Rucaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of advanced mutant BRCA ovarian cancer. Rucaparib is being investigated in clinical trials against prostate cancer, breast cancer and other neoplasms.

The dihydrochloride salt of nolatrexed, a water-soluble lipophilic quinazoline folate analog with antineoplastic activity. Nolatrexed occupies the folate binding site of thymidylate synthase, resulting in inhibition of thymidylate synthase activity and thymine nucleotide synthesis with subsequent inhibition of DNA replication, DNA damage, S-phase cell cycle arrest, and caspase-dependent apoptosis. This agent also exhibits radiosensitizing activity. Orphan designation of nolatrexed was granted in the Unites States of America for treatment of hepatocellular carcinoma.

Metesind (AG-331) is a lipophilic thymidylate synthase inhibitor. It inhibits the cofactor binding site of the enzyme. It exerts cytotoxic properties. Metesind was being developed as an anticancer and antimetabolite agent.

Rupintrivir is a peptide aldehyde that targets the human rhinovirus (HRV) 3C proteinase enzyme and has the potential for the treatment of the common cold. Rupintrivir is derived from AG-6084 - in order to develop human rhinovirus 3C protease inhibitors with improved pharmacological properties, Agouron replaced the backbone amide moiety of the series which yielded AG-6084, with a ketomethylene isostere. A phase II efficacy study has been completed in healthy patients infected with the rhinovirus. Ruprintrivir was well tolerated; blood-tinged mucus and nasal passage irritation were the most common adverse effects reported. Pharmacokinetic analysis of plasma and nasal ruprintrivir concentrations revealed intranasal drug residence with minimal systemic absorption. The fact that rupintrivir is active against noroviruses belonging to genogroup I (Norwalk virus), genogroup V (murine norovirus), and the recombinant 3C-like protease of a GII norovirus suggests that the drug exerts cross-genotypic anti-norovirus activity and will thus most likely be effective against the clinically relevant human norovirus strains. Rupintrivir is also a high affinity inhibitor of Enterovirus-71 3C protease.

Prinomastat is a synthetic hydroxamic acid derivative with potential antineoplastic activity. Prinomastat inhibits matrix metalloproteinases (MMPs) (specifically, MMP-2, 9, 13, and 14), thereby inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis. As a lipophilic agent, prinomastat crosses the blood-brain barrier. Pfizer conducted multicenter, randomized, double-bind, placebo-controlled trials to evaluate the safety and efficacy of prinomastat in combination with standard chemotherapy in patients with advanced hormone refractory prostate cancer and non-small cell lung cancer. However, this study has been terminated for the reason that Prinomastat did not improve the outcome of chemotherapy in non-small cell Lung cancer patients.

Agouron (Pfizer) was developing AG-24322 (AG-024322), a small-molecule cyclin-dependent kinase (CDK) inhibitor, for the treatment of cancer. AG-024322 is a potent inhibitor of CDK1, CDK2, and CDK4 that produces cell-cycle arrest and antitumor activity in preclinical models. AG-24322 is a potent ATP-competitive inhibitor of CDK1, CDK2, and CDK4 with Ki values in the 2–3 nM range and selectivity over other non-CDKs. This compound has been shown to inhibit Rb phosphorylation in cells, elicit cell-cycle arrest, and have antiproliferative activity in multiple human tumor cell lines (IC50 values from 30 to 200 nM). AG-24322 was reported to be undergoing phase I trials for cancer in the US, however the development was discontinued.

Rucaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of advanced mutant BRCA ovarian cancer. Rucaparib is being investigated in clinical trials against prostate cancer, breast cancer and other neoplasms.

Rucaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of advanced mutant BRCA ovarian cancer. Rucaparib is being investigated in clinical trials against prostate cancer, breast cancer and other neoplasms.

Prinomastat is a synthetic hydroxamic acid derivative with potential antineoplastic activity. Prinomastat inhibits matrix metalloproteinases (MMPs) (specifically, MMP-2, 9, 13, and 14), thereby inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis. As a lipophilic agent, prinomastat crosses the blood-brain barrier. Pfizer conducted multicenter, randomized, double-bind, placebo-controlled trials to evaluate the safety and efficacy of prinomastat in combination with standard chemotherapy in patients with advanced hormone refractory prostate cancer and non-small cell lung cancer. However, this study has been terminated for the reason that Prinomastat did not improve the outcome of chemotherapy in non-small cell Lung cancer patients.

The dihydrochloride salt of nolatrexed, a water-soluble lipophilic quinazoline folate analog with antineoplastic activity. Nolatrexed occupies the folate binding site of thymidylate synthase, resulting in inhibition of thymidylate synthase activity and thymine nucleotide synthesis with subsequent inhibition of DNA replication, DNA damage, S-phase cell cycle arrest, and caspase-dependent apoptosis. This agent also exhibits radiosensitizing activity. Orphan designation of nolatrexed was granted in the Unites States of America for treatment of hepatocellular carcinoma.