Cytokinetics Announces Four Research Posters at the 46th Annual American Society for Cell Biology Meeting
The following posters were presented:
-- "A Novel Mechanism for Kinesin Spindle Protein (KSP) Modulation: Small
Molecular Activators of KSP Basal ATPase," was presented on Monday,
December 11, 2006. This presentation covered experiments focused to
developing a highly sensitive coupled enzymatic ADP formation assay.
This presentation concluded that the basal ATPase activity of KSP can
be screened using a sensitive readout of ADP generation yielding
several series of compounds that inhibit the basal and microtubule-
stimulated KSP ATPase activities. A series of compounds that activate
the KSP basal ATPase but inhibit its microtubule-stimulated ATPase
were demonstrated to cause mitotic arrest with monopolar spindles.
These compounds may represent a distinct means of perturbing KSP
function in spindle pole separation and mitotic progression.
-- "Functional Studies of Human Kip3D (Kif18A) Kinesin," was presented on
Monday, December 11, 2006. This presentation covered experiments
characterizing one member of the Kip3 family, human Kip3D. This
presentation concluded that Kip3D localizes to ends of mitotic spindle
microtubules and is a microtubule depolymerizing kinesin. Kip3D
function appears most important during mitosis, where siRNA knockdown
results in mitotic arrest and activation of Caspase 3 and possibly
apoptosis.
-- "Characterization of Motor-Domain Mutants of the Mitotic Kinesin
RAB6KIFL (MKLP2, KIF20A)," was presented on Monday, December 11, 2006.
This presentation covered experiments that engineered and
characterized three motor domain mutants of RAB6KIFL: T167N (P-loop),
R379A (Switch I), and G411A (Switch II), in order to explore the
relationship between the biochemical activity and biological function
of this motor protein. It was concluded that all three mutants lack
ATPase activity. In addition, T167N does not bind microtubules, while
binding by R379A and G411A is significantly different from the wild-
type protein. The wild-type and mutant constructs localize to the
central spindle microtubules. The R379A and G411A mutants, however,
are broadly distributed along the central spindle and not concentrated
in the midzone like the wild-type protein. This presentation
concluded that an inhibitor of the RAB6KIFL ATPase would be likely to
disrupt the recruitment to the central spindle of critical kinases
such as Plk-1 and Aurora-B.
-- "Effects of the Cardiac Myosin Activator CK-1316719 on Excitation-
Contraction (E-C) Coupling in Ventricular Myocytes," was presented on
Wednesday, December 13, 2006. This presentation covered experiments
that examined aspects of E-C coupling in adult rat cardiac myocytes
after treatment with the cardiac myosin activator CK-1316719. The
presentation concluded that CK-1316719 increases contractility in a
dose-responsive manner without increasing intracellular calcium,
without changing sarcoplasmic reticulum calcium content and without
altering the sodium calcium exchanger. These data support the
proposed mechanism of action of cardiac myosin activators, namely
increasing contractility by directly activating cardiac myosin, with
no effects on other aspects of E-C coupling including calcium
dynamics.
"We are pleased to have the opportunity to present these non-clinical data from our cell cycle control and contractility research programs," stated David J. Morgans, Jr., Ph.D., Cytokinetics' Senior Vice President of Drug Discovery and Development. "These presentations demonstrate our continuing efforts to maintain and strengthen our focus and advance our scientific insights in the area of cytoskeletal biology and pharmacology."
About Cytokinetics
Cytokinetics is a biopharmaceutical company focused on the discovery, development and commercialization of novel small molecule drugs that specifically target the cytoskeleton. The cytoskeleton is a complex biological infrastructure that plays a fundamental role within every human cell. Cytokinetics' focus on the cytoskeleton enables it to develop novel and potentially safer and more effective classes of drugs directed at treatments for cancer, cardiovascular disease and other diseases. Under a strategic alliance established in 2001, Cytokinetics and GlaxoSmithKline (GSK) are conducting research and development activities focused towards the potential treatment of cancer and other indications. Cytokinetics and GSK are continuing collaborative research focused to translational research directed to the mitotic kinesin centromere-associated protein E (CENP-E). GSK-923295, a CENP-E inhibitor, is being developed under the strategic alliance by GSK; GSK expects to begin clinical trials with GSK-923295 in 2007. Cytokinetics is responsible for the development of ispinesib and SB-743921, each a novel inhibitor of the mitotic kinesin KSP. Ispinesib has been the subject of a broad clinical trials program comprised of nine Phase II clinical trials as well as eight Phase I or Ib clinical trials. Cytokinetics plans to conduct additional clinical trials with ispinesib and is conducting a Phase I/II trial of SB-743921 in non-Hodgkin's lymphoma. Cytokinetics' unpartnered cardiovascular disease program is the second program to leverage the company's expertise in cytoskeletal pharmacology. Cytokinetics recently completed a Phase I clinical trial with CK-1827452, a novel small molecule cardiac myosin activator, and is advancing CK-1827452 in both intravenous and oral formulations for the treatment of heart failure. Additional information about Cytokinetics can be obtained at http://www.cytokinetics.com .
This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the "Act"). Cytokinetics disclaims any intent or obligation to update these forward-looking statements, and claims the protection of the Safe Harbor for forward-looking statements contained in the Act. Examples of such statements include, but are not limited to, statements relating to the expected initiation, timing and scope and targeted indications of clinical trials within Cytokinetics' and its partners' clinical development and research programs, the potential benefits of Cytokinetics' drug candidates and potential drug candidates and the enabling capabilities of Cytokinetics' biological focus. Such statements are based on management's current expectations, but actual results may differ materially due to various factors. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to decisions by GSK to postpone or discontinue research and/or development efforts for CENP-E under Cytokinetics' collaboration with GSK, difficulties or delays in patient enrollment for clinical trials, unexpected adverse side effects or inadequate therapeutic efficacy of Cytokinetics' drug candidates, and other potential difficulties or delays in development, testing, regulatory approval, production and marketing of Cytokinetics' drug candidates that could slow or prevent clinical development, product approval or market acceptance (including the risks relating to uncertainty of patent or trade secret protection for Cytokinetics' intellectual property, Cytokinetics' ability to obtain additional financing if necessary and unanticipated research and development and other costs), and changing standards of care and the introduction by others of products or alternative therapies for the treatment of indications currently or potentially targeted by Cytokinetics' drug candidates and potential drug candidates. For further information regarding these and other risks related to Cytokinetics' business, investors should consult Cytokinetics' filings with the Securities and Exchange Commission.