GDC-0917 (CUDC-427) is an orally available, monovalent mimetic of the second mitochondrial-derived activator of caspases (Smac/DIABLO) and inhibitor of IAPs (Inhibitor of Apoptosis Proteins) with potential antineoplastic activity. Smac mimetic GDC-0917 binds to the Smac binding groove on IAPs, including the direct caspase inhibitor X chromosome-linked IAP (XIAP) and the cellular IAPs 1 and 2. This inhibits the activities of these IAPs and promotes the induction of apoptosis through apoptotic signaling pathways. GDC-0917 demonstrated single-agent antitumor activity in mouse xenograft models bearing subcutaneous MDA-MB-231 tumors. In addition, CUDC-427 demonstrated additive activity in combination with chemotherapeutic agents and tumor necrosis factor apoptosis-inducing ligand (TRAIL) receptor targeting antibodies in xenograft tumor models. Preclinical safety and pharmacokinetic testing established an expected therapeutic range of doses as well as elucidated possible toxicities including inflammatory cytokine and chemokine proteins that could cause an inflammatory reaction, and reversible mild to moderate inflammation in the lungs and liver. GDC-0917 had been in phase I clinical trials by Genentech, Inc. for the treatment of Refractory Solid Tumors or Lymphoma. The principal toxicities related to CUDC-427 were mild to moderate in severity and included fatigue, nausea, vomiting, and rash.

GDC-0349 is a potent and selective ATP-competitive inhibitor of mTOR. GDC-0349 demonstrates pathway modulation and dose-dependent efficacy in mouse xenograft cancer models.

PF-04691502 is a PI3K/mTOR dual inhibitor. It was tested in phase 2 clinical trials against endometrial cancer and breast cancer, but its development was discontinued due to unacceptable toxicity.

UT-231B is an iminosugar that was under development by United Therapeutics Corporation as an oral drug for the treatment of hepatitis C virus (HCV). UT-231B completed acute and chronic Phase I dosing studies in early 2003. A Phase II proof-of-concept study for UT-231B in patients infected with hepatitis C who have failed conventional therapies was started, but the development of drug seemed to be discontinued.

Elubrixin (SB-656933) is a CXCR2 antagonist that demonstrates dose-dependent effects on neutrophil activation and recruitment. In preclinical studies, the compound was shown to inhibit CXCL1-induced CD11b up-regulation on PMNs in an in vitro whole blood assay and to be active in in vivo rodent inhalation challenge models of airway inflammation that used endotoxin and ozone to induce airway neutrophilia. Elubrixin was being developed by GlaxoSmithKline for the treatment of chronic obstructive pulmonary disease, cystic fibrosis and ulcerative colitis. Elubrixin was withdrawn from the Phase II trial due to the lack of efficacy.

Deleobuvir is a drug for the treatment of Hepatitis C, developed by Boehringer Ingelheim. Deleobuvir is a non-nucleoside HCV NS5B polymerase inhibitor that reversibly and noncovalently binds to the thumb pocket 1. It has shown rapid and strong antiviral activity when administered in combination with peginterferon-a2a and ribavirin. In 2014 Boehringer Ingelheim decided to halt further development of deleobuvir because preliminary analysis of phase 3 clinical trials indicated a low efficacy of the drug.

SRT2104, also known as GSK2245840, is a novel, first in class, highly selective small molecule activator of the NAD + dependent deacetylase SIRT1. SIRT1 has been suggested as putative therapeutic target in multiple age-related diseases including type 2 diabetes and dyslipidemias. SRT2104 in the phase II of clinical trial to treat type 2 diabetes mellitus and psoriasis also in the phase I for its use in case of colitis. Also was reported, that we report that SRT2104, penetrated the blood-brain barrier, attenuated brain atrophy, improved motor function, and extended survival in a mouse model of Huntington's disease.