BMS 599626 is a selective and efficacious inhibitor of HER1 and HER2 with IC50 of 20 nM and 30 nM. BMS-599626 is identified as an ATP-competitive inhibitor for HER1 and as an ATP-noncompetitive inhibitor for HER2. BMS-599626 inhibits the proliferation of tumor cells expressing high levels of HER1 and/or HER2, including Sal2, BT474, N87, KPL-4, HCC202, HCC1954, HCC1419, AU565, ZR-75-30, MDA-MB-175, GEO, and PC9 cells. In a phase I trial of solid tumour patients receiving BMS 599626 no doselimiting toxicities were observed during the first cycle. Grade 1 or 2 drugrelated effects were reported and included diarrhoea, nausea, vomiting, rash, fatigue, musculoskeletal pain/cramp and cough. BristolMyers Squibb discontinued development of BMS 599626 for cancer in July 2015

Sanguinarine is an extract of the bloodroot plant Sanguinaria canadensis, a member of the poppy family. It is an inhibitor of protein phosphatases PP1, PP2C and PP2B in vitro. Also inhibits mitogen-activated protein kinase phosphatase-1 (MKP-1) and other enzymes. Sanguinarine exerts a protective effect in cerebral ischemia, and this effect is associated with its anti-inflammatory and anti-apoptotic properties. It was clinically tested as an agent against gingivitis and tooth plaques.

Mertansine (Maytansine) is a 19–member ansa macrolide structure attached to a chlorinated benzenering. It was originally isolated from the shrub Maytenus ovatus. Mertansine (DM1) is a tubulin inhibitor, it inhibits the assembly of microtubules by binding to tubulin, with a linker structure can create an antibody-drug conjugate (ADC). Mertansine is a potent microtubule-targeted compound that induces mitotic arrest and kills tumor cells at sub-nanomolar concentrations. The antimitotic effect of maytansine has been attributed to its ability to inhibit microtubule assembly by binding to tubulin with a KD of ~ 1 umol/L, at or near the vinblastine-binding site. Experimental ADCs with the SPP-DM1 design include lorvotuzumab mertansine. DM1 can also be linked to an antibody using the SMCC (4-(3-mercapto-2,5-dioxo-1-pyrrolidinylmethyl)-cylohexanecarboxylic acid) linker, in which case the International Nonproprietary Name of the conjugate formed contains the word emtansine. DM1 and its attachment via these linkers result from ImmunoGen Inc research. Trastuzumab emtansine (T-DM1) is an anti-HER2/neu antibody-drug conjugate.

The compound StemRegenin 1 (SR1) is a selective, cell-permeable, small molecule that promotes the self-renewal of human hematopoietic stem cells in culture. SR1 is an antagonist of the aryl hydrocarbon receptor. SR1 is the first small molecule that promotes robust expansion/self-renewal of human CD34 peripheral blood and cord blood hematopoietic stem cells (HSCs). The culture of HSCs with SR1 led to a 50-fold increase in cells expressing CD34 and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. SR1 can be potentially used for ex vivo expansion of normal HSCs or leukemic stem/progenitor cells

HMR 1031 is a potent and specific antagonist of the integrin VLA-4 (alpha4beta1) binding to vascular cell adhesion molecule-1 (VCAM-1) and fibronectin. HMR 1031 is an inhaled drug being developed for the treatment of asthma using an Ultrahaler dry-powder inhalation device. The interaction of VLA-4 with VCAM-1 is involved in the extravasations, activation, and extravascular survival of mononuclear leukocyte and eosinophil cell types at sites of airway inflammation. Thus, the VLA-4 antagonist, HMR 1031, has potential as an anti-inflammatory agent.

AZ-1080 (AZD-1080) is an inhibitor of GSK-beta which was developed by AstraZeneca and initially tested in patients with Alzheimer’s disease (phase I). The drug was discontinued for the aforementioned condition, but now it is being investigated as a potential therapy for ovarina cancer and emdometrial carcinoma (basic research).

Cinobufagin is a bufadienolide compound extracted from the dried venom secreted by the parotid glands of toads and one of the glycosides in the traditional Chinese medicine ChanSu, with potential antineoplastic activity. Cinobufagin has been shown to have clinical applications in cancer treatment as well as immunomodulatory and analgesic properties. Cinobufagin induces apoptosis of osteosarcoma cells through inactivation of Notch signaling. Cinobufagin induces autophagy-mediated cell death in human osteosarcoma U2OS cells through the ROS/JNK/p38 signaling pathway. Cinobufagin significantly relieved cancer pain in mice and raised their pain threshold, mainly upregulating the expression levels of beta-Endorphin and μ- opioid receptor in the hind paw tumor and adjacent tissue. In combination with gemcitabine-oxaliplatin cinobufagin was used in clinical trial for the treatment of locally advanced or metastatic gallbladder carcinoma.

GSK1070916 is a novel, azaindole derived, reversible and ATP-competitive inhibitor of the Aurora B/C kinases. GSK1070916 inhibits the proliferation of tumor cells and has antitumor effects in 10 human tumor xenograft models including breast, colon, lung, and two leukemia models. Nemucore Medical Innovations and Cancer Research UK are developing NMI 900 (previously GSK 1070916) for the intravenous treatment of cancer. The product was originally developed by GlaxoSmithKline. A phase I/II trial in patients with solid tumours has been completed in the UK. Phase II development in ovarian cancer is underway in the US.

INCB3284 or INCB-3284 Incyte’s internally developed, oral human CCR2 antagonist for the treatment of chronic inflammations. It is in Phase IIa trial of patients with rheumatoid arthritis (RA).

Levovirin is a guanosine nucleoside analog and the L-enantiomer of ribavirin. It is an investigational drug for the treatment of hepatitis C virus-mediated diseases. Levovirin has a similar immunomodulatory potency to ribavirin in vitro without accumulating in red blood cells or causing hemolytic anemia, a known side effect of ribavirin. Levovirin has been shown to stimulate host immune responses (enhanced Th1 and reduced Th2 cytokine expression). Significantly improved oral absorption of levovirin was achieved following administration of a valine ester prodrug of levovirin R1518. Levovirin was found more potent to inhibit Tick-borne encephalitis virus (TBEV) on the basis of robust binding affinity between protein-drug interactions. This finding may help to understand the nature of helicase and development of specific anti-TBEV therapies.