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Eurand (Milan, Italy) (EURX) Presents at the 10th International Symposium on Antiangiogenic Agents
2/7/2008 9:16:28 AM
Jamaica Plain, MA, Feb. 7, 2008 -- Paloma Pharmaceuticals, Inc. today presented its work on
the Company’s PI3K/Akt/mTOR inhibitor Palomid 529 (P529) at the 10th International
Symposium on Anti-angiogenic Agents in La Jolla, California.
P529 is a non-steroidal, synthetic, small molecule anti-tumor agent created through
computational design, synthetic and medicinal chemistry, the result of three generations of
Palomid design work. Palomid’s broad activity as an anti-tumor agent is shown to reside in its
ability to target and inhibit the PI3K/Akt/mTOR signal transduction pathway as a dual
TORC1/TORC2 inhibitor.
“P529 is a potent anti-tumor agent acting through inhibition of the PI3K/Akt/mTOR pathway
targeting both TORC1 and TORC2 complexes. TORC1 inhibitors have already shown activity
in the clinic but their drawback is their lack of inhibition of signaling through TORC2. This
inability appears to be problematic as cancer cells may use the TORC2 signalling to evade
TORC1 antagonism resulting in tumor growth. P529 is unique and a first-in-class agent as it
works by eliminating presence of both complexes resulting in a thorough inhibition of
PI3K/Akt/mTOR signalling and interestingly enough does this without apparent systemic
toxicity,” said Dr. Sherris.
About the PI3K/Akt/mTOR Pathway
The PI3K/Akt/mTOR pathway has been implicated in a wide variety of biological responses
and is considered a major therapeutic target in cancer. Activation of this signaling pathway,
via direct or indirect mutagenic events, is common in many types of human cancer resulting in
deregulation of PI3K/Akt/mTOR pathway in cancer. Thus, agents capable of inhibiting the
PI3K/Akt/mTOR pathway are attractive targets for therapeutic intervention in cancer. Central
within the signalling pathway are two distinct protein complexes, one of which regulates growth
through the signal transduction protein S6K, TORC1, and the other that regulates cell survival
through Akt, TORC2. These complexes define both rapamycin-sensitive and insensitive
branches of the PI3K/Akt/mTOR pathway. Inhibition of the TORC2 pathway suppresses the
formation of tumors driven by the loss of the PTEN tumor suppressor, a gene which when lost
contributes to carcinogenicity. Inhibitors of TORC2 may then have beneficial effects as anticancer
agents without toxicity to normal tissues since loss of TORC2 through genetic alteration
does not appear to affect normal tissue. TORC1 antagonists as rapamycin and other such
rapalogs have shown activity in both animal models of cancer and in human clinical trials. As
inhibition of both TORC1 and TORC2 should result in more complete inhibition of
PI3K/Akt/mTOR signaling up-regulated in cancer, dual inhibitors are of active interest for
pharmaceutical development.
About Paloma Pharmaceuticals
Paloma Pharmaceuticals, Inc. is an early stage drug development company focusing on
cancer, ocular diseases (macular degeneration and diabetic retinopathy), arthritis, fibrotic
diseases (pulmonary fibrosis) endometriosis, osteoporosis and skin diseases (psoriasis and
atopic dermatitis). Paloma owns the intellectual property relating to a library of novel,
proprietary, small molecule drugs created through an integrated design platform incorporating
proprietary, customized and industry standard computational tools that has therapeutic
potential for the treatment of the foregoing diseases.
SOURCE Paloma Pharmaceuticals, Inc.
http://www.palomapharma.com.
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