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.

Cucurbitacin I (JSI-124) is a novel selective triterpenoid that acts as a potent inhibitor of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway with anti-proliferative and anti-tumor properties. Cucurbitacin I specifically suppresses levels of tyrosine phosphorylated STAT3 in v-Src-transformed NIH 3T3 cells and in A549 cells (IC50 = 500 nM) resulting in inhibition of STAT3 DNA binding and reduced STAT3-mediated gene transcription. It also suppresses JAK2 phosphorylation but does not affect Src, ERK, JNK or Akt. In nude mice, cucurbitacin I (1 mg/kg/day) suppressed the growth of various tumors expressing constitutively active STAT3.1 It promotes the differentiation of dendritic cells and macrophages and enhances the effect of cancer immunotherapy. Cucurbitacin I (1 µM for 2 hours) reduced clonogenicity of nasopharyngeal carcinoma cells in vitro and suppresses tumor growth in mice (1.3 mg/kg).

CVT-6883 (GS 6201) is an A2B adenosine receptor antagonist originated by CV Therapeutics and developed by Gilead Sciences or the treatment of pulmonary diseases. In vitro studies have suggested that the activation of the A2B adenosine receptor may potentially have Proinflammatory and profibrotic effects that could be significant in the development of lung diseases. In adenosine deaminase (ADA) deficient mice, treatment with GS 6201 resulted in significantly less pulmonary inflammation, fibrosis, and alveolar airway enlargement compared with ADA-deficient mice treated with placebo. A range of doses of GS 6201 was well tolerated in healthy volunteers in a phase I multiple ascending dose trial.

RO-20-1724 is a potent inhibitor of Phosphodiesterase 4 (PDE4) originally developed by Roche. It showed some promise as a potential treatment for psoriasis, but it was discontinued when it could not match the efficacy of existing treatments. RO-20-1724 was also investigated as a potential treatment for asthma and septic shock.

JTC 801 was developed by Japan Tobacco as a novel opioid receptor-like1 (ORL(1)) receptor antagonist. It was found, that JTC-801 completely antagonized the suppression of nociceptin on the forskolin-induced accumulation of cyclic AMP using ORL(1) receptor expressing HeLa cells in vitro. JTC 801 produced analgesic effects and was studied in phase II of a clinical trial for the treatment of neuropathic, cancer and postoperative pain. Nevertheless, that studies were discontinued.