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Dr. Theresa  Phillips  Phd image

Dr. Theresa Phillips Phd

115 E Richmond Ave
Richmond CA 94801
510 376-6865
Medical School: Other - Unknown
Accepts Medicare: No
Participates In eRX: No
Participates In PQRS: No
Participates In EHR: No
License #: PSY 19723
NPI: 1932136108
Taxonomy Codes:
103T00000X

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Publications

Synthesis and evaluation of a novel series of indoloisoquinolines as small molecule anti-malarial leads. - Bioorganic & medicinal chemistry letters
A group of novel synthetic indoloisoquinolines was prepared and its potential as a novel series of small-molecule anti-malarial leads was assessed. The structure-activity relationship on variation of three distinct regions of chemical space was investigated. A lead compound was generated with an activity close to that observed for a known anti-malarial natural product, dihydrousambarensine, that shares the indoloisoquinoline template structure.Copyright © 2012 Elsevier Ltd. All rights reserved.
Fragment-based drug discovery applied to Hsp90. Discovery of two lead series with high ligand efficiency. - Journal of medicinal chemistry
Inhibitors of the chaperone Hsp90 are potentially useful as chemotherapeutic agents in cancer. This paper describes an application of fragment screening to Hsp90 using a combination of NMR and high throughput X-ray crystallography. The screening identified an aminopyrimidine with affinity in the high micromolar range and subsequent structure-based design allowed its optimization into a low nanomolar series with good ligand efficiency. A phenolic chemotype was also identified in fragment screening and was found to bind with affinity close to 1 mM. This fragment was optimized using structure based design into a resorcinol lead which has subnanomolar affinity for Hsp90, excellent cell potency, and good ligand efficiency. This fragment to lead campaign improved affinity for Hsp90 by over 1,000,000-fold with the addition of only six heavy atoms. The companion paper (DOI: 10.1021/jm100060b) describes how the resorcinol lead was optimized into a compound that is now in clinical trials for the treatment of cancer.
Discovery of (2,4-dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a novel inhibitor of the molecular chaperone Hsp90 by fragment based drug design. - Journal of medicinal chemistry
Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) are currently generating significant interest in clinical development as potential treatments for cancer. In a preceding publication (DOI: 10.1021/jm100059d ) we describe Astex's approach to screening fragments against Hsp90 and the subsequent optimization of two hits into leads with inhibitory activities in the low nanomolar range. This paper describes the structure guided optimization of the 2,4-dihydroxybenzamide lead molecule 1 and details some of the drug discovery strategies employed in the identification of AT13387 (35), which has progressed through preclinical development and is currently being tested in man.
Biodegradation of hexachlorocyclohexane (HCH) by microorganisms. - Biodegradation
The organochlorine pesticide Lindane is the gamma-isomer of hexachlorocyclohexane (HCH). Technical grade Lindane contains a mixture of HCH isomers which include not only gamma-HCH, but also large amounts of predominantly alpha-, beta- and delta-HCH. The physical properties and persistence of each isomer differ because of the different chlorine atom orientations on each molecule (axial or equatorial). However, all four isomers are considered toxic and recalcitrant worldwide pollutants. Biodegradation of HCH has been studied in soil, slurry and culture media but very little information exists on in situ bioremediation of the different isomers including Lindane itself, at full scale. Several soil microorganisms capable of degrading, and utilizing HCH as a carbon source, have been reported. In selected bacterial strains, the genes encoding the enzymes involved in the initial degradation of Lindane have been cloned, sequenced, expressed and the gene products characterized. HCH is biodegradable under both oxic and anoxic conditions, although mineralization is generally observed only in oxic systems. As is found for most organic compounds, HCH degradation in soil occurs at moderate temperatures and at near neutral pH. HCH biodegradation in soil has been reported at both low and high (saturated) moisture contents. Soil texture and organic matter appear to influence degradation presumably by sorption mechanisms and impact on moisture retention, bacterial growth and pH. Most studies report on the biodegradation of relatively low (< 500 mg/kg) concentrations of HCH in soil. Information on the effects of inorganic nutrients, organic carbon sources or other soil amendments is scattered and inconclusive. More in-depth assessments of amendment effects and evaluation of bioremediation protocols, on a large scale, using soil with high HCH concentrations, are needed.
Mineralization of hexachlorocyclohexane in soil during solid-phase bioremediation. - Journal of industrial microbiology & biotechnology
Soil containing hexachlorocyclohexane (HCH) was spiked with (14)C-gamma-HCH and then subjected to bioremediation in bench-scale microcosms to determine the rate and extent of mineralization of the (14)C-labeled HCH to (14)CO(2). The soil was treated using two different DARAMEND amendments, D6386 and D6390. The amendments were previously found to enhance natural HCH bioremediation as determined by measuring the disappearance of parent compounds under either strictly oxic conditions (D6386), or cycled anoxic/oxic conditions (D6390). Within 80 days of the initiation of treatment, mineralization was observed in all of the strictly oxic microcosms. However, mineralization was negligible in the cycled anoxic/oxic microcosms throughout the 275-day study, even after cycling was ceased at 84 days and although significant removal (up to 51%) of indigenous gamma-HCH (146 mg/kg) was detected by GC with electron capture detector. Of the amended, strictly oxic treatments, only one, in which 47% of the spiked (14)C-HCH was recovered as (14)CO(2), enhanced mineralization compared with an unamended treatment (in which 34% recovery was measured). Other oxic treatments involving higher amendment application rates or auxiliary carbon sources were inhibitory to mineralization. Thus, although HCH degradation occurs during the application of either oxic or cycled anoxic/oxic DARAMEND treatments, mineralization of gamma-HCH may be inhibited depending on the amendment and treatment protocol.
An evaluation on the level of retinoids in the bovine pineal body. - Advances in pineal research
Using high performance liquid chromatography, the level of retinoids was determined in the bovine pineal gland, retina, retinal pigment epithelium, cortical and subcortical brain tissues, skeletal muscle and the liver. Similar to the retina, the bovine pineal gland possesses levels of retinol and retinyl esters significantly higher than other brain tissues and muscle. These results are in agreement with the suggestion that the mammalian pineal gland and the retina may be of similar phylogenetic origin. However, unlike the retina, the bovine pineal gland does not possess any detectable level of retinal, the chromophore for visual pigments in the retina. This finding suggests that the bovine pineal gland does not possess rhodopsin nor the property of phototransduction which has been fully established in the retina and pineal glands of lower vertebrates.

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