Delving into the Latest Updates on Cetilistat with Synapse

Author: Morales‐Garcia, Flavia ; Collins, Melissa ; Gonzalez Illan, Fernando ; LaGarde, Donna ; Loh, Mark ; Reimer, Allison M. ; Wetherby, Anthony E. ; Batson, JaCinta ; Howe, Gregory ; Lanzarotta, Adam ; Sterling, Megan E. ; Kern, Sara ; Arrecis, Julio ; Lorenz, Lisa ; Hudson‐Davis, Morgan ; Kimani, Martin ; Thatcher, Michael ; Altaf, Muhammad ; Boyd, Brian ; Griffin, Kelsey M. ; Laguerre, David ; Patel, Anvi

AbstractTwo chemists employed a three‐device rapid screening “toolkit” consisting of a handheld Raman spectrometer, transportable mass spectrometer, and portable Fourier transform infrared (FT‐IR) spectrometer at an international mail facility (IMF) satellite laboratory to examine unknown (unlabeled/mislabeled) products for the presence of active pharmaceutical ingredients (APIs). Phase I of this project previously demonstrated that this toolkit was the most effective collection of instruments for identifying APIs in product types collected at IMFs during a nationwide mail blitz and Phase II of this project previously demonstrated that results generated using the toolkit during a satellite laboratory pilot program were as reliable as those generated by a full‐service library when two or more of these instruments identify an API. This study (Phase III) described the results of the satellite laboratory toolkit during production mode and encompassed the period ranging from June 2021 through December 2022. During this study, a total of 858 products were examined on‐site at the IMF. The satellite laboratory yielded conclusive results for 726 (84.6%) products, which were used to support regulatory action, and identified 132 (15.4%) products that required additional full‐service laboratory analyses due to inconclusive results. The satellite and full‐service laboratory verified/confirmed at least one API/related substance in 617 (71.9%) products. A total of 709 APIs/related substances were found in the 617 products, and 202 of these 709 compounds were unique/different. Overall, during Phases I through III of this program, 350 different substances have been identified in products collected at IMFs.

01 May 2024·Hormones and Behavior

Pterostilbene alleviates cafeteria diet-induced obesity and underlying depression in adolescent male Swiss albino mice and affects insulin resistance, inflammation, HPA axis dysfunction and SIRT1 mediated leptin-ghrelin signaling

Article

Author: Aswar, Urmila ; Vyas, Nishant ; Patil, Rashmi

Cafeteria diet (CD) model for in-vivo studies mimics the western diet having imbalanced nutritional value, high caloric-density and palatability. Uncontrolled eating leads to the development of childhood obesity, poor self-esteem and depression due to its effects on brain development. Herbal supplements are novel inclusion in the management of obesity and mental well-being. Pterostilbene (PTE) found in blueberries and Pterocarpus marsupium heartwood, is known to prevent obesity in invivo models. Adolescent Swiss albino male mice were fed on CD for 70 days and the development of obesity was assessed by gain in body weight, abdominal circumference. Forced swim and tail suspension test confirmed depression in CD fed mice. Obesity induced depressed (OID) mice were treated with PTE (10, 20, 40 mg/kg), standard antiobesity drug cetilistat (10 mg/kg), antidepressant fluoxetine (10 mg/kg) for 28 days. Post treatment, PTE-treated mice showed reduction in BW and depression-like behavior analysed using paradigms such as sucrose preference, open field, marble burying, and resident intruder test in comparison to the CD group. Insulin resistance, lipid profile, antioxidant enzyme, inflammatory cytokines (NF-κB, IL-6, TNF α) and cortisol levels were mitigated by PTE. It also restored normal cellular architecture of the brain and adipose tissue and increased the Silent mating type information regulation 2 homolog1 (SIRT1), leptin and ghrelin receptors gene expression in the brain. Thus, it can be concluded that PTE might have inhibited OID like behavior in mice via inhibition of IR, modulating neuroinflammation and hypothalamic-pituitary-adrenal axis dysfunction and upregulating SIRT1 mediated leptin-ghrelin signaling.

