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.

Oprozomib (PR-047) is an orally bioavailable derivative of carfilzomib, with similar biological activity, i.e. inhibition of the chymotrypsin-like activity of the proteasome. It inhibits the activity of the proteasome, thereby blocking the targeted proteolysis normally performed by the proteasome; this may result in an accumulation of unwanted or misfolded proteins. Disruption of various cell signaling pathways may follow, eventually leading to the induction of apoptosis and inhibition of tumor growth. Oprozomib (PR-047) is being investigated for the treatment of hematologic malignancies, specifically, multiple myeloma, with Phase I/II trial ongoing.

Mafodotin (mc-MMAF) is a hydrophilic non-cleavable antimicrotubule and antimitotic agent, monomethyl auristatin F (MMAF) derivative, having a maleimidocaproyl linker (mc linker), which is ready to conjugate to an antibody or other proteins or biopolymers. Antibody-drug conjugates having mafodotin such as Depatuxizumab mafodotin and Belantamab mafodotin have undergone clinical trials for the treatment of neoplasms.

BMS-986094 (formerly known as INX-189), a nucleotide polymerase (NS5B) inhibitor was developed for the treatment of hepatitis C. Drug participated in phase II clinical trials to evaluate its safety and tolerability. However, in 2012 Bristol-Myers Squibb announced discontinues the development due to safety reasons. The U.S. Food and Drug Administration (FDA) subsequently placed BMS-986094 on clinical hold.