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Dr. Katrin  Seifert  Psyd image

Dr. Katrin Seifert Psyd

5995 Iris Parkway
Frederick CO 80530
303 204-4726
Medical School: Other - Unknown
Accepts Medicare: No
Participates In eRX: No
Participates In PQRS: No
Participates In EHR: No
License #: 3557
NPI: 1669665287
Taxonomy Codes:
103TH0004X

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Publications

Potent small molecule Hedgehog agonists induce VEGF expression in vitro. - Bioorganic & medicinal chemistry
Here, we describe the synthesis, SAR studies as well as biological investigations of the known Hedgehog signaling agonist SAG and a small library of its analogues. The SAG and its derivatives were analyzed for their potency to activate the expression of the Hh target gene Gli1 in a reporter gene assay. By analyzing SAR important molecular descriptors for Gli1 activation have been identified. SAG as well as compound 10c proven to be potent activators of VEGF expression in cultivated dermal fibroblasts. Importantly and in contrast to SAG, derivative 10c displayed no toxicity in concentrations up to 250 μm.Copyright © 2012 Elsevier Ltd. All rights reserved.
Synthesis and biological evaluation of SANT-2 and analogues as inhibitors of the hedgehog signaling pathway. - Bioorganic & medicinal chemistry
Hedgehog (Hh) signaling plays an important role in cell signaling of embryonic development and adult tissue homeostasis. In vertebrates, the hh gene encodes three different unique proteins: sonic hedgehog (Shh), desert hedgehog (Dhh) and indian hedgehog (Ihh). Disruption of the Hh signaling pathway leads to severe disorders in the development of vertebrates whereas aberrant activation of the Hh pathway has been associated with several malignancies including Gorlin syndrome (a disorder predisposing to basal cell carcinoma, medulloblastoma and rhabdomyosarcoma), prostate, pancreatic and breast cancers. In vivo evidence suggests the antagonism of excessive Hh signaling provides a route to unique mechanism-based anti-cancer therapies. Recently the small molecule SANT-2 was identified as a potent antagonist of Hh-signaling pathway. Here, we describe the synthesis, SAR studies as well as biological evaluation of SANT-2 and its analogues. Fifteen SANT-2 derivatives were synthesized and analyzed for their interference with the expression of the Hh target gene Gli1 in a reporter gene assay. By comparison of structure and activity important molecular descriptors for Gli inhibition could be identified. Furthermore we identified derivative TC-132 that was slightly more potent than the parent compound SANT-2. Selected compounds were tested for Hh related teratogenic effects in the small teleost model medaka. Albeit Gli expression has indicated a 16-fold higher Hh-inhibiting activity than observed for the plant alkaloid cyclopamine, none of the tested compounds were able to induce the cyclopamine-specific phenotype in the medaka assay.

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5995 Iris Parkway Frederick, CO 80530
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Nearby Doctors

630 Main St. Suite A
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