U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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Showing 121 - 130 of 2746 results

Status:
Investigational
Source:
NCT03189914: Phase 1/Phase 2 Interventional Completed Metastatic Pancreatic Cancer
(2017)
Source URL:

Class (Stereo):
CHEMICAL (ABSOLUTE)


Conditions:

Fluorocyclopentenylcytosine (RX-3117) is a novel small molecule nucleoside compound that is incorporated into DNA or RNA of cancer cells and inhibits both DNA and RNA synthesis which induces apoptotic cell death of tumor cells. Fluorocyclopentenylcytosine also mediates the down-regulation of DNA methyltransferase 1 (DNMT1), an enzyme responsible for the methylation of cytosine residues on newly synthesized DNA and also a target for anticancer therapies. Preclinical studies have shown Fluorocyclopentenylcytosine to be effective in both inhibiting the growth of various human cancer xenograft models, including colon, lung, renal and pancreas, as well as overcoming chemotherapeutic drug resistance. Fluorocyclopentenylcytosine has demonstrated a broad spectrum anti-tumor activity against 50 different human cancer cell lines and efficacy in 12 different mouse xenograft models. The efficacy in the mouse xenograft models was superior to that of gemcitabine. In addition, in human cancer cell lines made resistant to the anti-tumor effects of gemcitabine, Fluorocyclopentenylcytosine still retains its full anti-tumor activity. In August 2012, Rexahn reported the completion of an exploratory Phase I clinical trial of Fluorocyclopentenylcytosine in cancer patients conducted in Europe, to investigate the oral bioavailability, safety and tolerability of the compound. In this study, oral administration of Fluorocyclopentenylcytosine demonstrated an oral bioavailability of 34-58% and a plasma half-life (T1/2) of 14 hours. In addition, Fluorocyclopentenylcytosine was safe and well tolerated in all subjects throughout the dose range tested. Fluorocyclopentenylcytosine is in phase I/II clinical trials by Rexahn for the treatment of bladder cancer and pancreatic cancer. This compound was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pancreatic cancer in September 2014.
Status:
Investigational
Source:
NCT02471846: Phase 1 Interventional Completed Solid Tumor
(2015)
Source URL:

Class (Stereo):
CHEMICAL (ABSOLUTE)


Conditions:

NLG919 is a novel small-molecule IDO-pathway inhibitor. NLG919 potently inhibits this pathway in vitro and in cell-based assays. It is orally bioavailable and has a favorable pharmacokinetic and toxicity profile. In mice, a single oral administration of NLG919 reduces the concentration of plasma and tissue Kyn by ∼ 50%. Using IDO-expressing human monocyte-derived DCs in allogeneic MLR reactions, NLG919 potently blocked IDO-induced T cell suppression and restored robust T cell responses with an ED50=80 nM. Similarly, using IDO-expressing mouse DCs from tumor-draining lymph nodes, NLG919 abrogated IDO-induced suppression of antigen-specific T cells (OT-I) in vitro. In vivo, in mice bearing large established B16F10 tumors, administration of NLG919 markedly enhanced the anti-tumor responses of naïve, resting pmel-1 cells to vaccination with cognate hgp100 peptide plus CpG-1826 in IFA
Status:
Investigational
Source:
NCT01060475: Phase 1 Interventional Completed Healthy
(2010)
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)

Status:
Investigational
Source:
NCT01226407: Phase 1 Interventional Unknown status Solid Tumour
(2010)
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)

CG-200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed by CrystalGenomics, Inc for treatment of various hematological and solid cancers. Combinations of CG-200745 with SN38 (the active form of irinotecan), or oxaliplatin were more effective than the agents alone when used to inhibit the growth of HCT116 cells. The protein expressions of acetyl-H3, p21, caspase-3, -8, and -9, PARP, and XIAP were affected in a time- and dose-dependent manner in HCT116 cells treated with the CG-200745 alone or combined CG-200745 and SN-38. In HCT116 xenografts, the HDACI CG-200745 in combination with irinotecan dramatically inhibited tumor growth without showing additive toxicity.
Status:
Investigational
Source:
NCT03742037: Phase 2 Interventional Completed Systemic Lupus Erythematosus
(2018)
Source URL:

Class (Stereo):
CHEMICAL (ABSOLUTE)


Cenerimod is an orally available sphingosine-1-phosphate receptor 1 (S1P1) modulator that is being developed by Idorsia Pharmaceuticals for the treatment of systemic lupus erythematosus. Sphingosine-1-phosphate (S1P), a lipid mediator, regulates lymphocyte migration between lymphoid tissue and blood. Cenerimod is a potent, selective, safe and orally administrable S1P1 receptor modulator, which reportedly reduced blood lymphocytes and attenuated murine experimental autoimmune encephalomyelitis (EAE) in a murine model. Cenerimod has potential as novel therapy with an improved safety profile for autoimmune diseases with a high unmet medical need.
Status:
Investigational
Source:
NCT03622112: Phase 2 Interventional Completed Asthma
(2019)
Source URL:

Class (Stereo):
CHEMICAL (ABSOLUTE)

Status:
Investigational
Source:
NCT03387215: Phase 1/Phase 2 Interventional Completed Heart Failure, Systolic
(2018)
Source URL:

Class (Stereo):
CHEMICAL (ABSOLUTE)


Status:
Investigational
Source:
NCT02898779: Phase 1 Interventional Completed Malaria
(2017)
Source URL:

Class (Stereo):
CHEMICAL (ABSOLUTE)

Status:
Investigational
Source:
NCT02898779: Phase 1 Interventional Completed Malaria
(2017)
Source URL:

Class (Stereo):
CHEMICAL (ABSOLUTE)

Status:
Investigational
Source:
NCT00903383: Phase 2 Interventional Completed Rheumatoid Arthritis
(2009)
Source URL:

Class (Stereo):
CHEMICAL (ABSOLUTE)

LX 2931 (LX 3305) is an inhibitor of sphingosine 1-phosphate (S1P) lyase. S1P lyase is an enzyme identified as a promising new target on a pathway associated with regulation of the immune system. Lexicon Pharmaceuticals, Inc. was developing LX 2931 for the treatment of rheumatoid arthritis. LX 2931 has disappeared from the pipeline of Lexicon Pharmaceuticals, Inc. In preclinical studies LX 2931 was effective against experimental cerebral malaria, lung inflammation in a F508del CFTR murine cystic fibrosis model and osteoporosis.