Nutlins are cis-imidazoline analogs which inhibit the interaction between mdm2 and tumour suppressor p53. Inhibiting the interaction between mdm2 and p53 stabilizes p53, and is thought to selectively induce a growth-inhibiting state called senescence in cancer cells. These compounds are therefore thought to work best on tumors that contain normal or "wild-type" p53. Nutlin-3 does not induce the phosphorylation of p53 on key serine residues and reveals no difference in their sequence-specific DNA binding and ability to transactivate p53 target genes compared with phosphorylated p53 induced by the genotoxic drugs doxorubicin and etoposide, demonstrating that phosphorylation of p53 on key serines is dispensable for transcriptional activation and apoptosis.

Basmisanil (INN) (developmental code names RG-1662, RO5186582) is a highly selective inverse agonist/negative allosteric modulator of α5 subunit-containing GABAA receptors which is under development by Roche for the treatment of cognitive impairment associated with Down syndrome. The phase II trials were recently terminated due to lack of efficacy. This outcome suggests either that the α5-NAM was insufficiently effective to restore neuronal plasticity or alternatively that the hypothesis of excessive GABAergic inhibition obstructing neuronal plasticity does not extend to individuals with DS.

RO-5045337 (RG7112) is a small molecule that binds to a MDM2, a negative regulator of tumor-supressor protein p53. It was discovered by Roche and investigated in clinical trials against solid tumors, leukemias and sarcomas.

Bitopertin is a Glycine transporter type 1 inhibitor which was developed by Hoffmann-La Roche for the treatment of patients with schizophrenia. The drug was shown to be potent in vitro, however it failed to meet primary endpoints in phase III. Bitopertin was also tested for the treatment of obsessive-compulsive disorder, but the development stopped in phase II.

Diclofensine is an antidepressant with equipotent inhibitive effects on the neuronal uptake of norepinephrine (NE), serotonin, and dopamine. It is devoid of monoamine-releasing or monoaminoxidase-inhibiting properties. Diclofensine was found to be an effective antidepressant in human trials, with relatively few side effects, but was ultimately dropped from clinical development.

Racemethorphan is racemic mixture of Dextromethorphan and Levomethorphan. Racemethorphan is listed under the Single Convention on Narcotic Drugs 1961 and is therefore listed in the United States as a Controlled Substance, specifically as a Narcotic in Schedule II. Dextromethorphan is a non-narcotic morphine derivative widely used as an antitussive. Dextromethorphan is a cough suppressant in many over-the-counter cold and cough medicines. In 2010, the FDA approved the combination product dextromethorphan/quinidine for the treatment of pseudobulbar affect. Dextromethorphan suppresses the cough reflex by a direct action on the cough center in the medulla of the brain. Levomethorphan is an opioid analgesic of the morphinan family that has never been marketed.

5-Fluoro-2-deoxycytidine is a fluorinated pyrimidine analog antimetabolite with potential antineoplastic activity. As a prodrug, 5-fluoro-2-deoxycytidine is converted by intracellular deaminases to the cytotoxic agent 5-fluorouracil (5-FU). 5-FU is subsequently metabolized to active metabolites including 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP binds to and inhibits thymidylate synthase, thereby reducing the production of thymidine monophosphate, which leads to depletion of thymidine triphosphate and the inhibition of DNA synthesis and cell division. FUTP competes with uridine triphosphate (UTP) for incorporation into the RNA strand, which results in the inhibition of RNA and protein synthesis and cell proliferation. 5-Fluoro-2-deoxycytidine undergoing trials to test its effectiveness in treating cancer that has not responded to standard therapies.

Iomazenil (also known as Ro16-0154, benzodine) is a partial inverse agonist of central-type benzodiazepine receptors (BZR) which binds specifically to BZR with high affinity and a potential treatment for alcohol abuse. The compound was introduced in 1989 by pharmaceutical company Hoffmann-La Roche as an Iodine-123-labelled SPECT tracer for imaging benzodiazepine receptors (GABAA receptors) in the brain.

R1530 is the multikinase inhibitor with potential antiangiogenesis and antineoplastic activities. R1530 is also a mitosis-angiogenesis inhibitor (MAI) that inhibits multiple receptor tyrosine kinases involved in angiogenesis, such as vascular endothelial growth factor receptor (VEGFR)-1, -2, -3, platelet-derived growth factor receptor (PDGFR) beta, FMS-like tyrosine kinase (Flt)-3, and fibroblast growth factor receptor (FGFR) -1, -2. In addition, this agent exhibits anti-proliferative activity by initiating mitotic arrest and inducing apoptosis. In the presence of R1530, polyploid cancer cells underwent apoptosis or became senescent which translated into potent in vitro and in vivo efficacy. Normal proliferating cells were resistant to R1530-induced polyploidy thus supporting the rationale for cancer therapy by induced polyploidy. Mitotic checkpoint kinase BubR1 was found downregulated during R1530-induced exit from mitosis, a likely consequence of PLK4 inhibition. R1530 strongly inhibited human tumor cell proliferation and growth factor-driven proliferation of endothelial and fibroblast cells. Significant tumor growth inhibition was demonstrated in a lung cancer xenograft model with a range of once daily, weekly and twice-weekly doses of R1530. Daily doses were most effective in the lung cancer model and also had significant growth inhibitory effects in models of colorectal, prostate, and breast tumors. Tumor regression occurred in all models treated with the maximum tolerated daily dose. The doses of 25 and 50 mg/kg QD resulted in biologically significant increased survival in all tested models. After oral administration in nude mice, R1530 showed good tissue penetration. R1530 had been in phase I clinical trials by Hoffmann-La Roche, Inc. for the treatment of advanced solid tumors. However, the clinical development of R1530 was discontinued.

Cinalukast (Ro 24-5913 ) is a selective leukotriene D4 receptor antagonist originated by Roche. Cinalukast inhibits the actions of Leukotriene D4 at the cysteinyl leukotriene receptor, CysLT1, in the human airway. Leukotriene receptor occupation has been correlated with the pathophysiology of asthma, including airway edema and altered cellular activity associated with the inflammatory process, which contributes to the signs and symptoms of asthma. Cinalukast had been investigated for the treatment of asthma, but that study was discontinued.