CF102 known as Cl-IB-MECA (2-chloro-N6-(3-iodobenzyl)-adenosine-5’- N-methyl-uronamide), is a highly specific and selective agonist at the A3 adenosine receptor. Phase I/II study in hepatocellular carcinoma (HCC) successfully met its primary and secondary endpoints demonstrating initial indications for efficacy of CF102. A global Phase II study treating patients with CF102 as a second line therapy will start enroling patients shortly.

SQ-109 is a [1,2]-diamine-based ethambutol (EMB) analog developed for the treatment of tuberculosis. SQ109 acts by inhibiting MmpL3, a transporter of trehalose monomyclate, which is an important component of cellular wall. The drug was investigated as a monotherapy or in combination with rifampicin in phase II clinical trials in pulmonary tuberculosis patients. The clinical trials, however, did not demonstrate activity of SQ-109 alone or its ability to enhance the activity of rifampicin.

Dinaciclib (SCH 727965) is a small molecule inhibitor of cyclin-dependent kinases. Dinaciclib demostrates potent and selective inhibition of CDK2, CDK5, CDK1, and CDK9 activity. Dinaciclib inhibits cell cycle progression and proliferation in various tumor cell lines in vitro. Dinaciclib is a product of a drug discovery collaboration between Pharmacopeia (later Ligand Pharmaceuticals) and Schering-Plough (later Merck & Co.) that began in 1998. Dinaciclib showed promising effect in treating haematological malignancies and solid tumors.

Volasertib (BI 6727), a dihydropteridinone derivative, is a small-molecule cell cycle inhibitor of polo-like kinase-1 (PLK-1). Volasertib induces G2-M arrest and induction of apoptosis in cancer cells and potently inhibits tumor growth in xenograft models. Boehringer Ingelheim is developing intravenously administered volasertib for the treatment of acute myeloid leukaemia (AML), myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML), non-small cell lung cancer, urogenital cancer, ovarian cancer and solid tumours.

Pracinostat is a pan-histone deacetylase inhibitor being tested in phase II of clinical trials for the treatment of sarcoma, prostate cancer, acute myeloid leukemia, myelofibrosis, myelodysplastic syndrome. The drug was shown to be active in vitro on HCT116 and HL-60 cells.

Anatibant was a selective small-molecule antagonist of the bradykinin B2 receptor that was undergoing clinical development with Xytis and Fournier for the treatment of brain injuries. Anatibant reduces brain oedema in animal TBI models. Noserious toxicity was found in Phase 1 clinical trials. Following subcutaneous administration of clinically relevant doses, there were no systemic effects but there was pain, inflammation and nodule formation at the injection site. Anatibant inhibits the binding of BK to the B2 receptor. After subcutaneous injection Anatibant is bio-available and crosses the BBB.

Veliparib (ABT-888) is a potent inhibitor of PARP, has good oral bioavailability, can cross the blood-brain barrier, and potentiates temozolomide, platinums, cyclophosphamide, and radiation in syngeneic and xenograft tumor models. AbbVie is developing veliparib for the treatment of cancers. Clinical trials are underway worldwide, investigating veliparib primarily as part of a combination therapy in oncology indications such as brain, colorectal, melanoma, ovarian, prostate and pancreatic cancers.

Talarozole (formerly R115866) is a new highly potent and selective azole derivative, which inhibits cytochrome-P450-dependent all-trans-retinoic acid catabolism by blocking the cytochrome P450 enzyme isoform CYP26, a retinoic acid hydroxylase. It is in clinical development for the treatment of psoriasis and acne. However, no local pharmacokinetic data on the diffusion behaviour of talarozole in the skin itself are available. As topical application might be an interesting alternative to oral therapy because of the reduced systemic side effects. The distribution of talarozole within the skin was investigated: 80% was located in the epidermis, while the remaining 20% was found in the dermis. The epidermal concentration of talarozole achieved after a single topical application was sufficiently high to enable the potential induction of local retinoid-like effects.