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Restrict the search for
m sacubitril
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Status:
Investigational
Class (Stereo):
CHEMICAL (ACHIRAL)
Targets:
Conditions:
Tozasertib, originally developed as VX-680 by Vertex (Cambridge, MA) and later renamed MK-0457 by Merck (Whitehouse Station, NY), was the first aurora kinase inhibitor to be tested in clinical trials. The drug, a pyrimidine derivative, has affinity for all aurora family members at nanomolar concentrations with inhibitory constant values (Ki(app)) of 0.6, 18, and 4.6 nM for aurora A, aurora B, and aurora C, respectively. Preclinical studies confirmed that tozasertib inhibited both aurora A and aurora B kinase activity, and activity has been reported against prostate, thyroid, ovarian, and oral squamous cancer cell lines. Upon treatment with tozasertib, cells accumulate with a 4N DNA content due to a failure of cytokinesis. This ultimately leads to apoptosis, preferentially in cells with a compromised p53 function. Tozasertib is an anticancer chemotherapeutic pan-aurora kinase (AurK) inhibitor that also inhibits FMS-like tyrosine kinase 3 (FLT3) and Abl. Tozasertib is currently in clinical trials as a potential treatment for acute lymphoblastic leukemia (ALL). In cellular models of cancer, tozasertib activates caspase-3 and PARP and decreases expression of HDAC, increasing apoptosis and inhibiting cell growth. In other cellular models, tozasertib inhibits cell proliferation and metastasis by blocking downstream ERK signaling and downregulating cdc25c and cyclin B. This compound also decreases tumor growth in an in vivo model of prostate cancer.
Status:
Investigational
Class (Stereo):
CHEMICAL (ACHIRAL)
Emitefur or BOF-A2 is a fluorinated pyrimidine antimetabolite exerting antineoplastic properties. It is a compound composed of 5-fluorouracil (5-FU) and 3-cyano-2,6-dihydroxypyridine (CNDP), an inhibitor of 5-FU degradation by dihydrouracil dehydrogenase in order to prolong the blood 5-FU level as well as increase selective toxicity to a tumor. Emitefur demonstrated clinical activity in preliminary studies in Japan. Emitefur development for the treatment of solid tumors has been discontinued.
Status:
Investigational
Source:
INN:succinobucol [INN]
Source URL:
Class (Stereo):
CHEMICAL (ACHIRAL)
Succinobucol (also known as AGI-1067) is a probucol derivative patented by American pharmaceutical company Atherogenics, Inc as vascular protectant with antioxidant, anti-inflammatory and antiplatelet activities. In vitro, succinobucol inhibits the TNF-α induced expression of VCAM-1 and MCP-1 with little effect on intercellular adhesion molecule (ICAM)-1. In addition, succinobucol inhibits lipopolysaccharide (LPS)-induced expression of tissue factor in human monocytic cells and endothelial cells, an effect thought to be mediated independently from the nuclear factor κB pathway. Preclinical studies have shown reduced total cholesterol and low-density lipoprotein cholesterol concentrations, increased high-density lipoprotein cholesterol concentrations, decreased levels of inflammatory mediators, and reduced atheroma area with Succinobucol treatment in animal models. Unfortunately, in clinical trials, Succinobucol failed to demonstrate a strong cardioprotective effect. Undesired metabolic effects including high-density lipoprotein cholesterol-lowering have been consistently reported, and diarrhea appears to be an expected adverse effect.
Status:
Investigational
Class (Stereo):
CHEMICAL (ACHIRAL)
Camobucol is a novel, orally active, phenolic antioxidant and anti-inflammatory compound with antirheumatic properties. Camobucol exhibited potent antioxidant activity toward lipid peroxides in vitro and displayed enhanced cellular uptake relative to a structurally related drug, probucol. This resulted in potent inhibition of cellular levels of reactive oxygen species in multiple cell types. Camobucol selectively inhibited tumor necrosis factor (TNF)-alpha-inducible levels of the redox-sensitive genes, vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1, with less inhibition of E-selectin, and no effect on intracellular adhesion molecule-1 expression in endothelial cells. In addition, Camobucol inhibited cytokine-induced levels of monocyte chemoattractant protein-1, interleukin (IL)-6, and IL-8 from endothelial cells and human fibroblast-like synoviocytes as well as lipopolysaccharide-induced release of TNF-alpha, IL-1beta, and IL-6 from human peripheral blood mononuclear cells. Camobucol did not inhibit TNF-alpha-induced nuclear translocation of nuclear factor of the kappa-enhancer in B cells (NF-kappaB), suggesting that the mechanism of action is independent of this redox-sensitive transcription factor.
