Navoximod (formerly NLG 919, GDC 0919), a small molecule, orally bioavailable, immune checkpoint inhibitor, is being developed by NewLink Genetics for the treatment of solid tumours. Navoximod is a potent IDO (indoleamine-(2,3)-dioxygenase) pathway inhibitor with Ki/EC50 of 7 nM/75 nM. Upon administration, navoximod targets and binds to IDO1, a cytosolic enzyme responsible for the oxidation of the essential amino acid tryptophan into kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, this agent increases tryptophan levels, restores the proliferation and activation of various immune cells, including dendritic cells (DCs), natural killer (NK) cells, and T-lymphocytes, and causes a reduction in tumor-associated regulatory T-cells (Tregs). Activation of the immune system, which is suppressed in many cancers, may induce a cytotoxic T-lymphocyte (CTL) response against the IDO1-expressing tumor cells. IDO1 is overexpressed by a variety of tumor cell types and plays an important role in immunosuppression. Tryptophan depletion is associated with immunosuppression caused by T-cell suppression. Navoximod is under investigation in clinical trial NCT02048709 (Indoleamine 2,3-Dioxygenase (IDO) inhibitor in advanced solid tumors).

Levdobutamine is a beta-adrenoceptor agonist selective for the beta1-subtype. Levdobutamine was derived from dopamine. It is the active (S)-isomer of dobutamine. It is the cardiotonic agent.

Triciribine is a purine analogue which inhibits DNA and protein synthesis, it is a synthetic tricyclic nucleoside which acts as a specific inhibitor of the Akt signaling pathway. It selectively inhibits the phosphorylation and activation of Akt1, -2 and -3 but does not inhibit Akt kinase activity nor known upstream Akt activators such as PI 3-Kinase and PDK1. It inhibits cell growth and induces apoptosis preferentially in cells that express aberrant Akt1. In whole cells triciribine is phosphorylated by adenosine kinase which may be necessary for its activity. Triciribine is a cancer drug which was first synthesised in the 1970s and trialled clinically in the 1980s and 1990s without success. Following the discovery in the early 2000s that the drug would be effective against tumours with hyperactivated Akt, it is now again under consideration in a variety of cancers. As PTX-200, the drug is currently in two early stage clinical trials in breast cancer and ovarian cancer being conducted by the small molecule drug development company Prescient Therapeutics.

Mannose 6-phosphate (M6P) has type-I integral membrane receptors. M6P-receptors bind and transport M6P-enzymes to lysosomes, but it can also modulate the activity of a variety of extracellular M6P-glycoproteins (i.e., latent TGFbeta precursor, urokinase-type plasminogen activator receptor, Granzyme B, growth factors, Herpes virus). M6P has been demonstrated to reduce active TGF-β1 expression on cultured tendon fibroblasts and improved range of movement in a rabbit flexor tendon injury model. Studies of M6P in relation to skin scarring demonstrate improvement in scar cosmesis and accelerated return of normal dermal architecture. Juvidex, a formulation of M6P, inhibits the activation of TGF-beta1 and TGF-beta2, which are present at high levels in adult wounds that scar. On the other hands, M6P in a 600 mM hypertonic solution (Adaprev) potentially acts via a physical, non-chemical, hyperosmotic effect.

Oxi0-4503 (now known as combretastatin A1 phosphate), a diphosphate prodrug of combretastatin A1, was developed by Mateon therapeutics as a second-generation, dual-mechanism vascular disrupting agent from the combretastatin family. On November 21, 2012, Oxi-4503 has been granted orphan designation by the US Food and Drug Administration for the treatment of acute myelogenous leukemia. It is known that the orphan drug designation qualifies a company for several benefits, including the potential for market exclusivity, development grants, and tax credits. Oxi0-4503 is currently participating in phase I/II clinical trial the treatment of patients with acute myelogenous leukemia or myelodysplastic syndrome. In addition, phase I clinical trial was successfully completed where was studied the safety of Oxi0-4503 in patients with advanced solid tumors.