Signal Pharmaceuticals Announces Positive Results In Preclinical Study Of Novel Drug Leads For Treatment Of Osteoporosis

December 04, 1998

San Diego, CA, December 4, 1998 -- Signal Pharmaceuticals today announced the successful completion of preclinical studies demonstrating the ability of two series of compounds to safely and effectively inhibit bone resorption in animal models of osteoporosis. The drug leads belong to a new class of small molecule compounds termed selective estrogen receptor modulators (SERMs), also referred to as 'designer estrogens.' SERMs are designed to mimic the positive effects of estrogen by inhibiting bone loss in postmenopausal women, while avoiding some of estrogen's adverse effects such as increased risk of breast and uterine cancer. Moreover, studies have demonstrated that some SERMs, such as Zeneca's tamoxifen (NolvadexTM) and Eli Lilly's raloxifene (EvistaTM), also have anti-estrogenic effects and therefore can be effective in preventing and treating breast cancer. Signal researchers are presenting data from successful preclinical studies at the joint meeting of The American Society for Bone and Mineral Research and The International Bone and Mineral Society being held in San Francisco, California, December 1-6.

Signal evaluated the efficacy of its novel SERMs in a rodent model of post-menopausal osteoporosis. Left untreated, these animals lose bone mass and eventually develop advanced stages of osteoporosis due to the loss of estrogen function. In the study, two series of drug leads were tested in parallel with estrogen and raloxifene for their ability to inhibit bone resorption. The study concluded that Signal's drug leads were twice as effective as raloxifene in preventing bone loss, at doses equal or less than raloxifene's therapeutic dose. In a separate study, these compounds also demonstrated superior safety, when compared with raloxifene, tamoxifen and estrogen, with regard to potential cancer risks in reproductive tissues. These drugs, if successfully developed, would provide clinicians with an alternative, non-estrogen treatment for osteoporosis that also would minimize some of the adverse effects associated with estrogen replacement therapy, including an increased risk for certain cancers.

Signal's President and CEO, Alan J. Lewis, Ph.D. commented, "Signal's integrated target and drug discovery capabilities allowed us to progress from lead discovery to lead development and in vivo efficacy in under a year. This is an impressive accomplishment given the complexity of this field of research. We believe these drug leads represent the 'third generation' of SERMs, combining the bone-protective effects of estrogen with a potentially improved safety profile."

Osteoporosis is an age-related disease that occurs primarily in post-menopausal women due to loss of estrogen. The disease is characterized by persistent loss of bone mass and afflicts more than 28 million people in the U.S. and over 200 million people worldwide, approximately 80% of whom are women. Estrogen-replacement therapy remains the primary treatment for pre- and post-menopausal women at risk for osteoporosis. However, this traditional hormone replacement therapy carries with it an increased risk of breast and uterine cancer. In December of 1997 the U.S. Food and Drug Administration (FDA) approved marketing of Eli Lilly's raloxifene, the first SERM with estrogen-like effects prescribed for the prevention of osteoporosis. While raloxifene represents an important advance in hormone replacement therapy for post-menopausal women, the drug is less potent than estrogen in inhibiting bone loss and does not prevent hot flashes.

Signal is developing new classes of small molecule drugs that potently and selectively control the mechanisms of bone disease at the level of gene function. Previously, Signal researchers identified a non-classical, estrogen-mediated gene regulation pathway that plays a fundamental role in regulating bone loss in women following menopause. In May of 1998, Signal was awarded a $750,000 Phase II SBIR grant from the National Institute of Diabetes and Digestive and Kidney Diseases to advance the Company's estrogen-mediated gene regulation program, including the preclinical development of novel classes of anti-resorptive SERM drugs for the treatment of osteoporosis. To expedite the discovery and validation of these drugs, Signal also developed a proprietary in vitro human bone model system that mimics the actual physiological environments of bone formation and bone resorption. The Company used this human bone model system, along with its high throughput screening and medicinal chemistry capabilities, to identify the two series of drug leads reported on today.

Signal has expanded its SERM gene regulation program to target and treat other estrogen-mediated diseases, particularly cancer. The Company recently completed a series of in vitro studies, both independently and in collaboration with the National Cancer Institute (NCI), that evaluated the anti-tumor effects of several newly discovered SERM drug leads. Both studies demonstrated significant anti-cancer effects in breast, renal, prostate and certain other tumor-types. These compounds are undergoing further evaluation at Signal and the NCI.

Signal Pharmaceuticals, Inc. is an integrated target and drug discovery company focused on identifying new classes of small molecule drugs that regulate genes and the production of disease-causing proteins. The Company applies advanced cellular, molecular and genomic technologies to map gene-regulating pathways in cells and to identify proprietary molecular targets that activate or deactivate genes and result in disease. Signal is advancing the application of genomics beyond identifying and elucidating the functions of genes to designing novel classes of disease-modifying drugs that selectively regulate the activation of disease-causing genes. The Company conducts its target and drug discovery programs both independently and with its five collaborative partners: Ares-Serono, Roche Bioscience, Nippon Kayaku, the Organon pharmaceutical division of Akzo Nobel and The DuPont Pharmaceutical Company.
Editor's Note: This release is also available on the internet at:

Noonan/Russo Communications

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to