ACE inhibitors(Angiotensin-converting enzyme inhibitors), α7 receptor antagonists(Neuronal acetylcholine receptor protein alpha-7 subunit antagonists)

Therapeutic Areas

Cardiovascular Diseases

Active Indication-

Inactive Indication

Hypertension

Originator Organization

Sanofi

Active Organization-

Inactive Organization

Sanofi

Atos SE

Drug Highest PhaseDiscontinuedPhase 1

First Approval Date-

Regulation-

Structure

Molecular FormulaC14H19NO3S

InChIKeyABBSOQIXYPZCKO-NHCYSSNCSA-N

CAS Registry155895-89-9

100 Clinical Results associated with RB-105

100 Translational Medicine associated with RB-105

100 Patents (Medical) associated with RB-105

Literatures (Medical) associated with RB-105

01 Oct 2006·Microbial PathogenesisQ3 · MEDICINE

An epitope shared by cellular cytokeratin and Orientia tsutsugamushi

Q3 · MEDICINE

Article

Author: Jae-Seung Kang ; Mee-Kyung Kim ; Mi-Jeong Kim

Many microbial pathogens have epitopes shared with host cell components and these epitopes may induce transient or longer-term tissue-damaging autoantibody responses. We observed that several mouse monoclonal antibodies (MAbs) raised against Orientia tsutsugamushi were also reactive with host cells. One such antibody, MAb Rb105, cross-reacted with the cytoskeleton, as shown by immunofluorescent staining. Biochemical studies identified the cross-reacting component as a cytokeratin protein. These results identify an epitope shared by O. tsutsugamushi and the cytokeratins of host cells. In addition, antibodies cross-reactive with the cytoskeleton were detected in the sera of scrub typhus patients, suggesting that an epitope similar to that detected by MAb Rb105 may be recognized by human antibodies.

01 Jun 2002·Clinical Pharmacology & TherapeuticsQ2 · MEDICINE

Renal and vascular effects of S21402, a dual inhibitor of angiotensin‐converting enzyme and neutral endopeptidase, in healthy subjects with hypovolemia

Q2 · MEDICINE

Article

Author: Ragueneau, Isabelle ; Jaillon, Patrice ; Tharaux, Pierre-Louis ; Dussaule, Jean-Claude ; Chodjania, Yasmina ; Picker, Jean-Luc ; Funck-Brentano, Christian

ObjectiveTo examine the mechanism of action of dual inhibitors of angiotensin‐converting enzyme (ACE) and neutral endopeptidase, also called vasopeptidase inhibitors, we compared the effects of S21402 [(2S)‐2‐{(2S,3R)‐2‐thiomethyl‐3‐phenylbutanamido}propionic acid], which belongs to this pharmacologic class, with those of captopril, an ACE inhibitor, on blood pressure, endocrine parameters, and renal in healthy subjects with hypovolemia.MethodsTen subjects participated to this double‐blind, 2‐period, randomized, crossover study. Hypovolemia was induced in these subjects with a 7‐day treatment of hydrochlorothiazide. They received a single oral dose of 50 mg captopril or 250 mg S21402 on the last day of diuretic treatment. Blood pressure was measured, and urine and blood samples were collected before and during a 12‐hour period after drug administration.ResultsThe plasma angiotensin II/angiotensin I ratio and aldosterone concentration decreased to the same degree with both drugs, 3 hours after dosing. Compared with captopril, S21402 increased levels of plasma atrial natriuretic peptide (P < .05) and urinary cyclic guanosine monophosphate (P < .001); these increases were the result of inhibition of neutral endopeptidase activity (P < .001). The increase in plasma renin concentration related to ACE inhibition was less marked (P < .001) after S21402 than after captopril. S21402, but not captopril, increased urinary sodium excretion (P < .05), without modifying blood pressure and creatinine clearance, whereas blood pressure transiently fell after ceptopril administration (P < .05).ConclusionsIn healthy hypovolemic subjects, the vasopeptidase inhibitor S21402 exhibits a natriuretic effect and does not affect blood pressure or glomerular filtration rate. In these conditions, the acute endocrine, vascular, and renal effects of vasopeptidase inhibition differ from those of ACE inhibition.Clinical Pharmacology & Therapeutics (2002) 71, 468–478; doi: 10.1067/mcp.2002.124521

01 Apr 2002·Journal of HypertensionQ2 · MEDICINE

Combined inhibition of neutral endopeptidase with angiotensin converting enzyme or endothelin converting enzyme in experimental diabetes

Q2 · MEDICINE

Article

Author: Markus Lassila ; Tuula Tikkanen ; Mark E Cooper ; Zemin Cao ; Louise M Burrell ; David J Casley ; Colin I Johnston ; Belinda J Davis ; Terri J Allen ; Ilkka Tikkanen

OBJECTIVEThe effects of combined inhibition of neutral endopeptidase (NEP) with either angiotensin-converting enzyme (ACE), or endothelin-converting enzyme (ECE) on blood pressure, urinary albumin excretion and heart weight were explored in experimental diabetes.DESIGNStreptozotocin-induced diabetic Sprague-Dawley rats were treated with vehicle, the NEP/ACE inhibitor S 21402, the NEP/ECE inhibitor CGS 26303, the NEP inhibitor SCH 42495, the ACE inhibitor captopril or the endothelin receptor antagonist bosentan for 4 weeks.METHODSBlood pressure was measured by tail-cuff method and radiotelemetry. Albuminuria, plasma renin activity and plasma atrial natriuretic peptide (ANP) were determined by radioimmunoassay. NEP binding was assessed by in vitro quantitative autoradiography. Metabolic and biochemistry parameters including food intake, 24-h urine volume, plasma glucose, glycated hemoglobin, glomerular filtration rate (GFR) and urinary sodium excretion were also determined.RESULTSMean blood pressure over the 4-week study period after commencement of treatment was reduced to a similar extent by a range of treatments including the ACE inhibitor, NEP/ACE inhibitor, endothelin receptor antagonist, NEP/ECE inhibitor, but not the NEP inhibitor, compared with vehicle-treated diabetic rats. Heart to body weight ratio in diabetic rats was only reduced by the NEP/ACE and the NEP/ECE inhibitor. Increased albuminuria in diabetic rats (1.1 times/divided by 1.2 mg/day) was reduced by the NEP/ACE (0.6 times/divided by 1.2 mg/day) and the NEP/ECE inhibitors (0.4 times/divided by 1.2 mg/day). Renal NEP was reduced by the NEP/ACE inhibitor (35 +/- 4%) or NEP/ECE inhibitor (38 +/- 4%) as well as by the pure NEP inhibitor (27 +/- 4%) compared with the untreated diabetic group. Other abnormal metabolic and biochemical parameters in diabetic rats were not influenced by any drug treatment.CONCLUSIONSCombined inhibition of NEP/ACE or NEP/ECE confers beneficial effects on blood pressure, albuminuria and heart to body weight ratio in experimental diabetes.

100 Deals associated with RB-105

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Indication	Highest Phase	Country/Location	Organization	Date
Hypertension	Phase 1	-	Sanofi	-
Hypertension	Phase 1	-	Atos SE	-

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