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Development of Transporter Targeted Platinum Drugs for Glioblastoma

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43CA177013-01A1
Agency Tracking Number: R43CA177013
Amount: $216,990.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 102
Solicitation Number: PA15-269
Timeline
Solicitation Year: 2015
Award Year: 2016
Award Start Date (Proposal Award Date): 2016-09-07
Award End Date (Contract End Date): 2018-09-06
Small Business Information
67 JENNINGS LN, Atherton, CA, 94027-3017
DUNS: 078401096
HUBZone Owned: N
Woman Owned: Y
Socially and Economically Disadvantaged: N
Principal Investigator
 HUANCHIEH CHIEN
 (650) 361-1192
 apricity.therapeutics@gmail.com
Business Contact
 KATHLEEN GIACOMINI
Phone: (650) 361-1192
Email: apricity.therapeutics@gmail.com
Research Institution
N/A
Abstract
DESCRIPTION provided by applicant The blood brain barrier BBB the restrictive endothelium of the vasculature in the brain represents a major challenge for the development of drugs to treat disorders of the Central Nervous System CNS In particular many drugs cannot enter the brain because they are not able to cross the BBB However influx transporters in the BBB which facilitate the entry of essential nutrients and various endogenous molecules can be harnessed to deliver drugs to the brain Using knowledge of the transporters in the BBB we designed influx transporter targeted anti cancer drugs to treat an important and aggressive human cancer glioblastoma GB GB is the most malignant form of brain cancer that involves glial cells Overall the incidence is rare with people diagnosed in the US each year Platinum drugs are highly effective anti cancer drugs however have had limited use in cancers of the brain because of their inability to cross the BBB Preliminary studies suggest that our lead transporter targeted compound AT is highly potent in GB cell lines The major goal of this SBIR Phase I research is to establish proof of concept that the analogs form DNA adducts are dependent on transporters to enter the brain and the tumor and are efficacious in GB xenograft mouse models Two aims are proposed In studies under the first aim we will determine the potency of AT and a back up analog AT and measure the DNA adduct formation in ten GB cell lines with low and high grades of aggressiveness In the second aim we will establish efficacy in xenograft models of GB and determine the identity of the transporters that mediate the delivery of the compounds across the BBB The proposed studies will confer high commercialization potential for the two lead compounds since both analogs will be poised for critical Investigational New Drug IND enabling studies PUBLIC HEALTH RELEVANCE The proposed research focuses on the development of a new medicine for the treatment of a life threatening brain tumor glioblastoma If successful this research will lead to the development of a highly effective drug that is targeted to glioblastoma and designed to enter the brain The development of this medication will make an enormous contribution to the treatment of one of the most aggressive solid tumors in adults

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