2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU) is an alkylating chloroethylnitrosourea with antineoplastic activity. It is a selective cytotoxin that enters cells via the extraneuronal transporter for monoamine transmitters (EMT). Both in vitro and in vivo studies demonstrated that SarCNU was more effective than BCNU against human gliomas. Selectively accumulating in some tumor cells, SarCNU forms covalent linkages with nucleophilic centers in DNA, causing depurination, base pair miscoding, strand scission, and DNA-DNA cross-linking, which may result in cytotoxicity. SarCNU crosses the blood-brain-tumour-barrier and is taken orally. Phase II trial of SarCNU in malignant glioma revealed unexpected pulmonary toxicity. SarCNU was not FDA approved for orphan indication of malignant glioma.

ABT-751 is an orally bioavailable antimitotic sulfonamide, which binds to the colchicine-binding site on beta-tubulin and inhibits the polymerization of microtubules, leads to a block in the cell cycle at the G2M phase, resulting in cellular apoptosis. ABT-751 had been in phase Ⅱ clinical studies for the treatment of breast cancer; colorectal cancer; non-small cell lung cancer; renal cancer, prostate cancer, but these researches have been discontinued.

Deferitrin is a desferrithiocin-derived hexadentate iron chelator, developed by Genzyme Corp. for the treatment of severe iron overload in people who require repeated erythrocyte transfusion for the management of chronic anemia such as beta-thalassemia major. Development of the drug was halted after phase 1/2 clinical trial due to nephrotoxicity.

RO-638695 (also known as Miridesap, CPHPC and GSK-2315698) is an antineoplastic and a serum amyloid P component inhibitor. RO-638695 almost completely depletes circulating serum amyloid P component (SAP), but a small amount of SAP is left for recognition by subsequently administered therapeutic IgG anti-SAP antibodies. SAP is a blood protein that is the target of a novel immunotherapy approach. RO-638695 has therefore been evaluated in phase I and II clinical trials for its safety and potential in treatment of diseases like Alzheimer’s disease, HIV infection and other diseases with systemic amyloid deposition.

Zamicastat (also known as BIA 5-1058) is a dopamine β-hydroxylase (DβH) inhibitor that decreases noradrenaline and increases dopamine levels in peripheral sympathetically innervated tissues. It is known that the use of DβH inhibitors is a promising approach to treat hypertension, heart failure and cardiovascular diseases where a reduction in the sympathetic tone has beneficial effects. Zamicastat participated in phase II clinical trials in pulmonary arterial hypertension as adjuvant therapy in Austria. In addition, the drug successfully completed phase I in patients with hypertension and chronic heart failure.

24-Hydroxycalcidiol (24,25-dihydroxy vitamin D3) is a circulating metabolite of vitamin D3. 24,25(OH)2D3 functions by activation of Vitamin D receprtor and promotion of ostecalcin expression, but is less effective than other D3 metabolite, 1alpha,25(OH)2D3. There is conflicting evidence on efffect of 24-hydroxycalcidiol on bone metabolism. In several animal studies it was demonstrated that 24-hydroxycalcidiol was able to stimulate calcification of bone and restore the reduction in bone mineral apposition rate. However, no beneficial effect of 24R,25(OH)2D3 treatment of postmenapausal women on bone mineral density or bone loss and calcium metabolism were observed.