30 Mar 2023·Scientific reports

Metabolic profiling, antioxidant, and enzyme inhibition potential of Iris pseudacorus L. from Egypt and Japan: A comparative study.

Article

Author: Ayoub, Iriny M ; Devkota, Hari Prasad ; Singab, Abdel Nasser B ; Watanabe, Masato ; Yehia, Suzan M

Genus Iris comprises numerous and diverse phytoconstituents displaying marked biological activities. The rhizomes, and aerial parts of Iris pseudacorus L. cultivars from Egypt and Japan were subjected to comparative metabolic profiling using UPLC-ESI-MS/MS. The antioxidant capacity was determined using DPPH assay. In vitro enzyme inhibition potential against α-glucosidase, tyrosinase and lipase was evaluated. In silico molecular docking was conducted on the active sites of human α-glucosidase and human pancreatic lipase. Forty-three compounds were tentatively identified including flavonoids, isoflavonoids, phenolics and xanthones. I. pseudacorus rhizomes extracts (IPR-J and IPR-E) exhibited the highest radical scavenging activity with IC₅₀ values of 40.89 µg/mL and 97.97 µg/mL, respectively (Trolox IC₅₀ value was 14.59 µg/mL). Moreover, IPR-J and IPR-E exhibited promising α-glucosidase inhibitory activity displaying IC₅₀ values of 18.52 µg/mL, 57.89 µg/mL, respectively being more potent as compared to acarbose with IC₅₀ value of 362.088 µg/mL. All extracts exerted significant lipase inhibitory activity exhibiting IC₅₀ values of 2.35, 4.81, 2.22 and 0.42 µg/mL, respectively compared to cetilistat with IC₅₀ value of 7.47 µg/mL. However, no tyrosinase inhibitory activity was observed for all I. pseudacorus extracts up to 500 µg/mL. In silico molecular modelling revealed that quercetin, galloyl glucose, and irilin D exhibited the highest fitting scores within the active sites of human α-glucosidase and pancreatic lipase. ADMET prediction (absorption, distribution, metabolism, excretion, and toxicity) showed that most of the phytoconstituents exhibited promising pharmacokinetic, pharmacodynamics and tolerable toxicity properties. According to our findings, I. pseudacorus might be considered as a valuable source for designing novel phytopharmaceuticals.

100 Deals associated with Cetilistat

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External Link

KEGG	Wiki	ATC	Drug Bank
D09208	Cetilistat	A08A	DB06586

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Obesity	Japan	Takeda Pharmaceutical Co., Ltd.	02 Sep 2013

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Obesity	Preclinical	Europe	Norgine BV	20 Sep 2013
Obesity	Preclinical	Europe	Norgine BV	20 Sep 2013
Type 2 diabetes mellitus in obese	Preclinical	United Kingdom	Alizyme Plc	01 Dec 2004
Type 2 diabetes mellitus in obese	Preclinical	Netherlands	Alizyme Plc	01 Dec 2004
Type 2 diabetes mellitus in obese	Preclinical	Sweden	Alizyme Plc	01 Dec 2004
Type 2 diabetes mellitus in obese	Preclinical	Finland	Alizyme Plc	01 Dec 2004
Type 2 diabetes mellitus in obese	Preclinical	Denmark	Alizyme Plc	01 Dec 2004

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Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00156897 (Pubmed \| Obesity (Silver Spring))	Phase 2	Type 2 diabetes mellitus in obese	-	Cetilistat 40 mg	(ukkmylwfxd) = vrzohseori hylmxstqhq (efbvfazazx )	-	01 Jan 2010
				Cetilistat 80 mg	(ukkmylwfxd) = fesriowywx hylmxstqhq (efbvfazazx )