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PPMP as a Ceramide Catabolism Inhibitor for Chemotherapy

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
65244
Program Year/Program:
2003 / STTR
Agency Tracking Number:
CA102842
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
AVANTI POLAR LIPIDS, INC.
AVANTI POLAR LIPIDS, INC. 700 INDUSTRIAL PARK DRIVE ALABASTER, AL 35007
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2003
Title: PPMP as a Ceramide Catabolism Inhibitor for Chemotherapy
Agency: HHS
Contract: 1R41CA102842-01
Award Amount: $249,947.00
 

Abstract:

DESCRIPTION (provided by applicant): Our goal is to develop 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) as a clinical inhibitor of ceremide catabolism, in order to enhance the anti-cancer activity of the cytotoxic retinoid, fenretinide (4-HPR). We have reported that 4-HPR increased ceramide in numerous pediatric and adult solid cancer and leukemia cell lines in vitro. We have also reported that PPMP, an inhibitor of glucosylceramide synthase and l-O-acylceramide synthase, further increased ceramide and synergized 4-HPR cytotoxicity. We hypothesize that intravenous or oral formulations of PPMP can achieve plasma and tissue levels that inhibit ceramide catabolism in vitro. We hypothesize that PPMP will enhance the anti-cancer effect of 4-HPR with tolerable systemic toxicity in vivo. We will: AIM 1. Identify the stereoisomer of PPMP that most effectively inhibits ceramide catabolism and increases 4-HPR cytotoxicity. AIM 2. Develop a cGMP process, and produce PPMP for pre-IND studies. AIM 3. Formulate PPMP for intravenous and/or oral delivery. AIM 4. Perform small animal pharmacokinetic and toxicology studies to support a Phase II STTR application to support IND-directed toxicology studies and cGMP PPMP manufacture for Phase I clinical trial. 4-HPR+PPMP represents a novel, p53-independent chemotherapy that is based upon the generation and manipulation of ceramide in vivo.

Principal Investigator:

Barry J. Maurer
3236695663
BMAURER@CHLA.USC.EDU

Business Contact:


2056632494
Small Business Information at Submission:

Avanti Polar Lipids, Inc.
700 INDUSTRIAL PARK DR 700 INDUSTRIAL PARK DR Alabaster, AL 35007

EIN/Tax ID: 630790131
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Research Institution Information:
CHILDREN'S HOSPITAL LOS ANGELES
4650 SUNSET BLVD
LOS ANGELES, CA 90027
RI Type: Domestic nonprofit research organization