DOV 216,303 [(+/-)-1-(3, 4-dichlorophenyl)-3-azabicyclo-[3.1.0] hexane hydrochloride] is the prototype of a class of compounds referred to as "triple" reuptake inhibitors. DOV 216,303 were licensed from Wyeth in 1998. This compound inhibits the reuptake of norepinephrine (NE), serotonin (5-HT), and dopamine (DA), the three neurotransmitters most closely linked to major depressive disorder. In August 2004, DOV entered into a development and commercialization partnership for the triple reuptake inhibitors (DOV 21,947 and DOV 216,303) with Merck for depression.

Tosedostat is a proprietary orally bioavailable inhibitor of the M1 family of aminopeptidases with potential antineoplastic activity. Tosedostat is converted intracellularly into a poorly membrane-permeable active metabolite (CHR-79888) which inhibits the M1 family of aminopeptidases, particularly puromycin-sensitive aminopeptidase (PuSA), and leukotriene A4 (LTA4) hydrolase; inhibition of these aminopeptidases in tumor cells may result in amino acid deprivation, inhibition of protein synthesis due to a decrease in the intracellular free amino acid pool, an increase in the level of the proapoptotic protein Noxa, and cell death. There are several ongoing Phase 2 cooperative group-sponsored trials and investigator-sponsored trials evaluating the clinical activity of Tosedostat in combination with standard agents in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

P276-00 (also known as riviciclib) is a novel, potent, small-molecule, flavone-derived inhibitor of cyclin-dependent kinases (Cdk), Cdk 4 D1, Cdk1 B, and Cdk9 T, with potent cytotoxic effects against chemosensitive and chemoresistant cancer cell lines. P276-00 was in phase II clinical trial for the treatment mantle cell lymphoma, but that study was terminated based on interim results and all subjects were off study at that time. Although, there were not the major safety or tolerability concerns. However, this drug successfully passed phase II clinical trial for the treatment Melanoma, squamous cell carcinoma of head and neck, malignant melanoma and in combination with Gemcitabine in the treatment of advanced pancreatic cancer.

DOV 216,303 [(+/-)-1-(3, 4-dichlorophenyl)-3-azabicyclo-[3.1.0] hexane hydrochloride] is the prototype of a class of compounds referred to as "triple" reuptake inhibitors. DOV 216,303 were licensed from Wyeth in 1998. This compound inhibits the reuptake of norepinephrine (NE), serotonin (5-HT), and dopamine (DA), the three neurotransmitters most closely linked to major depressive disorder. In August 2004, DOV entered into a development and commercialization partnership for the triple reuptake inhibitors (DOV 21,947 and DOV 216,303) with Merck for depression.

Zoniporide hydrochloride is a novel, potent and selective NHE-1 inhibitor (IC50 = 14 nM). Reduces infarct size in the isolated heart (EC50 = 0.25 nM). Attenuates post-ischemic cardiac contractile dysfunction and ischemia-reperfusion-induced ventricular fibrillation in vivo. Zoniporide hydrochloride represents a novel class of potent and selective human NHE-1 inhibitors with potential utility for providing cardioprotection in a clinical setting.

Zoniporide hydrochloride is a novel, potent and selective NHE-1 inhibitor (IC50 = 14 nM). Reduces infarct size in the isolated heart (EC50 = 0.25 nM). Attenuates post-ischemic cardiac contractile dysfunction and ischemia-reperfusion-induced ventricular fibrillation in vivo. Zoniporide hydrochloride represents a novel class of potent and selective human NHE-1 inhibitors with potential utility for providing cardioprotection in a clinical setting.

Zoniporide hydrochloride is a novel, potent and selective NHE-1 inhibitor (IC50 = 14 nM). Reduces infarct size in the isolated heart (EC50 = 0.25 nM). Attenuates post-ischemic cardiac contractile dysfunction and ischemia-reperfusion-induced ventricular fibrillation in vivo. Zoniporide hydrochloride represents a novel class of potent and selective human NHE-1 inhibitors with potential utility for providing cardioprotection in a clinical setting.

Zoniporide hydrochloride is a novel, potent and selective NHE-1 inhibitor (IC50 = 14 nM). Reduces infarct size in the isolated heart (EC50 = 0.25 nM). Attenuates post-ischemic cardiac contractile dysfunction and ischemia-reperfusion-induced ventricular fibrillation in vivo. Zoniporide hydrochloride represents a novel class of potent and selective human NHE-1 inhibitors with potential utility for providing cardioprotection in a clinical setting.

Pevonedistat (MLN4924), discovered by Millennium, is a small molecule inhibitor of the NEDD8-Activating Enzyme (NAE), a key component of the protein homeostasis pathway. MLN4924 is a mechanism-based inhibitor of NAE and creates a covalent NEDD8-MLN4924 adduct catalyzed by the enzyme. The NEDD8-MLN4924 adduct resembles NEDD8 adenylate, the first intermediate in the NAE reaction cycle, but cannot be further utilized in subsequent intraenzyme reactions. The stability of the NEDD8-MLN4924 adduct within the NAE active site blocks enzyme activity, thereby accounting for the potent inhibition of the NEDD8 pathway by MLN4924. This drug is in phase II clinical trial for the treatment acute myeloid leukemia, chronic myelomonocytic leukemia and myelodysplastic syndromes. In addition in phase I for treatment acute lymphoblastic leukemia. The ability of MLN4924 to cross the blood-brain barrier, its low toxicity, and clinical efficacy in other cancers suggests that this drug is an attractive treatment against glioblastomas.

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.