Track topics on Twitter Track topics that are important to you
This letter describes the discovery of a novel series of tetrahydroisoquinoline (THIQ)-derived small molecules that potently inhibit both human T-cell migration and super-antigen induced T-cell activation through disruption of the binding of integrin LFA-1 to its receptor, ICAM-1. In addition to excellent in vitro potency, 6q shows good pharmacokinetic properties and its ethyl ester (6t) demonstrates good oral bioavailability in both mouse and rat. Either intravenous administration of 6q or oral administration of its ethyl ester (6t) produced a significant reduction of neutrophil migration in a thioglycollate-induced murine peritonitis model.
Sunesis Pharmaceuticals, Inc., 395 Oyster Point Blvd., Suite 400, South San Francisco, CA 94080, USA.
This article was published in the following journal.
Name: Bioorganic & medicinal chemistry letters
The p97 AAA-ATPase plays vital roles in mechanisms of protein homeostasis, including ubiquitin-proteasome system (UPS) mediated protein degradation, endoplasmic reticulum-associated degradation (ERAD)...
Tetrahydroisoquinoline-derived urea and 2,5-diketopiperazine derivatives as selective antagonists of the transient receptor potential melastatin 8 (TRPM8) channel receptor and anti-prostate cancer agents.
Tetrahydroisoquinoline derivatives containing embedded urea functions were identified as selective TRPM8 channel receptor antagonists. Structure activity relationships were investigated, with the foll...
Based on a crystal structure of a phenylpyrrolidine lead and subsequent molecular modeling results, we designed and synthesized a novel series of macrocyclic FVIIa inhibitors. The optimal 16-membered ...
The structure-based design of 1, 2, 3, 4-tetrahydroisoquinoline derivatives as selective DDR1 inhibitors is reported. One of the representative compounds, 6j, binds to DDR1 with a Kd value of 4.7 nM a...
A series of novel hedgehog signaling pathway inhibitors have been designed by structural modification based on the former reported scaffold of 4-(2-pyrimidinylamino)benzamide. The SAR for this series ...
IPI-493 is a potent inhibitor of heat shock protein 90 (Hsp90) and is orally bioavailable via a novel formulation.
ISIS 2302 is an antisense oligonucleotide drug that reduces the production of a specific protein called intercellular adhesion molecule (ICAM-1), a substance that plays a significant role ...
The purpose of this prospective clinical trial is to document the performance and clinical outcomes of Biomet Discovery Elbow.
Non-small cell lung cancer (NSCLC) is the most common cause of cancer mortality in men and women in Singapore.Chemotherapy and biologically targeted agents can extend survival only modestl...
Risedronate is an orally administered pyridinyl bisphosphonate that is 36 times more potent than pamidronate and 72 times more potent than clodronate. Four randomized, double-blind trials...
A long-acting beta-2-adrenergic receptor agonist. It is a potent bronchodilator that may be administered orally or by aerosol inhalation.
Morphine derivatives of the methanobenzazocine family that act as potent analgesics.
A toxic compound, isolated from the Spanish fly or blistering beetle (Lytta (Cantharis) vesicatoria) and other insects. It is a potent and specific inhibitor of protein phosphatases 1 (PP1) and 2A (PP2A). This compound can produce severe skin inflammation, and is extremely toxic if ingested orally.
Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.
A plant family of the order Cornales, subclass Rosidae, class Magnoliopsida, consisting of slow-growing evergreen trees common in tropical forests of south India and Burma. Members contain tetrahydroisoquinoline-monoterpene and iridoid glycosides.
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...