Status:
Investigational
Source:
INN:naronapride [INN]
Source URL:
Class (Stereo):
CHEMICAL (ABSOLUTE)
Naronapride (ATI-7505), an orally administered, cisapride analogue and serotonin4 (5HT4) receptor agonist, is being developed by Renexxion for the treatment of multiple gastrointestinal disorders. Sinovant is initially developing naronapride for the treatment of irritable bowel syndrome – constipation (IBS-C), a disease that affects millions of Chinese patients and for which few effective treatment options are available. Naronapride has been evaluated in over 900 subjects in multiple randomized controlled clinical studies and has demonstrated promising results in patients with gastroesophageal reflux disease (GERD), erosive esophagitis (EE), and chronic idiopathic constipation (CIC). Naronapride’s low systemic absorption and high specificity for 5HT4 and D2 receptors is thought to improve its safety and tolerability profile relative to other members of the class.
Status:
Investigational
Class (Stereo):
CHEMICAL (ACHIRAL)
Targets:
Conditions:
Elinafide (LU 79553) is a bisintercalating naphthalamide and a topoisomerase II inhibitor has demonstrated a higher binding affinity for DNA and significant antitumour efficacy against a panel of established tumour cell lines, including several multidrug resistant-positive sublines. Elinafide had been in phase II clinical trial for the treatment of ovarian cancer and phase I trials for the treatment of various solid tumours. The major haematological toxicities observed were anaemia and neutropenia. The major non-haematological toxicities observed in the 3-weekly schedule were neuro-muscular presenting clinically as a mixed syndrome of severe weakness (sometimes with pain in both legs), myalgia and arthralgia, asthenia/fatigue/malaise. One fatality was considered related to LU 79553, as the patient had fever and neutropenia. Clinical study of this drug candidate was discontinued due to its neuromuscular dose-limiting toxicity.
Status:
Investigational
Class (Stereo):
CHEMICAL (ABSOLUTE)
Livoletide (AZP-531) is an analog of unacylated ghrelin, a naturally occurring hormone that is thought to counteract the effects of acylated ghrelin. The drug was designed to improve glycaemic control and reduce weight. Livoletide participated in pivotal phase 2b/3 clinical study for the treatment of Prader-Willi syndrome. In addition, the drug was studied in patients with type 2 diabetes mellitus (T2D). Its pharmacokinetic profile, suitable for once daily dosing, and metabolic effects support further clinical development for T2D.
Status:
Investigational
Class (Stereo):
CHEMICAL (ABSOLUTE)
Targets:
Cemadotin (LU103793) is a cytotoxic water-soluble pentapeptide analogue of dolastatin 15. The dolastatin peptides were originally isolated from the shell-less mollusc Dolabella auricularia. Cemadotin blocks cells at mitosis. It exerts its antitumor activity by suppressing spindle microtubule dynamics through a distinct molecular mechanism by binding at a novel site in tubulin. Cemadotin was in phase II clinical trials as a promising cancer chemotherapeutic agent. However, this agent appears to be inactive in the treatment of advanced non-small-cell lung cancer and other tumors and this research has been discontinued.
Status:
Investigational
Class (Stereo):
CHEMICAL (ABSOLUTE)
Targets:
Conditions:
(-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine ((-)-3-PPP, also known as preclamol) has a dual action towards to dopamine D2 autoreceptor: it activates it and also acts concomitantly as an antagonist at postsynaptic DA receptors. It was shown, that (-)-3PPP/preclamol was a safe drug for study in the treatment of schizophrenia and may have antipsychotic efficacy. Besides, the motor effects of the drug were evaluated in nine patients with Parkinson's disease using a double-blind, placebo-controlled design. However, the small number of patients manifesting a clinically significant response and the frequently inconsistent effects could indicate that this class of agents may have relatively limited clinical utility.
Class (Stereo):
CHEMICAL (ABSOLUTE)
As a narcotic antagonist similar in action to naloxone, DIPRENORPHINE is used to remobilize animals after analgesia by super-potent opioid analgesics such as etorphine and carfentanil. It is not used in humans. Diprenorphine binds approximately equally to the three subtypes of opioid receptors (mu, delta, and kappa) and antagonizes them. This compound belongs to the class of organic compounds known as phenanthrenes and derivatives. These are polycyclic compounds containing a phenanthrene moiety, which is a tricyclic aromatic compound with three non-linearly fused benzene. The therapeutic efficacy of many other compounds can be decreased when used in combination with Diprenorphine (54 compounds mentioned on www.drugbank.ca).
