Delving into the Latest Updates on Wyeth-Ayerst Research with Synapse

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Respiratory Diseases

Immune System Diseases

Cardiovascular Diseases

Small molecule drug

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Immune System Diseases	4
Infectious Diseases	1
Neoplasms	1

Top 5 Drug Type	Count

Small molecule drug	11

Top 5 Target	Count

CysLT1(Cysteinyl leukotriene receptor 1)	5
AVPR1A x AVPR2	1
SERT(Serotonin transporter)	1
Na/K-ATPase(Sodium/potassium-transporting ATPase)	1
ADRA1(Adrenergic receptor alpha-1)	1

SUMMARYThe effect of the immunosuppressive agent rapamycin (RAPA) was assessed in the non-obese diabetic (NOD) mouse which is an autoimmune model of IDDM. RAPA was prepared in a vehicle of 8% cremophor EL/2% ethanol and investigated in two studies. NOD/MrK female mice (six per group, study no. 1; 10 per group, study no. 2) were dosed three times per week p.o. by gavage from 56 to 170 days of age (study no. 1) or from 64 to 176 days or age (study no. 2). Mice treated with RAPA at 06 mg/kg, 6 mg/kg, or 12 mg/kg maintained normal plasma glucose through 170 or 176 days of age with 10%, 0%, and 0% incidence of diabetes respectively. In contrast, naive, vehicle-treated, or RAPA 0.06 mg/kg-treated mice exhibited elevated plasma glucose and disease incidence typical for female NOD mice. Mice which became diabetic had elevated levels of β-hydroxybutyrate, triglycerides and cholesterol. These plasma lipid concentrations were positively correlated with the duration of hyperglycaemia (r= 0.85, 0.87 and 0.84 respectively). Outside of its ability to prevent diabetes, RAPA itself did not affect the lipid profile of the mice. Intervention therapy with RAFA was ineffective at reversing the course of disease after IDDM onset under these experimental conditions. Finally, we report here that prophylactic treatment with RAPA was able to protect against IDDM development in some RAPA-treated mice 41 weeks after cessation of treatment. These data show that orally administered RAPA is effective in preventing onset of disease in the NOD mouse, a relevant model of autoimmune type I diabetes in man.

01 Sep 2005·Journal of Women's HealthQ3 · MEDICINE

Relative Antidepressant Efficacy of Venlafaxine and SSRIs: Sex-Age Interactions

Q3 · MEDICINE

Article

Author: Cantillon, Marc ; Thase, Michael E. ; Kornstein, Susan G. ; Entsuah, Richard

OBJECTIVETo investigate whether differences in antidepressant efficacy are moderated by an interaction of age and gender.METHODSA pooled dataset from eight randomized, controlled trials of patients with major depressive disorder (MDD) was reanalyzed to compare remission rates following therapy with venlafaxine (n = 851), one of several selective serotonin reuptake inhibitors (SSRIs) (n = 748), or placebo (n = 446). Remission was defined as a final Hamilton Rating Scale for Depression (HAM-D) score < or =7. Pairwise comparisons were conducted using stepwise multiple logistic regression models with main effect and interaction terms for treatment, sex, and age (younger: <50; older: > or =50). Among older women, the impact of hormone replacement therapy (HRT) on remission rates also was examined.RESULTSRemission rates on venlafaxine therapy were not affected by age, sex, or HRT use. Among women, but not men, there was a significant interaction reflecting poorer SSRI response in the older age group (Wald chi-square = 4.21, df = 1, p = 0.04); HRT appeared to eliminate this difference. Whereas the advantage in remission rates favoring venlafaxine was modest for men and younger women (6%-9%), the difference among older women not taking HRT was 23%.CONCLUSIONSThese findings provide further evidence that age, gender, and HRT moderate response to antidepressant medications.

01 Sep 2003·Biochemical Society Symposia

Substrate specificity and inducibility of TACE (tumour necrosis factor α-converting enzyme) revisited: the Ala-Val preference, and induced intrinsic activity

Review

Author: Guo, Lin ; Peschon, Jacques J. ; Johnson, Richard ; Virca, Duke ; Sunnarborg, Susan W. ; Jin, Guixian ; Paxton, Ray ; Cowling, Rebecca ; Doedens, John R. ; Charrier, Keith ; Lee, David C. ; Castner, Beverly ; Eisenman, June ; Slack, Jennifer ; Mahimkar, Rajeev ; Wallace, Alison ; Black, Roy A.

Tumour necrosis factor α (TNFα)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor α, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.

100 Deals associated with Wyeth-Ayerst Research

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100 Translational Medicine associated with Wyeth-Ayerst Research

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Pipeline

Pipeline Snapshot as of 22 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Discovery

1

10

Preclinical

Other

1

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

Ritolukast ( CysLT1 )	Inflammation More	Preclinical
WY-46016 ( CysLT1 )	Asthma More	Preclinical
Wy-49353 ( CysLT1 )	Asthma More	Preclinical
Wy-48422 ( CysLT1 )	Asthma More	Preclinical
AY-31906 ( Na/K-ATPase )	Hypertension More	Preclinical