bioorganic & Medicinal Chemistry Letter 2015 25 1515-15192) Wu W. Herrera Z Ebert D. Baska K.; Cho S.H.; Derisi J. I.; Yeh E

FR900098 an analog of the naturally occurring antibiotic Fosmidomycin inhibits 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) an enzyme in the non-mevanolate pathway for isoprenoid biosynthesis. The non-mevanolate or MEP pathway is essential in gram-negative some gram-positive bacteria plants and protozoa making it an attractive pathway to target for antibiotics since mammals use the mevalonate pathway to synthesize isoprenoids. FR900098 is twice as effective as Fosmidomycin against P. faliciparum in vitro.References Powered by Bioz See more details on Bioz1) E. Iguchi et al. “Studies on new phosphonic acid antibiotics. II. Taxonomic studies on producing organisms of the phosphonic acid and related compounds” The Journal of Antibiotics 33 1980 19–23.2) H. Jomaa et al. “Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs.” Science 285 1999 1573-1576.3) T. Umeda et al. “Molecular Basis of Fosmidomycin’s action on

 The Collagen Hybridizing Peptides are products of 3-Helix Inc.The collagen hybridizing peptide (CHP) is a novel and unique peptide that specifically binds unfolded collagen chains both in vitro and in vivo [1 2 3]. By sharing the Gly-X-Y repeating sequence of natural collagen CHP has a strong capability to hybridize with denatured collagen chains by reforming the triple helical structure in a fashion similar to DNA fragments annealing to complementary DNA strands. CHP is extremely specific: it has negligible affinity to intact collagen molecules due to lack of binding sites and it is inert towards non-specific binding because of its neutral and hydrophilic nature.CHP is a powerful histopathology tool which enables straightforward detection of inflammation and tissue damage caused by a large variety of diseases as well as tissue remodeling during development and aging [3]. CHP robustly visualizes the pericellular matrix turnover caused by proteolytic migration of cancer cells

This novel and selective probe for hydrogen sulfide (H2S) 7-azido-4-methylcoumarin (AzMC) is useful for monitoring cystathionine B-synthase (CBS) catalyzed reactions which play a critical role in human sulfur metabolism. Deactivated CBS is characterized by high plasma levels of homocysteine and H2S resulting in clinical manifestations of numerous disease states. AzMC used as a fluorgenic probe and concurrent CBS activity can be used to select compounds for activation or inhibition of this enzyme and is suitable for high-throughput screening and the development of potential therapeutics. In addition AzMC has been used as a photoaffinitry probe for the substrate binding site of human phenol sulfotransferase (SULT1A-1 or P-PST-1).Featured in References1. M.K. Thorson T. Majtan J.P. Kraus A.M. Barrios "Identification of Cystathionine β-Synthase Inhibitors Using a Hydrogen Sulfide Selective Probe." Angewandte Chemie (Int. ed. Eng.) 2013 52 4641-4144. DOI: 10.1002/anie.20130084

C6NIB is a fluorescence turn-on sensor that is suited for trace vapor detection of hydrogen peroxide (H2O2). The sensor mechanism is based on H2O2-mediated oxidation of the boronate fluorophore C6NIB which is nonfluorescent in the ICT band but is strongly fluorescent upon conversion to the phenol (C6NIO). The fluorescence turn-on reaction is extremely sensitive towards H2O2 with no sensor response to other common reagents. The negligible fluorescence background of C6NIB combined with the high fluorescent emission of C6NIO makes it an ideal candidate for efficient sensing. Dispersing C6NIB with TBAH into a silica gel matrix produces a highly efficient sensor for vapor detection of H2O2 in terms of detection limit (2.9 ppb) and response time (1 sec. under 1 ppm H2O2).References:M. Xu J-M. Han et al.“A selective fluorescence turn-on sensor for trace vapor detection of hydrogen peroxide” Chem. Commun. 2013 49 11779-11781.

Hypoxia Inducible Factor (HIF) regulates responses to hypoxia and is comprised of two subunits alpha and beta. Upon cellular exposure to hypoxic conditions the HIF complex (alpha and beta subunits) is stabilized and binds to DNA transcriptionally activating genes linked to the cellular processes of angiogenesis and glucose metabolism1. Under normal conditions the HIF-alpha subunit is hydroxylated by the enzyme HIF-alpha prolyl hydroxylase (HIF-PH) leading to ubiquitylation of HIF-alpha and subsequent destruction2. DMOG (dimethyloxalylglycine) is a cell permeable competitive inhibitor of HIF-alpha prolyl hydroxylase (HIF-PH) leading to the stabilization of HIF and subsequent angiogenesis and glucose metabolism at concentrations between 0.1 and 1 mM3 4References1) Ivan M. K. Kondo et al. (2001). "HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing." Science 292(5516): 464-8.2) Jaakkola P. D. R. Mole et al. (2001). "Targeting of HI