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.

Galeterone (TOK-001, formerly called VN/124-1) is a potent anti-androgen with three modes of action. The compound acts as a specific androgen receptor antagonist, inhibits CYP17 lyase while conserving CYP17 hydroxylase function, and decreases overall androgen receptor levels in prostate cancer cells. Galeterone is a first in class, multi-targeted small-molecule drug that disrupts the growth and survival of prostate cancer cells. Tokai Pharmaceuticals is developing galeterone as an oral treatment for castration-resistant prostate cancer. Phase III clinical development of galeterone is underway in the US, Canada, Australia, Western Europe, Spain and the United Kingdom.

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.

Esoxybutynin is (S)-enantiomer of oxybutynin. Esoxybutynin exerts antimuscarinic properties. Racemic oxybutynin is used clinically to treat urinary incontinence. Sepracor was developing (S)-oxybutynin, a single-isomer version of Alza's Ditropan (racemic oxybutynin), a muscarinic acetylcholine receptor antagonist, as a potential treatment for urinary incontinence.

LADARIXIN is a dual inhibitor of chemokine receptors CXCR1 and CXCR2. It inhibits human polymorphonuclear leukocyte (PMN) migration to chemokine CXCL8 in vitro and prevents PMN infiltration and tissue damage in several models of cerebral ischemia/reperfusion in vivo. It is under development for the treatment of type 1 diabetes.

AZD-1981, developed by AstraZeneca, is a potent (binding IC50 of 4nM), fully reversible, functionally non-competitive antagonist of human CRTh2. It blocks agonist-induced human eosinophil CD11b expression, shape change (including in whole blood), and chemotaxis as well as an basophil shape change and Th2-cell chemotaxis at IC50's of 8.5-50nM. Potency is similar across species as is plasma protein binding (~97%). AZD-1981 is a weak (10s of μM) inhibitor in vitro of CYP2C9, OATP1B1 and UGT1A1 as well as an inducer of CYP3A4. AZD-1981 was well tolerated and no safety concerns were identified.There was no beneficial clinical effect of AZD-1981, at a dose of 1000 mg twice daily for 4 weeks, in patients with moderate to severe COPD. AZD-1981 has being discontinued for asthma and chronic obstructive pulmonary disease. AstraZeneca is collaborating with Johns Hopkins University for the development of AZD-1981 in the treatment of chronic idiopathic urticaria. It is in phase II clinicals studies for the treatment of Urticaria.

Danixirin is a potent, competitive, selective and reversible antagonist of the chemokine receptor (CXCR2) (also known as interleukin 8B receptor). In preclinical models, danixirin blocked neutrophils chemotaxis in response to inflammation. The drug is being developed by GlaxoSmithKline for the treatment of chronic obstructive pulmonary disease, influenza, respiratory syncytial virus. In phase 2 clinical trials in patients with acute, uncomplicated influenza, danixirin was well tolerated and did not impede viral clearance.

MPEP (2-methyl-6-(phenylethynyl)pyridine) was one of the first compounds found to act a selective antagonist for the metabotropic glutamate receptor subtype mGluR5. It was under development by Novartis in the late 1990's. MPEP was found to produce neuroprotective effects following acute brain injury in animals. MPEP was also found to have positive effects on animal models of depression, anxiety and morphine withdrawl.