BCX-4430 hydrochloride is a salt of an antiviral adenosine analog BCX4430 (Immucillin-A) that acts as a viral RNA-dependent RNA polymerase (RdRp) inhibitor. It was developed as a potential treatment for deadly filovirus infections such as Ebola virus disease and Marburg virus disease but also demonstrated broad-spectrum antiviral effectiveness against a range of other RNA virus families, including, bunyaviruses, arenaviruses, paramyxoviruses, and coronaviruses. Biochemical, reporter-based and primer-extension assays indicate that BCX4430 inhibits viral RNA polymerase function, acting as a non-obligate RNA chain terminator. BCX4430 inhibits infection of distinct filoviruses in human cells. Post-exposure administration of BCX4430 protects rodents against Ebola and Marburg virus disease and cynomolgus macaques from Marburg virus when administered as late as 48 hours after infection. BCX4430 is highly active in a Syrian golden hamster model of yellow fever, even when treatment is initiated at the peak of viral replication. BCX4430 also showed efficacy against Zika virus in a mouse model.

PF-04217903 is a triazolopyrazine inhibitor of c-MET that displays anticancer chemotherapeutic and anti-metastatic activities. PF-04217903 inhibits cell proliferation, invasion, and migration as well as tumor growth in various cancer models. In animal models of pancreatic neuroendocrine tumors, this compound prevents lymph node metastasis. PF-04217903 had been in phase I clinical trials by Pfizer for the treatment of solid tumors. In 2011, the company discontinued the development of the compound.

Amgen is developing AMG-900, an orally active, small molecule aurora kinase A, B and C inhibitor for the treatment of solid tumours and haematological malignancies. In tumor cells, AMG-900 inhibited autophosphorylation of aurora-A and -B as well as phosphorylation of histone H3 on Ser(10), a proximal substrate of aurora-B. The predominant cellular response of tumor cells to AMG-900 treatment was aborted cell division without a prolonged mitotic arrest, which ultimately resulted in cell death. AMG-900 inhibited the proliferation of 26 tumor cell lines, including cell lines resistant to the antimitotic drug paclitaxel and to other aurora kinase inhibitors (AZD1152, MK-0457, and PHA-739358), at low nanomolar concentrations. Furthermore, AMG-900 was active in an AZD1152-resistant HCT116 variant cell line that harbors an aurora-B mutation (W221L). Oral administration of AMG-900 blocked the phosphorylation of histone H3 in a dose-dependent manner and significantly inhibited the growth of HCT116 tumor xenografts. Importantly, AMG-900 was broadly active in multiple xenograft models, including 3 multidrug-resistant xenograft models, representing 5 tumor types. AMG-900 has entered clinical evaluation in adult patients with advanced cancers and has the potential to treat tumors refractory to anticancer drugs such as the taxanes.

Adoprazine (SVL-313) is a full 5-HT1A receptor agonist and full D2/3 receptor antagonist possessing characteristics of an atypical antipsychotic, representing a potential novel treatment for schizophrenia and bipolar disorder. This drug together with some others, e.g. Mazapertine succinate, PF-217830 was discontinued from clinical trials due to either non-optimal pharmacokinetic properties or insufficient therapeutical efficacy.

AGE-RELATED MACULAR DEGENERATION (AMD), PROLIFERATIVE DIABETIC RETINOPATHY (PDR) AND DIABETIC MACULAR EDEMA (DME) are collectively characterized by VEGF mediated retinal leakage, angiogenesis, and an underlying inflammatory process. TargeGen's TG100801 is designed to inhibit a select group of kinases involved in those three processes. Currently approved drug based therapy for macular degeneration requires repeated injection into the eye. TG100801 is the first topically applied, VEGFR)/Src kinase inhibitor to advance into the clinic for the treatment of Age-related macular degeneration, diabetic retinopathy. The formation of new blood vessels (angiogenesis), blood vessel leakage, and inflammation contribute to the progression of the eye disease, which is the leading cause of irreversible, severe loss of vision in people 55 years of age and older in the developed world. In cell based assays, following topical instillation, TG100572, the active drug produced by conversion of TG100801 as it penetrates the eye, was shown to induce apoptosis in proliferating endothelial cells responsible for neovasculariztion and to inhibit inflammatory-mediated processes as measured by endotoxin-induced nitric oxide release in vitro.

Q203 (6-chloro-2-ethyl-N-(4-(4-(4-(trifluoromethoxy)phenyl)piperidin-1-yl)benzyl)imidazo [1,2-a]pyridine-3-carboxamide) is an an imidazopyridine antitubercular compound. Q203 targets the cytochrome b subunit (QcrB) of the cytochrome bc1 complex. This complex is an essential component of the respiratory electron transport chain of ATP synthesis. Q203 inhibited the growth of multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Q203 is a promising new clinical candidate for the treatment of tuberculosis.

Pinometostat, also known as EPZ-5676, is a small molecule inhibitor of histone methyltransferase with potential antineoplastic activity. Upon intravenous administration, EPZ-5676 specifically blocks the activity of the histone lysine-methyltransferase DOT1L, thereby inhibiting the methylation of nucleosomal histone H3 on lysine 79 (H3K79) that is bound to the mixed lineage leukemia (MLL) fusion protein which targets genes and blocks the expression of leukemogenic genes. Epizyme is developing pinometostat, a small molecule inhibitor of DOT1L, for the treatment of patients with MLL-r, a genetically defined acute leukemia. Epizyme is conducting a phase 1 clinical trial in pediatric patients. Epizyme is evaluating preclinical combinations of pinometostat with other anti-cancer agents in MLL-r leukemia. Pinometostat is being developed in collaboration with Celgene. Epizyme retains all U.S. rights to pinometostat and has granted Celgene an exclusive license to pinometostat outside of the U.S.

Cevipabulin is a synthetic, water-soluble tubulin-binding agent with potential antineoplastic activity. Cevipabulin appears to bind at the vinca-binding site on tubulin but seems to act more similar to taxane-site binding agents in that it enhances tubulin polymerization and does not induce tubulin depolymerization. The disruption in microtubule dynamics may eventually inhibit cell division and reduce cellular growth.

Cevipabulin is a synthetic, water-soluble tubulin-binding agent with potential antineoplastic activity. Cevipabulin appears to bind at the vinca-binding site on tubulin but seems to act more similar to taxane-site binding agents in that it enhances tubulin polymerization and does not induce tubulin depolymerization. The disruption in microtubule dynamics may eventually inhibit cell division and reduce cellular growth.

CEP-37440 is a potent ATP-competitive, highly kinase selective, and orally active inhibitor of FAK1 and anaplastic lymphoma kinase (ALK). In addition to a favorable metabolic stability and pharmacokinetic profile preclinically, CEP-37440 is also a brain penetrant. CEP-37440 was able to inhibit the proliferation of certain IBC cells by decreasing the levels of phospho-FAK1 (Tyr 397); none of the cells expressed ALK. Studies using IBC xenograft models showed that CEP-37440 also effectively reduces the growth of the primary tumor xenografts and inhibits the development of brain metastases in mice.