CC-220 is a potent cereblon modulating agent that displays anti-proliferative, pro-apoptotic and immunomodulatory activity on sensitive and resistant multiple myeloma cell lines. CC-220 is currently under clinical investigation for systemic lupus erythematosus and multiple myeloma as a single agent, or in combination with dexamethasone in patients who may have previously been exposed to pomalidomide. Comparable to other Cereblon-binding agents, ex vivo treatment of CC-220 on B-cells, T-cells, and monocytes leads to the degradation of the hematopoietic transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). followed by disruption of the multiple myeloma promoting c-Myc/IRF4 axis.

Ipatasertib (LCL161) binds to inhibitors of apoptosis proteins (IAPs) with high affinity and initiates the destruction of cIAP1 and cIAP2, which further induces apoptosis via caspase activation. Ipatasertib is advancing in clinical development including five Phase 2 trials in patients with Breast cancer, Multiple myeloma, Myelofibrosis, Small cell lung cancer and Ovarian cancer. The most common LCL161-related adverse events were nausea and vomiting.

Oprozomib (PR-047) is an orally bioavailable derivative of carfilzomib, with similar biological activity, i.e. inhibition of the chymotrypsin-like activity of the proteasome. It inhibits the activity of the proteasome, thereby blocking the targeted proteolysis normally performed by the proteasome; this may result in an accumulation of unwanted or misfolded proteins. Disruption of various cell signaling pathways may follow, eventually leading to the induction of apoptosis and inhibition of tumor growth. Oprozomib (PR-047) is being investigated for the treatment of hematologic malignancies, specifically, multiple myeloma, with Phase I/II trial ongoing.

NM404 I-131 (also known as CLR 131) is a phospholipid ether analog labeled with iodine I-131, used as radiotherapeutic and positron emission tomography (PET) radioimaging agent. Upon infusion, the drug accumulates in tumor cells and is retained for a long time because of the decreased activity of a phospholipase D. The drug is being developed by Cellectar Biosciences and is investigated in clinical trials against multiple myeloma and hematologic malignancies. In 2014, the FDA granted orphan drug designation for CLR 131 for the treatment of multiple myeloma.

HDAC-IN-2 (also known as citarinostat or ACY-241) was developed as a selective histone deacetylase (HDAC) 6 inhibitor with potential antineoplastic activity. Inhibition of HDAC leads to the inhibition of tumor oncogene transcription, and the selective transcription of tumor suppressor genes, which inhibit tumor cell division and induce tumor cell apoptosis. HDAC-IN-2 participates in phase 1b clinical trial in patients with multiple myeloma to determine the maximum tolerated dose (MTD) and evaluate the safety and preliminary antitumor activity. Besides, HDAC-IN-2 in combination with paclitaxel participates in phase Ib in patients with advanced solid tumors. In addition, HDAC-IN-2 in combination with nivolumab participates in phase I in patients with unresectable non-small cell lung cancer to determine the safety, tolerability, dose-limiting toxicities (DLTs), and maximum tolerated dose (MTD) of the drug.

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.

Alethine (Beta alethine) is an immunostimulant agent. It was undergoing clinical development with LifeTime Pharmaceuticals for the treatment of haematological malignancies. It is a low molecular weight disulfide that has been shown to exhibit in vivo antitumor activity in murine myeloma and melanoma models.

Imexon (INN, trade name Amplimexon) is a substance that is being studied in the treatment of some types of cancer, including pancreatic, lung, breast, prostate, melanoma, and multiple myeloma. Imexon is a thiol-binding small molecule which induces mitochondrial oxidation, a loss of membrane potential and cytochrome C, leading to apoptosis.

Tasquinimod is a drug, developed by Active Biotech Research and tested in phase III of clinical trials for the treatment of Castrate Resistant Prostate Cancer. The drug acts by targeting the tumor microenvironment with S100A9 being one of molecular targets.