Principles of entrepreneurship (ENT 530): Business model canvas: The Dee Dee’s Chocolate / Shawn O’Neill Anak Kelly

The Dee Dee’s Chocolate are established in the end of the 2019 year. It is a business that are selling popular foods that are usually in high demand during public holidays which is in Raya and Gawai Festive season. Besides this business is a partnership business as the owner of this company which is Shawn O’niel anak Kellly as an owner and with it’s her partnership with his mother which is Nora anak Nanta. It is established due to his mother want to have a business which is selling food. This is because due to her business experience at her young age, it gets the attention of his son. Therefore, its owner is willingly help his mother to fulfil her ambition due to his son has the same passion as her. Besides that, we start selling our product at the end of 2019 till this day. Even though there are some calamities that makes a difficulty to sell our product, it is not enough to break our determination to do our best to make our business to become successful than before. As we can see from the festive season that will be coming soon on June, it is a perfect opportunity to sell our product due to its high demand from people especially at the Kota Samarahan area. Even though there are some slides up and down within our business, we are able to execute our business task with a little difficulty. This is because we are selling our product at reasonable price but at high quality that can satisfy the needs of our customer. Despite having a competitor that sells similar product as us within the Samarahan area, it gives us a healthy competition between each other as it has its own pro and cons while executing the business. In order to keep up with other competitor advantages, we offer a delivery service of our product towards our customer in order to keep our business in good condition. Due to its good feedback from our customer, it shows a positive sign to our business to operate in a long period of time. Without the feedback and critics from our customer, our businesses might not be as successful as it happens on this day. Thus, it gives us a chance to fulfil our goals to be a successful company that are selling the Kuih Chocolate Almond London and Chocolate Cookies without having a problem

Identification of a Novel Positron Emission Tomography (PET) Ligand for Imaging β‑Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE-1) in Brain

Alzheimer’s disease (AD) is characterized by accumulation of β-amyloid (Aβ) plaques and neurofibrillary tau tangles in the brain. β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) plays a key role in the generation of Aβ fragments via extracellular cleavage of the amyloid precursor protein (APP). We became interested in developing a BACE1 PET ligand to facilitate clinical assessment of BACE1 inhibitors and explore its potential in the profiling and selection of patients for AD trials. Using a set of PET ligand design parameters, compound <b>3</b> (PF-06684511) was rapidly identified as a lead with favorable in vitro attributes and structural handles for PET radiolabeling. Further evaluation in an LC-MS/MS “cold tracer” study in rodents revealed high specific binding to BACE1 in brain. Upon radiolabeling, [¹⁸F]<b>3</b> demonstrated favorable brain uptake and high in vivo specificity in nonhuman primate (NHP), suggesting its potential for imaging BACE1 in humans

Identification of a Novel Positron Emission Tomography (PET) Ligand for Imaging β‑Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE-1) in Brain

Alzheimer’s disease (AD) is characterized by accumulation of β-amyloid (Aβ) plaques and neurofibrillary tau tangles in the brain. β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) plays a key role in the generation of Aβ fragments via extracellular cleavage of the amyloid precursor protein (APP). We became interested in developing a BACE1 PET ligand to facilitate clinical assessment of BACE1 inhibitors and explore its potential in the profiling and selection of patients for AD trials. Using a set of PET ligand design parameters, compound <b>3</b> (PF-06684511) was rapidly identified as a lead with favorable in vitro attributes and structural handles for PET radiolabeling. Further evaluation in an LC-MS/MS “cold tracer” study in rodents revealed high specific binding to BACE1 in brain. Upon radiolabeling, [¹⁸F]<b>3</b> demonstrated favorable brain uptake and high in vivo specificity in nonhuman primate (NHP), suggesting its potential for imaging BACE1 in humans

Design and Synthesis of Clinical Candidate PF-06751979: A Potent, Brain Penetrant, β‑Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitor Lacking Hypopigmentation

A major challenge in the development of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors for the treatment of Alzheimer’s disease is the alignment of potency, drug-like properties, and selectivity over related aspartyl proteases such as Cathepsin D (CatD) and BACE2. The potential liabilities of inhibiting BACE2 chronically have only recently begun to emerge as BACE2 impacts the processing of the premelanosome protein (PMEL17) and disrupts melanosome morphology resulting in a depigmentation phenotype. Herein, we describe the identification of clinical candidate PF-06751979 (<b>64</b>), which displays excellent brain penetration, potent in vivo efficacy, and broad selectivity over related aspartyl proteases including BACE2. Chronic dosing of <b>64</b> for up to 9 months in dog did not reveal any observation of hair coat color (pigmentation) changes and suggests a key differentiator over current BACE1 inhibitors that are nonselective against BACE2 in later stage clinical development

Design and Synthesis of Clinical Candidate PF-06751979: A Potent, Brain Penetrant, β‑Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitor Lacking Hypopigmentation

A major challenge in the development of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors for the treatment of Alzheimer’s disease is the alignment of potency, drug-like properties, and selectivity over related aspartyl proteases such as Cathepsin D (CatD) and BACE2. The potential liabilities of inhibiting BACE2 chronically have only recently begun to emerge as BACE2 impacts the processing of the premelanosome protein (PMEL17) and disrupts melanosome morphology resulting in a depigmentation phenotype. Herein, we describe the identification of clinical candidate PF-06751979 (<b>64</b>), which displays excellent brain penetration, potent in vivo efficacy, and broad selectivity over related aspartyl proteases including BACE2. Chronic dosing of <b>64</b> for up to 9 months in dog did not reveal any observation of hair coat color (pigmentation) changes and suggests a key differentiator over current BACE1 inhibitors that are nonselective against BACE2 in later stage clinical development