VALIDATION OF A NOVEL SARCOMERIC HIGH THROUGHPUT ASSAY

Information

  • Research Project
  • 6292378
  • ApplicationId
    6292378
  • Core Project Number
    R43HL066647
  • Full Project Number
    1R43HL066647-01
  • Serial Number
    66647
  • FOA Number
  • Sub Project Id
  • Project Start Date
    1/8/2001 - 23 years ago
  • Project End Date
    6/30/2001 - 23 years ago
  • Program Officer Name
    FAKUNDING, JOHN
  • Budget Start Date
    1/8/2001 - 23 years ago
  • Budget End Date
    6/30/2001 - 23 years ago
  • Fiscal Year
    2001
  • Support Year
    1
  • Suffix
  • Award Notice Date
    1/7/2001 - 23 years ago
Organizations

VALIDATION OF A NOVEL SARCOMERIC HIGH THROUGHPUT ASSAY

DESCRIPTION: (Investigator's abstract) The US. heart failure population numbers approximately 5 million and is growing. Despite treatment with current medical therapy, many patients remain symptomatic and require frequent hospitalization, placing an enormous burden on our health care system. Currently, the most ineffective arm of medical therapy are agents that modulate cardiac contractility. These agents improve patients' quality of life and decrease hospitalization rates, but have no effect on mortality rates. We propose to start development of a new class of cardiac contractility modulators acting directly on the force-producing cellular structure, the sarcomere. We will leverage Cytokinetics' robust high throughput screening technology to find compounds that modulate a reconstituted sarcomere. The ability to introduce a complex, well characterized, functional protein machine into a high throughput screen represents a significant advance in drug discovery. Using biochemical and physiological means, these compounds will be screened for secondary undesirable properties. This technology has already been validated against molecular motors that power mitosis. We expect to identify chemical compounds that have the potential to demonstrate proof of principle in relevant animal models. These compounds may eventually lead to a new class of contractility modulators that will play an important role in treating heart failure. PROPOSED COMMERCIAL APPLICATION: No new agents that modulate cardiac contractility have come on the market in nearly 10 years. The current market for digoxin, a 200 year old drug and the only one safe for chronic use in heart failure, is roughly $150 million per year (IMS data). The sales of non-generic dobutamine (Eli Lilly), used for acute heart failure, amounted to $86 million in 1998 (Paine Webber). Agents that directly target the force generating apparatus could be expected to be more effective and have fewer cellular toxicities. These properties may lead to improved patient outcomes. Naturally, such agents would gain a strong foothold in a large and growing marketplace.

IC Name
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
  • Activity
    R43
  • Administering IC
    HL
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    99900
  • Sub Project Total Cost
  • ARRA Funded
  • CFDA Code
    837
  • Ed Inst. Type
  • Funding ICs
    NHLBI:99900\
  • Funding Mechanism
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    CYTOKINETICS, INC.
  • Organization Department
  • Organization DUNS
  • Organization City
    SOUTH SAN FRANCISCO
  • Organization State
    CA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    94080
  • Organization District
    UNITED STATES