As International Vice President of Cancer Research at Glaxo Wellcome (now GSK) and Associate Division Director of Experimental Therapy at Burroughs Wellcome, Dr. Spector worked closely with all branches of drug development, including toxicology, clinical research, clinical pharmacology, marketing, regulatory, patents, analytical chemistry, process chemistry, and pharmaceutical formulations. He has also had many interactions with the FDA to advance the development of drug candidates.
As President of Spector Consulting Services, Dr. Spector continues to have broad-based interest in many therapeutic areas, including agents to treat cancer, viral and other infections, heart disease, depression, and pharmacodynamic disorders. Dr. Spector is currently Cheif Scientific Officer of Adherex Technologies and is leading the clinical trial of eniluracil/5-fluorouracil/leucovorin for metastatic breast cancer.
In addition to many other Projects, Dr. Spector was the International Project Leader for the following two compounds that evolved from personal initiatives within his research group.
Click here to view The Eniluracil Story
Eniluracil (776), a potentiator of the antitumor activity of 5-fluorouracil (5-FU): Eniluracil (5-ethynyluracil) inactivates uracil reductase (DPD), the enzyme that rapidly degrades 5-FU in cancer patients. Eniluracil thereby improve the efficacy, the therapeutic index, and the oral bioavailability of 5-FU in laboratory animals. The combination therapy (Cytefuran®) was developed for treatment of solid tumors. Clinical trials started in May 1994. Dr. Spector was the International Project Leader from the inception of the preclinical studies through the first eight months of Phase I clinical development stages. Initial clinical results are very promising. Dr. Spector remained active in this project until retirement and continued as consultant through 2001. In 2009, he was appointed The Chief Scientific Officer of Adherex Technologies, Inc., a company that is developing this therapy.
348U87, a potentiator of the antiviral efficacy of acyclovir: 348U87 is an inactivator of herpes ribonucleotide reductase that synergizes with acyclovir against wild type and acyclovir-resistant herpes simplex types I and II and varicella zoster viruses. Dr. Spector was Project Leader to develop this topical therapy from its inception through the IND submission in 1990 for pilot studies. A clinical trial for herpes labialis ending in August 1994 was negative. Additional trails are not being pursued.
Dr. Spector was a Project Team Member for the following drug development projects (currently inactive) that evolved from his research initiatives.
776C85, an inactivator of uracil reductase that protects mice from the hematological toxicity of AZT (Retrovir): 776C85 inactivated uracil reductase (DPD) and significantly ameliorated the anemia induced by AZT in mice and dogs. However, interest in developing this drug further was tempered by its lack of protection in monkeys.
Oxypurinol, an inhibitor of xanthine oxidase that protects ischemic tissues from reperfusion injury: The finding that oxypurinol could rapidly inhibit the generation of superoxide radicals from xanthine oxidase even in the presence of high concentrations of physiological substrates led to patent filings and the formation of a Project Team for drug development. A patent for the synergistic use of oxypurinol and tissue plasminogen activator (TPA) was also filed. Although initial studies in dogs showed significant cardiac protection by oxypurinol, later studies were less convincing and the Project was discontinued.
Analogs to lower LDL cholesterol: A compound was discovered that lowers LDL cholesterol by 50% and raises HDL cholesterol by 100% in monkeys. A formal program has been formed to determine the usefulness of this agent, but was discontinued after the Glaxo-Wellcome integration.