Sequent Development

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Pre-clinical studies of pharmacological activity in vitro provide initial screening of the therapeutic activity of new drugs. Studies are conducted at our facilities at the Institute of Pharmacology and Toxicology in Kiev, except for cancer screening which is conducted at IEPOR, the premier cancer research center of the former Soviet Union.

Screening for Antihypertensive, Cardiotonic, and Antihistaminic Activity (in vitro)

Study Code Study Name Study Purpose and Value Duration (weeks)

AHYPA1 Antihypwetensive activity Evaluation of compounds with potential antihypertensive activity in isolated vascular segments. 2

CTA ardiotonic activity Evaluation of compounds with potential cardiotonic activity using isolated perused (Langendorff) heart.(rats, guinea pigs). 2

BBA Beta blocking activity Evaluation of compounds with potential beta-blocking activity using guinea pig trachea. 2

ASA Antispasmodic activity Evaluation of compounds with potential antispasmodic activity using rabbit intestinal strips. 2

AHISA Antihistaminic activity Evaluation of compounds with potential antihistaminic using guinea pig trachea. 2

CCBA Calcium antagonists: calcium channel blocking activity Evaluation of compounds with potential in isolated segments of different vascular tissues. 2

VDA Vasodilator activity Evaluation of compounds with potential vasodilator activity in isolated segments of different vascular tissues. 2

Oncology screening is conducted using a panel of human cell lines of different origin. These studies are designed to identify the spectrum of cancer cells that are sensitive against the new drug and help to estimate the range of therapeutic doses for pre-clinical studies of pharmacological activity in vivo.

Screening for Anticancer Activity (in vitro)

Study Code Study Name Study Purpose and Value Duration (weeks)

SAA-I Screening of anticancer activity of test article against 8-10 human cancer cell lines. To examine the cytotoxicity of the test article (using MTT calorimetric assay) in a wide range of concentrations. 8-9

CAA-I Comparison of anticancer activity of new test article and known anticancer drug against two human cancer cell lines. To compare the cytotoxicity of both test article and known anticancer drug. To determine the dose of the test article for pre-clinical studies in vivo. 3-4

DDI-I Study the drug-drug interactions against two human cancer cell lines. To examine the influence of test article on the cytotoxicity of known anticancer drug (using MTT calorimetric assay). To estimate a potential modifications of tumor drug resistance and combined action of anticancer agents. 4-5

AAT-I Screening of anticancer and of antiangiogenic activity of test article against 8-10 human cancer cell lines To examine the cytotoxicity of the test article and its ability to inhibit secretion of pro-angiogenic vascular endothelial growth factor (VEGF) by cancer cells. 9-10

Sequent Development
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E: vladvinnitsky@sequentdevelopment.com