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Polo box PLK Inhibitors Target Tumors Resistant to ATP Competitive Compounds

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41CA213711-01A1
Agency Tracking Number: R41CA213711
Amount: $224,933.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NCI
Solicitation Number: PA16-303
Timeline
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-05-03
Award End Date (Contract End Date): 2019-04-30
Small Business Information
166 CABIN DR
Irmo, SC 29063-7756
United States
DUNS: 079204540
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 CAMPBELL MCINNES
 (803) 576-5684
 mcinnes@cop.sc.edu
Business Contact
 CAMPBELL MCINNES
Phone: (803) 338-6340
Email: mcinnes@ppipharma.com
Research Institution
 UNIVERSITY OF SOUTH CAROLINA
 
MCKISSICK - 1500 PENDLETON STREET
COLUMBIA, SC 29208-0001
United States

 Nonprofit college or university
Abstract

Polo like kinase PLK is a central player in regulating entry into and progression through
mitosis Many studies have validated PLK as an anti tumor drug target and its inhibition is
potently anti proliferative to cancer cells However recent data suggests that there are two
major disadvantages of the conventional approach to blocking the kinase activity of PLK First
both general kinome and PLK family specificity is an issue with ATP competitive compounds as
they commonly inhibit all paralogs in the Polo kinase family including PLK a known tumor
suppressor Second a recent study indicates that a single point mutant in the active site of
PLK Cys Val results in complete resistance to structurally distinct ATP competitive
inhibitors currently in clinical trials suggesting that the emergence of resistance in the clinic
against these agents is a near certainty Therefore a strategy different from targeting the
catalytic domains is urgently needed PPI Pharmaceuticals will develop PLK selective non
ATP competitive inhibitors as effective anti tumor therapeutics that retain activity against
active site mutants resistant to conventional kinase inhibitors Such compounds will have
significant potential for development as anti tumor agents with decreased likelihood of tumor
resistance and off target effects PPI Pharmaceuticals will develop PLK selective non ATP competitive inhibitors as
effective anti tumor therapeutics through the use of the REPLACE strategy These
compounds will retain activity against active site mutants resistant to conventional
kinase inhibitors Such compounds will have significant potential for development as anti
tumor agents with decreased likelihood of tumor resistance and off target effects

* Information listed above is at the time of submission. *

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