Researchers at the University of California at San Diego (UCSD) are developing
alanosine as a potential treatment for
cancer [227466], [408222]. The compound was originally under development in collaboration with Triangle, which initiated its development in 1996 [227466], but later discontinued development of the compound [406677]. As of May 2001, UCSD's ongoing clinical trials of
alanosine included phase II trials for
non-small cell lung cancer (NSCLC) and phase I trials for
acute lymphoid leukemia (ALL), while a phase II trial for
glioma at UCSD had been suspended [408222].
Alanosine is an
amino acid analog originally derived from Streptomyces alanosinicus. It interferes with the de novo synthesis of
adenosine in both malignant and normal cells. In
cancer cells that lack methyladenosine
phosphorylase (MTAP, required in the salvage pathway),
alanosine should deprive such cells (but not normal cells) of de novo synthesized
adenosine [277968]. In early 1997, patients were being recruited for a phase II pilot efficacy trial of
alanosine as a treatment for
glioma and NSCLC, since a significant number of these
tumor types lack MTAP and, it was hoped, would therefore be sensitive to
alanosine [239280], [248260]. Phase I and II trials were completed in the 1980s by the NCI before they were discontinued because
alanosine caused toxicity typically associated with
chemotherapy, and did not produce significant response rates in common
tumors such as breast or
colon cancers. Researchers at UCSD found that some types of
cancer lack MTAP, which was responsible for
alanosine's previous clinical failure [227466]; phase II trials were being carried out at the university in 1997 [269338]. Triangle obtained an option for a worldwide license from the Regents of the University of California that expired in September 1998 (but had an option to extend the period for a further one year) [277968].