ZIRCONIUM ZR-89 is used in specialized diagnostic applications using positron emission tomography (PET). An increasing interest in zirconium-89 can be attributed to the isotope's half-life, which is compatible with antibody imaging. ZR-89 as a radioimmunoconjugate, [89Zr]DFO-HuMab-5B1 was used in preclinical animal models of lung, colorectal, and pancreatic malignancies for PET imaging and was in a phase I trial for pancreatic cancer. In addition, the use of 89Zr-DFO-nimotuzumab that had low organ absorbed dose and effective dose made it suitable for potential human use for immunoPET imaging of epidermal growth factor receptor I. It is known, that epidermal growth factor receptor upregulation is associated with enhanced proliferation and drug resistance in a number of cancers.

Q203 (6-chloro-2-ethyl-N-(4-(4-(4-(trifluoromethoxy)phenyl)piperidin-1-yl)benzyl)imidazo [1,2-a]pyridine-3-carboxamide) is an an imidazopyridine antitubercular compound. Q203 targets the cytochrome b subunit (QcrB) of the cytochrome bc1 complex. This complex is an essential component of the respiratory electron transport chain of ATP synthesis. Q203 inhibited the growth of multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Q203 is a promising new clinical candidate for the treatment of tuberculosis.

Naglivan [PMD 501, vanadeine] is a vanadyl organometallic agent, in the preclinical phase of development in France, with Pan Medica, as an orally-active drug for the treatment of diabetes mellitus. Naglivan is an orally effective form of vanadyl with an oral potency 7.6 times greater than that of vanadyl sulfate (minimum effective dose: 0.06 mmol vanadium.kg-1.day-1) as compared to vanadyl sulfate (0.46 mmol vanadium.kg-1.day-1). The lack of incidence of diarrhea in either control or diabetic animals demonstrates that naglivan could be a more therapeutically desirable form of vanadyl.

GDC-0994 (RG7842) is a selective inhibitor of ERK1/2, also known as extracellular-signal-regulated kinases. Daily, oral dosing of GDC-0994 results in significant single-agent activity in multiple in vivo cancer models, including KRAS-mutant and BRAF-mutant human xenograft tumors in mice. GDC-0994 neither increases nor decreases phospho-ERK, suggesting that different ERK inhibitors have alternative mechanisms of action with respect to feedback signaling. GDC-0994 is currently advancing in a Phase 1 trial in patients with solid tumors.

ME-344 is an isoflavone-derived antineoplastic agent. ME-344 is an active metabolite of NV-128. ME-344 exerts antitumor activity through inhibiting mitochondrial NADH: ubiquinone oxidoreductase (Complex I) and inducing caspase-independent cell death through the Akt/mammalian target of rapamycin pathway. ME-344 inhibited tubulin polymerization by interacting with tubulin near the colchicine-binding site. Furthermore, inhibition of tubulin polymerization was functionally important for ME-344 induced death. ME-344 is being developed for the treatment of solid tumors.

Atuveciclib (previously known as BAY 1143572) was developed as a highly selective inhibitor of positive transcription elongation factor b (PTEFb) /CDK9 for the treatment of cancer. PTEFb is a heterodimer of CDK9 and one of four cyclin partners, cyclin T1, cyclin K, cyclin T2a or cyclin T2b. Atuveciclib also inhibits RNA polymerase II (Ser2) phosphorylation and downregulate MYC protein expression in hematologic malignancies. The drug participated in phase I clinical trials in subjects with advanced acute leukemia and for patients with advanced malignancies. Information about further studies for these types of cancer is not available. Recently published article has shown that atuveciclib enhanced the antineoplastic effects of cisplatin and promoted inhibitory effects on breast cancer stem-like cells grown as mammospheres. In addition, was suggested that CDK9 could be a potential therapeutic target in aggressive forms of CDK9-high triple-negative breast cancer (TNBC).

Vivolux developed VLX-1570 as a small molecule proteasome 19S proteasome deubiquitinase (DUB) inhibitor. In addition, VLX1570 shows selectivity for ubiquitin-specific protease-14 and induces apoptosis of multiple myeloma cells. VLX-1570 participated in phase I/II clinical trial in patients with myeloma. However, this study was terminated because of the dose-limiting toxicity was observed. Thus, the full clinical trial was put on hold. VLX1570 also inhibits ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5). Besides, was shown that VLX1570 modulated bio-cellular pathways that were essential for Waldenstrom macroglobulinemia (WM) cell survival. Thus, VLX1570 can be further studied for clinical use in patients with WM.

Fallypride is a high-affinity antagonist of dopamine D2 and D3 receptors. 18F-radiolabeled fallypride is used as a PET tracer to characterize D2/D3 receptors in the brain.

Ciraparantag (PER-977, aripazine), developed by Perosphere Inc., is a small, synthetic, water-soluble, cationic molecule and can reverse the anticoagulation mediated by unfractionated heparin, low-molecular-weight heparin, factor Xa and factor IIa inhibitors, and fondaparinux. It has the potential to be a universal antidote, inhibiting nearly all anticoagulants except vitamin K antagonists and argatroban. In April 2015, ciraparantag received FDA fast-track designation as an investigational anticoagulant reversal agent. Phase I/II trials are currently underway to evaluate the safety and efficacy of PER977 in reversing anticoagulation of edoxaban, LMWH, and UFH.2.