Echinomycin is a cyclic peptide of the family of quinoxaline antibiotics that was originally isolated from Streptomyces echinatus. It is thought to act as a bifunctional DNA intercalator. Echinomycin has a binding site size of four base pairs. The strong binding sites for echinomycin contain the central two-base-pair sequence 5'-CG-3'. Echinomycin interferes with HIF-1 DNA binding in a sequence-specific fashion. It was brought into clinical trials by the NCI 20 years ago based on its antitumor activity. It has been extensively tested in phase I-II clinical trials. Nausea, vomiting, reversible liver enzyme abnormalities, and allergic reactions were the most common toxicities encountered. However, minimal or no antitumor activity was found in phase II clinical trials.

CUDC-305, is a novel heat shock protein 90 (HSP90) inhibitor with strong affinity for HSP90 alpha/beta, high oral bioavailability and potent anti-proliferative activity against a broad range of cancer cell lines (with a mean IC50 of 220 nmol/L), including many non-small cell lung cancer (NSCLC) cell lines which are resistant to standard-of-care (SOC) agents. In both laboratory and animal testing, CUDC-305 demonstrated high potency in vitro and/or in vivo across a wide range of cancers. Most notably, Curis scientists observed complete tumor regression following oral administration of CUDC-305 in a mouse xenograft model of acute myelogenous leukemia (AML). Tumor regression has also been observed after treatment of CUDC-305 in mouse xenograft models of breast, non-small cell lung, gastric cancer and glioblastoma brain cancers. In this preclinical testing, the compound also demonstrated an ability to effectively cross the blood brain barrier, and demonstrated an ability to extend survival in an intracranial glioblastoma model. Early stage toxicity studies suggest that CUDC-305 appears to have a better therapeutic window than several leading Hsp90 inhibitors in clinical development.

TAK-960 is a novel, investigational, orally bioavailable, potent, and selective PLK1 inhibitor(IC50=1.5 nM) that has shown activity in several tumor cell lines, including those that express multidrug-resistant protein 1 (MDR1). In animal models, oral administration of TAK-960 increased pHH3 in a dose-dependent manner and significantly inhibited the growth of HT-29 colorectal cancer xenografts. Treatment with once daily TAK-960 exhibited significant efficacy against multiple tumor xenografts, including an adriamycin/paclitaxel-resistant xenograft model and a disseminated leukemia model. TAK-960 had been in phase I clinical trials by Takeda for the treatment of solid tumours. It had also been in preclinical trials for the treatment of acute myeloid leukaemia. However, these studies were discontinued.

SGX523 is a selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase. SGX523 was able to inhibit HGF-induced cell migration and cell scatter. SGX523 inhibition of MET in vivo was associated with the dose-dependent inhibition of growth of tumor xenografts derived from human glioblastoma and lung and gastric cancers. The clinical development of SGX523, however, was discontinued at Phase I due to renal toxicity manifested by an early rise of serum blood urea nitrogen and creatinine.

EW-7197 is an orally bioavailable inhibitor of the serine/threonine kinase, transforming growth factor (TGF)-beta receptor type 1 (TGFBR1), also known as activin receptor-like kinase 5 (ALK5), with potential antineoplastic activity. EW-7197 is in phase I clinical trials for the treatment of solid tumors. Also, EW-7197 has a strong potential as an anti-fibrosis therapeutic agent.

E-6005 is a novel PDE4 inhibitor developed as a topical agent for atopic dermatitis (AD). It potently and selectively inhibited human PDE4 activity and suppressed the production of various cytokines from human lymphocytes and monocytes. In mice models, the topical application of E6005 produced an immediate antipruritic effect as well as an anti-inflammatory effect with reduced expression of cytokines/adhesion molecules. E-6005 increases the cutaneous concentration of cAMP to relieve dermatitis-associated itching. E-6005 may be a promising novel therapeutic agent with antipruritic activity for the treatment of AD. E-6005 is currently in phase 2 development for patients with mild-to-moderate atopic dermatitis.

Solcitinib (also known as GSK2586184 or GLPG0778) is a selective Janus kinase 1 (JAK1) inhibitor, for the treatment of psoriasis, lupus, and ulcerative colitis. Galapagos NV's collaboration with GlaxoSmithKline has hit a roadblock. It was reported that its Big Pharma partner had hit the brakes on a Phase II study of GSK2586184 for lupus after a first look at the data failed to demonstrate a positive effect. And an exploratory Phase I/II of the same drug for ulcerative colitis was put on hold as investigators review the program.

Novartis Oncology (previously Novartis) is developing WNT-974 (formerly LGK 974), a first-in-class selective small molecule inhibitor of O-acyltransferase. WNT-974 is under development for the treatment of cancers that are driven by the Wnt pathway in a Wnt ligand-dependent manner. Upon oral administration, WNT-974 binds to and inhibits PORCN in the endoplasmic reticulum (ER), which blocks post-translational acylation of Wnt ligands and inhibits their secretion. This prevents the activation of Wnt ligands, interferes with Wnt-mediated signaling, and inhibits cell growth in Wnt-driven tumors. Porcupine, a membrane-bound O-acyltransferase (MBOAT), is required for the palmitoylation of Wnt ligands, and plays a key role in Wnt ligand secretion and activity. Wnt signaling is dysregulated in a variety of cancers

Icaritin is a monoprenylated favonol with 4′-methoxyl from Epimedium Genus. It has been documented to have osteoblastic and neuroprotective activities. It can reduce the incidence of steroid-associated oesteonecrosis in rabbit with inhibition of both intravascular thrombosis and extravascular lipid deposition for maintaining the integrity of intraosseous vasculature. Icaritin shows anti-infammatory activity and inhibitory activities against cancer cells. The phase III clinical trial is planned for the treatment of Hepatocellular carcinoma.