BX 471 is an oral nonpeptide chemokine receptor1 (CCR1) antagonist that was under clinical development with Bayer Healthcare Pharmaceuticals (formerly Bayer Schering Pharma AG and Berlex) for the treatment of various inflammation-related disorders, including endometriosis. The CCR1 antagonist was also thought to have potential application in diagnostic imaging, particularly as an imaging biomarker for the diagnosis of Alzheimer's disease. Berlex initiated the development of the radiolabelled small molecule CCR1 antagonist, BX 471, for a specific diagnostic test for both early detection and for tracking disease progression following the discovery that the CCR1 protein was found in the brains of patients with Alzheimer's disease, and that increased levels of this protein were correlated with advancement of the disease. However, development of the agent for diagnostic imaging appears to have been discontinued. BX 471 was also in development for the treatment of autoimmune diseases, including multiple sclerosis and psoriasis; however, development in these indications, as well as multiple myeloma and endometriosis, also appears to have been discontinued. A phase II study of BX 471 in endometriosis had been completed.

Ilorasertib (previously known as ABT-348), an orally bioavailable ATP-competitive inhibitor of Aurora kinases (A, B and C), as well as the VEGF and PDGF families of receptor tyrosine kinases, was developed by AbbVie as an antineoplastic agent. It is known that Aurora kinases A, B, and C play essential roles in mitotic checkpoint control and are overexpressed by a wide variety of tumor cell types. Both VEGFRs and PDGFRs may be upregulated in various tumor cell types. Ilorasertib alone or in combination with azacitidine demonstrated activity in preclinical models in various hematological malignancies, indicating that pan-Aurora kinase and multiple kinase inhibition may have preferential antileukemic activity. Ilorasertib participated in phase I clinical for patients with advanced hematologic malignancies. The result has shown that the drug could be further studied in acute myelogenous leukemia. Ilorasertib is also going to be studied in phase II clinical trials to learn if this drug can help to control CDKN2A-deficient cancer in patients with advanced cancers.

AZD4818 was developed by AstraZeneca as CCR1 receptor antagonist for the treatment of patients with chronic obstructive pulmonary disease. The study was discontinued, because of a lack of clinical efficacy.

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.

Fedovapagon, also known as VA106483 and VT483, is a potent, nonpeptidic vasopressin V2 receptor agonist. Vasopressin (AVP) is a hormone that stimulates an increase in water permeability through activation of V2 receptors in the kidney. Fedovapagon (VA106483) was discovered by Vantia and currently in Phase II trials for the treatment of nocturia, a common condition that causes sufferers to wake frequently during the night in order to urinate. Fedovapagon has been extensively studied in clinical trials and data, presented at the American Urological Association meeting in 2010, demonstrated a dose-dependent reduction in nocturnal urine volumes and a reliable pharmacodynamic effect on repeated dosing. More recently, data presented in San Diego at the 2012 American Urological Association meeting, showed that fedovapagon was effective from the first night of dosing and that there was no effect following cessation of dosing. Further presentations are planned for the International Continence Society meeting being held in Barcelona in August 2013. These data suggest that fedovapagon has the potential to be an effective and well tolerated antidiuretic for the treatment of nocturia. Fedovapagon is currently being investigated as a new treatment for nocturia in a Phase-II/III clinical trials in USA (PO)(NCT02637960).

CAT-1004 (Edasalonexent)is an orally administered small molecule designed to inhibit NF-κB, which is activated from infancy in Duchenne muscular dystrophy and is central to causing muscle damage and preventing muscle regeneration. Structurally CAT-1004 represents covalently links salicylic acid and docosahexaenoic acid -- two compounds known to inhibit NF-κB. . In a Phase 1 study in adults, NF-κB activity in peripheral mononuclear cells was inhibited following a single dose of edasalonexent but not by equimolar doses of salicylic acid and docosahexaenoic acid. Chronic activation of NF-κB is a key driver of muscle degeneration and suppression of muscle regeneration in Duchenne muscular dystrophy, which occurs early in the disease process and precedes loss of muscle function. Salicylic acid prevents NF-κB mediated muscle atrophy and decreases protein catabolism in muscle. Docosahexaenoic acid has been shown to upregulate anti-inflammatory pathways and suppress pro-inflammatory pathways via modulation of NF-κB activity. Edasalonexent is endocytosed and hydrolyzed by intracellular fatty acid amide hydrolase (FAAH) to release salicylic acid and DHA in the intracellular compartment, thus having a potential advantage of selectively delivering higher doses in target muscle cells where FAAH is abundant.

Flosfluridine tidoxil, a thymidylate synthase inhibitor that was developed for the treatment of actinic keratosis and solid tumors, e.g. breast and colorectal cancers. These studies were suspended and information about the further development of this drug is not available.

AZD5672 was developed by AstraZeneca for the treatment of rheumatoid arthritis. It was found that the drug inhibits P-glycoprotein and is a CCR5 antagonist. Exists hypothesis that inhibition of CCR5 can bring benefits in the treatment of rheumatoid arthritis. In July 2009, Phase-II for Rheumatoid arthritis was discontinued.

Burixafor is an orally bioavailable inhibitor of CXC chemokine receptor 4 (CXCR4) with receptor binding and hematopoietic stem cell-mobilization activities. Burixafor binds to the chemokine receptor CXCR4, thereby preventing the binding of stromal derived factor-1 (SDF-1 or CXCL12) to the CXCR4 receptor and subsequent receptor activation; this may induce the mobilization of hematopoietic stem and progenitor cells from the bone marrow into the blood. CXC motif chemokine receptor 4 (CXCR4) blockade is pursued as an alternative to mesenchymal stem cell treatment after heart transplantation. The augmentation of conventional mycophenolate mofetil plus corticosteroids with a CXCR4 antagonist is potentially effective in improving outcomes after heart transplantation in humans