AZD-2461 is an oral inhibitor of PARP-1, which was developed by AstraZeneca as a potential anti-cancer medicine. The drug was tested in phase I clinical patients against solid tumosr, but its development was discontinued.

DC-0623 is an orally active, selective and ATP-uncompetitive MEK inhibitor with potential antineoplastic activity. GDC-0623 specifically inhibits mitogen-activated protein kinase kinase (MEK or MAP/ERK kinase), resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation. In a panel of mutant cancer cell lines, GDC-0623 inhibits cellular proliferation with EC50 values in the low nanomolar range. In vivo, GDC-0623 (40 mg/kg, p.o.) causes potent tumor growth inhibition (TGI) in mouse MiaPaCa-2 (120%), A375 (102%) and HCT116 (115%) xenografts. GDC-0623 had been in phase I clinical trials by Genentech, Inc. for the treatment of Advanced or Metastatic Solid Tumors. However, the clinical development of GDC-0623 was discontinued.

XL-888 is a highly potent and orally bioavailable ATP-competitive inhibitor of HSP90, a molecular chaperone protein that regulates the activity and stability of a range of key regulatory proteins, including a number of kinases implicated in cancer cell growth and survival. In preclinical studies, XL-888 has been shown to inhibit the proliferation of a broad panel of human tumor cell lines, and to induce marked degradation of HSP90 client proteins, including BRAF, MET, and HER2. XL-888 was discovered by Exelixis and is wholly owned by the company. XL-888 is currently in Phase I clinical trials for the treatment of malignant melanoma.

PF-04217903 is a triazolopyrazine inhibitor of c-MET that displays anticancer chemotherapeutic and anti-metastatic activities. PF-04217903 inhibits cell proliferation, invasion, and migration as well as tumor growth in various cancer models. In animal models of pancreatic neuroendocrine tumors, this compound prevents lymph node metastasis. PF-04217903 had been in phase I clinical trials by Pfizer for the treatment of solid tumors. In 2011, the company discontinued the development of the compound.

Pfizer was developing PF-3882845, an orally available nonsteroidal antagonist of the mineralocorticoid receptor, for the treatment of diabetic nephropathies. PF‐03882845 is a highly potent (IC50 = 6.3‐13.4 nM, 10% fetal bovine serum & IC50 = 0.504–1.11 nM, absence of serum) selective orally bioavailable mineralocorticoid receptor antagonist. It is a non‐steroidal pyrazoline, unlike steroidal compounds eplerenone and spironolactone. It does not significantly activate or inhibit human androgen receptor, estrogen receptor alpha, and glucocorticoid receptor. PF‐03882845 has been shown to modestly inhibit the progesterone receptor (PR) yielding a 45‐fold selectivity over PR in a cell‐based functional assay. PF‐03882845 was previously in development for the treatment of diabetic nephropathy — development for this indication was terminated for strategic reasons. An alternative indication of hypertension also was not pursued for strategic reasons.

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.

MK-2048, diketo acid derivative, is a second-generation integrase strand transfer inhibitor (INSTI) developed to retain activity against HIV containing mutations associated with resistance to first-generation INSTIs, raltegravir (RAL) and elvitegravir (EVG). MK-2048 implements its inhibitory mechanism by modifying viral integrase-DNA interactions, the important step of the linear HIV-1 cDNA integration into the host genome. It binds to and inactivates the synaptic complex, an intermediate in the concerted integration pathway in vitro thereby preventing target DNA binding and concerted integration. MK-2048 is active against viruses resistant to RAL and EVG. MK-2048 is equally potent against wild-type IN and raltegravir-resistant IN mutant N155H with a low IC50 value of 42 nM for inhibiting concerted integration. It inhibits R263K mutants slightly more effectively than G118R mutants. MK-2048 exposure leads to the selection of G118R as a possible novel resistance mutation.

PF-04620110 is an orally active, selective and potent DGAT1 (Acyl-CoA:diacylglycerol acyltransferase 1) inhibitor that inhibits triacylglycerol synthesis in cells and in rodents. PF-04620110 inhibits DGAT-1 with an IC50 of 19 nM and shows high selectivity versus a broad panel of off-target pharmacologic end points. In vivo DGAT-1 inhibition has been demonstrated through reduction of plasma triglyceride levels in rodents at doses of ≥0.1 mg/kg following a lipid challenge. On the basis of this pharmacologic and pharmacokinetic profile, PF-04620110 has been advanced to human clinical studies. PF-4620110 had been in phase I clinical trials by Pfizer for the treatment of type 2 diabetes. But this research was discontinued in 2011.

DBPR-108 is a potent, selective, and orally bioavailable dipeptide-derived inhibitor of DPP4 with IC50 of 15 nM; no inhibition on DDP8 and DPP9, which is in phase I clinical trial as a potential treatment of type 2 diabetes.