ATSP-9172 Provides First Demonstration of Direct and Specific Pharmacological Disruption of HIF/p300 Complex with Efficacy in Human Prostate Cancer Model
CAMBRIDGE, MA, USA I April 10, 2013 I Aileron Therapeutics, Inc. today announced new preclinical data demonstrating that ATSP-9172, its Stapled Peptide inhibitor of HIF-1α–dependent transcription, exhibits on-target binding activity, favorable pharmacokinetic properties and potent in vivo efficacy in a human prostate cancer model. These data will be presented today in a late-breaking poster presentation titled, “ATSP-9172, a novel Stapled Peptide inhibitor of HIF-dependent transcriptional activity with in vivo antitumor efficacy in a preclinical model of prostate cancer,” at the American Association for Cancer Research (AACR) Annual Meeting 2013, abstract number LB-304.
Expression of HIF-1α in a broad range of human cancers frequently correlates with poor patient prognosis, and there are currently no drugs that can directly and specifically inhibit HIF-1α-dependent transcription. ATSP-9172 is a Stapled Peptide drug candidate designed to mimic the structure and function of the CITED2 protein, a known negative regulator of HIF-1α. In this study, Aileron researchers showed that ATSP-9172 directly disrupts the HIF-1α /p300 interaction in cancer cells and specifically down-regulates the transcription of HIF-1α target genes without affecting off-target gene expression. The study further demonstrated favorable solubility and pharmacokinetic properties of high systemic exposure, low plasma clearance and long elimination half-life. Finally, dose-dependent inhibition of tumor growth in a human prostate cancer xenograft model was seen following intravenous administration of ATSP-9172 on an every other day schedule.
“We are pleased to share the first data supporting ATSP-9172 as a potent and specific oncology drug candidate targeting HIF-1α,” said Joseph A. Yanchik III, president and chief executive officer of Aileron Therapeutics. “HIF-1α is a key driver of tumor growth for many cancers, including prostate, breast, non-small cell lung and colorectal cancers. Despite its appeal as a target, HIF-1α has been undruggable by small molecule and biologic therapeutics, and our results to date with ATSP-9172 show our Stapled Peptide platform is uniquely suited to target this well-understood transcription factor for cancer therapy.”
Stapled Peptides are a new class of drugs with a unique set of properties that fully capitalize on 25 years of genetic research to attack drivers of complex diseases, including cancer, endocrine/metabolic disorders and inflammation. The Stapled Peptide platform locks peptides into their biologically active shape and imparts pharmaceutical stability within the body. Stapled Peptide drugs, like ATSP-9172, are derived from natural peptides and are designed to potently and specifically target protein-protein interactions both inside and outside the cell. This new class of drugs represents a fundamental scientific breakthrough as they offer the most advanced way to modulate signaling pathways to treat human disease.
About Aileron Therapeutics
Aileron Therapeutics is creating one of the first new classes of drugs in 20 years. Our proprietary Stapled Peptide drugs uniquely capitalize on 25 years of genetic research to attack the key drivers of complex diseases such as cancer, metabolic and endocrine conditions and inflammation. By harnessing one of the most common, but elusive, structures in nature – the alpha helical peptide – we believe that we can dramatically improve the treatment of these diseases and positively impact the lives of millions of patients. For more information, please visit www.aileronrx.com.
SOURCE: Aileron Therapeutics
Post Views: 96
ATSP-9172 Provides First Demonstration of Direct and Specific Pharmacological Disruption of HIF/p300 Complex with Efficacy in Human Prostate Cancer Model
CAMBRIDGE, MA, USA I April 10, 2013 I Aileron Therapeutics, Inc. today announced new preclinical data demonstrating that ATSP-9172, its Stapled Peptide inhibitor of HIF-1α–dependent transcription, exhibits on-target binding activity, favorable pharmacokinetic properties and potent in vivo efficacy in a human prostate cancer model. These data will be presented today in a late-breaking poster presentation titled, “ATSP-9172, a novel Stapled Peptide inhibitor of HIF-dependent transcriptional activity with in vivo antitumor efficacy in a preclinical model of prostate cancer,” at the American Association for Cancer Research (AACR) Annual Meeting 2013, abstract number LB-304.
Expression of HIF-1α in a broad range of human cancers frequently correlates with poor patient prognosis, and there are currently no drugs that can directly and specifically inhibit HIF-1α-dependent transcription. ATSP-9172 is a Stapled Peptide drug candidate designed to mimic the structure and function of the CITED2 protein, a known negative regulator of HIF-1α. In this study, Aileron researchers showed that ATSP-9172 directly disrupts the HIF-1α /p300 interaction in cancer cells and specifically down-regulates the transcription of HIF-1α target genes without affecting off-target gene expression. The study further demonstrated favorable solubility and pharmacokinetic properties of high systemic exposure, low plasma clearance and long elimination half-life. Finally, dose-dependent inhibition of tumor growth in a human prostate cancer xenograft model was seen following intravenous administration of ATSP-9172 on an every other day schedule.
“We are pleased to share the first data supporting ATSP-9172 as a potent and specific oncology drug candidate targeting HIF-1α,” said Joseph A. Yanchik III, president and chief executive officer of Aileron Therapeutics. “HIF-1α is a key driver of tumor growth for many cancers, including prostate, breast, non-small cell lung and colorectal cancers. Despite its appeal as a target, HIF-1α has been undruggable by small molecule and biologic therapeutics, and our results to date with ATSP-9172 show our Stapled Peptide platform is uniquely suited to target this well-understood transcription factor for cancer therapy.”
Stapled Peptides are a new class of drugs with a unique set of properties that fully capitalize on 25 years of genetic research to attack drivers of complex diseases, including cancer, endocrine/metabolic disorders and inflammation. The Stapled Peptide platform locks peptides into their biologically active shape and imparts pharmaceutical stability within the body. Stapled Peptide drugs, like ATSP-9172, are derived from natural peptides and are designed to potently and specifically target protein-protein interactions both inside and outside the cell. This new class of drugs represents a fundamental scientific breakthrough as they offer the most advanced way to modulate signaling pathways to treat human disease.
About Aileron Therapeutics
Aileron Therapeutics is creating one of the first new classes of drugs in 20 years. Our proprietary Stapled Peptide drugs uniquely capitalize on 25 years of genetic research to attack the key drivers of complex diseases such as cancer, metabolic and endocrine conditions and inflammation. By harnessing one of the most common, but elusive, structures in nature – the alpha helical peptide – we believe that we can dramatically improve the treatment of these diseases and positively impact the lives of millions of patients. For more information, please visit www.aileronrx.com.
SOURCE: Aileron Therapeutics
Post Views: 96
