JNJ-7925476
JNJ-7925476 is a TRI antidepressant currently under development by Johnson & Johnson.
These molecules were first prepared by Bruce E. Maryanoff, et al. during the late 1970s – 1980's. and is known as a pyrroloisoquinoline, that is benzhydryl-containing.
Incorporating the pyrrolidino ring onto the THIQ scaffolding markedly improves potency, although this only works for one of the available diastereo/enantiomers. JNJ-7925476 is a racemic preparation of the more potent diastereomer. The eutomer, JNJ-39836966 has (6R,10bS)-stereochemistry whereas the distomer JNJ-39836732 will have (6S,10bR)-stereochemistry.
The compounds depicted appear to be cis but Maryanoff and coworkers are of the opinion that it is trans. (see abstract)
The reason for this is not known because it was referred to as "cis" to begin with, only reassigning it later.
In-vitro characterization
Ki values (nM) for JNJ-7925476 and its constituent enantiomers (JNJ-39836966 and JNJ-39836732)
In vitro, JNJ-7925476 is ~18-fold selective for the hSERT (0.9 nM) over the hNET (16.6 nM).
JNJ-7777120
JNJ-7777120 is a drug being developed by Johnson & Johnson Pharmaceutical Research & Development which acts as a potent and selective antagonist at the histamine H4 receptor. It has anti-inflammatory effects, and has been demonstrated to be superior to traditional antihistamines in the treatment of pruritus (itching).
See also
References
Canagliflozin
Canagliflozin (INN, trade name Invokana or Sulisent) is a drug of the gliflozin class, used for the treatment of type 2 diabetes. It was developed by Mitsubishi Tanabe Pharma and is marketed under license by Janssen, a division of Johnson & Johnson.
Medical use
Canagliflozin is an antidiabetic drug used to improve glycemic control in people with type 2 diabetes. In extensive clinical trials, canagliflozin produced a consistent dose-dependent reduction in HbA1c of 0.77% to 1.16% when administered as monotherapy, combination with metformin, combination with metformin and a sulfonylurea, combination with metformin and pioglitazone, and in combination with insulin from a baselines of 7.8% to 8.1%, in combination with metformin, or in combination with metformin and a sulfonylurea. When added to metformin, canagliflozin 100 mg was shown to be non-inferior to both sitagliptin 100 mg and glimepiride in reductions on HbA1c at one year, whilst canagliflozin 300 mg successfully demonstrated statistical superiority over both sitagliptin and glimiperide in HbA1c reductions. Secondary efficacy endpoint of superior body weight reduction and blood pressure reduction (versus sitagliptin and glimiperide)) were observed as well. Canagliflozin produces beneficial effects on HDL cholesterol whilst increasing LDL cholesterol to produce no change in total cholesterol.
JNJ-42165279
JNJ-42165279 is a drug developed by Johnson & Johnson which acts as a potent and selective inhibitor of the enzyme fatty acid amide hydrolase (FAAH), with an IC50 of 70nM. It is described as a covalently binding but slowly reversible selective inhibitor of FAAH. JNJ-42165279 is being developed for the treatment of anxiety and major depressive disorder. Clinical development has progressed as far as Phase II human trials with two studies in patients with mood disorders registered in ClinicalTrials.gov.
Following a series of severe adverse events, including a death, in a trial with a different FAAH inhibitor BIA 10-2474, Janssen announced that it was temporarily suspending dosing in its two Phase II clinical trials with JNJ-42165279, headlining the decision as "precautionary measure follows safety issue with different drug in class". Janssen was emphatic that no serious adverse events had been reported in any of the clinical trials with JNJ-42165279 to date. The suspension is to remain in effect until more information is available about the BIA 10-2474 study.
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