Lanabecestat (formerly known as AZD3293 or LY3314814)

New Drug Approvals

Lanabecestat

• Molecular FormulaC₂₆H₂₈N₄O
• Average mass412.527 Da

Dispiro[cyclohexane-1,2′-[2H]indene-1′(3′H),2”-[2H]imidazol]-4”-amine, 4-methoxy-5”-methyl-6′-[5-(1-propyn-1-yl)-3-pyridinyl]-, (1α,1′R,4β)-

(1r,1’R,4R)-4-Methoxy-5”-methyl-6′-[5-(1-propin-1-yl)-3-pyridinyl]-3’H-dispiro[cyclohexane-1,2′-indene-1′,2”-imidazol]-4”-amin[German][ACD/IUPAC Name]

(1r,1’R,4R)-4-Methoxy-5”-methyl-6′-[5-(1-propyn-1-yl)-3-pyridinyl]-3’H-dispiro[cyclohexane-1,2′-indene-1′,2”-imidazol]-4”-amine[ACD/IUPAC Name]

(lr,l’R,4R)- 4-methoxy-5″-methyl-6′-[5-(prop-l-yn-l-yl)pyridin-3-yl]-3’H- dispiro[cyclohexane-l,2′-inden-l’2′-imidazole]-4″-amine

(lr,4r)-4-Methoxy-5″-methyl-6′-(5-prop-l-yn-l-ylpyridin-3-yl)-3’H-dispiro[cyclohexane- l,2′-indene-l’,2″-imidazol]- “-amine

CAS 1383982-64-6[RN]

AZD3293

Dispiro[cyclohexane-1,2′-[1H]indene-1′(3’H),2”-[2H]imidazol]-4”-amine, 4-methoxy-5”-methyl-6′-[5-(1-propyn-1-yl)-3-pyridinyl]-, (1’R)-

Lanabecestat

LY3314814

UNII:X8SPJ492VF

• (1α,1’R,4β)-4-Methoxy-5”-methyl-6′-[5-(1-propyn-1-yl)-3-pyridinyl]dispiro[cyclohexane-1,2′-[2H]indene-1′(3’H),2”-[2H]imidazol]-4”-amine
• (1,4-trans,1’R)-4-methoxy-5”-methyl-6′-[5-(prop-1-yn-1-yl)pyridin-3-yl]-3’H-dispiro[cyclohexane-1,2′-indene-1′,2”-imidazol]-4”-amine
• (1r,1’R,4R)-4-methoxy-5”-methyl-6′-[5-(prop-1-yn-1-yl)pyridin-3-yl]-3’H-dispiro[cyclohexane-1,2′-indene-1′,2”-imidazol]-4”-amine

Lanabecestat (formerly known as AZD3293 or LY3314814) is an oral beta-secretase 1 cleaving enzyme (BACE) inhibitor. A BACE inhibitor in theory would prevent the buildup of beta-amyloid and may help slow or stop the progression of Alzheimer’s disease.

In September 2014, AstraZeneca and Eli Lilly and Company announced an agreement to co-develop lanabecestat.^[1] A pivotal Phase II/III clinical trial of lanabecestat started in late 2014 and is planned to recruit 2,200 patients and end in June 2019.^[2] In April 2016 the company announced it would advance to phase 3 without modification.^[3]

• OriginatorAstex Pharmaceuticals…

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A review of fungal contamination in pharmaceutical products and phenotypic identification of contaminants by conventional methods

Article (PDF Available) in European Journal of Parenteral and Pharmaceutical Sciences 17(1):4-19 · January 2011

Abstract

Microbial contamination of pharmaceutical products is one of the major reasons for product recall and manufacturing problems. Knowledge of the distribution of survival microorganisms in pharmaceutical environments is critical in the process control of non sterile and sterile pharmaceutical products. This knowledge is somewhat limited by the ubiquitous distribution of microorganisms in manufacturing facilities particularly fungal distribution. Identification of these fungi isolates from pharmaceutical environments using standard identification procedures requires experienced skilled technologists. To develop the proper corrective action when out of specification results are obtained, accurate fungal identification is needed if the contamination source has to be determined and tracked. Corrective action may not be effective if erroneous information is used to solve a given problem. This review provides guidance about knowledge of fungal contamination in pharmaceutical products and outlines an economic approach to phenotypic identification using conventional methods.

A review of fungal contamination in pharmaceutical products and phenotypic identification of contaminants by conventional methods (PDF Download Available). Available from: https://www.researchgate.net/publication/275335972_A_review_of_fungal_contamination_in_pharmaceutical_products_and_phenotypic_identification_of_contaminants_by_conventional_methods [accessed Jun 12, 2017].

https://www.researchgate.net/publication/275335972_A_review_of_fungal_contamination_in_pharmaceutical_products_and_phenotypic_identification_of_contaminants_by_conventional_methods

REFERENCES

Click to access chapter%202.pdf

Any pharmaceutical product, whether manufactured in the hospital or industrial environment, has the potential to be contaminated with microorganisms. With sterile products, any microbial contamination presents an unacceptable risk; with non-sterile products, the implication of the contamination is dependent upon whether the microorganism can be considered ‘objectionable’, and then to the extent that it can cause patient harm (and here a risk assessment is ordinarily required)¹.

There are different types of microorganisms associated with product recalls. At this stage into the 21st century, fungal contamination of nonsterile products is one of the major reasons for product recalls, production shutdowns, and losses in labour and manufacturing. This can result in a reduced shelf life by compromising product integrity or present potential health hazard to patients². Many of the reasons are due to the lack of quality control, process control and proper testing.

Most reports relating to the contamination of pharmaceutical products centre on bacterial contamination rather than fungi. The reasons for this may relate to few ‘microbiology’ laboratories in pharmaceutical organisations having trained mycologists; to an underestimation of the association between fungi and product contamination incidents; and due to a lack of appreciation of the risks that fungi can pose to cleanrooms and controlled environments³. This article considers some of these issues and, in doing so, argues that the contamination risk posed by fungi to pharmaceutical products is greater than the level of industrial and academic interest would suggest.

Fungal contamination risks

Fungi are more evolutionarily advanced forms of microorganisms, as compared to the prokaryotes (such as bacteria). Fungi are commonly divided into two distinct morphological forms: yeasts and hyphae (or filamentous). Yeasts are unicellular fungi which reproduce asexually by blastoconidia formation (budding) or fission⁴. Fungal contamination in pharmaceutical products represents a potential hazard for two reasons. First, it may cause product spoilage; the metabolic versatility of fungi is such that any formulation ingredient from simple sugars to complex aromatic molecules may undergo chemical modification in the presence of a suitable organism. Spoilage will not only affect therapeutic properties of the product but may also discourage the patient from taking the medication. Second, product contamination represents a health hazard to the patient, although the extent of the hazard will vary from product to product and patient to patient, depending on the types and numbers of organisms present, the route of administration, and the resistance of the patient to infection. https://www.europeanpharmaceuticalreview.com/24118/topics/microbiology-rmm/fungal-contamination-pharmaceutical-products-growing-menace/

Tim Sandle

The University of Manchester , Manchester

Microbiology, Biotechnology

PhD

Vijayakumar Rajendran

Majmaah University , Riyadh

Immunology, Biotechnology, Mycology

Ph.D