Glossary

B

Biochemistry: The study of biological phenomena by defining the constituent substances of living organisms and the chemical reactions within organisms. Main subjects of research in this field include the structural determination of biological substances, their action and function, and the mechanics of metabolism.
Bullous Keratopathy: Bullous keratopathy occurs when corneal endothelial cell damage results in a swollen and cloudy cornea, leading to greatly weakened eyesight. It is associated with loss of corneal endothelial cells due to Fuchs’ endothelial corneal dystrophy (FECD) or surgery for cataracts or glaucoma. The recommended treatment is corneal keratoplasty.

C

Cataracts: A condition where the crystalline lens of the eye becomes cloudy and causes visual impairment. The main cause is aging, and if symptoms progress surgery may be done to remove the cloudy crystalline lens and insert an artificial intraocular lens. Approximately 1.2 million cataract surgeries are performed every year in Japan.
Chemical synthesis: Refers to making a compound by means of a chemical reaction of two or more simple substances or compounds.
Clinical development: To bring a new drug to market, Japanese law requires approval by the Ministry of Health, Labour and Welfare (MHLW). To obtain approval, it is necessary to actually administer a new drug candidate to human subjects to confirm its safety and efficacy. Trials carried out to this end are divided into three stages (Phase I, Phase II, and Phase III clinical trials), which are collectively referred to as clinical development.
Compound library: A group of compounds that DWTI has accumulated over the years, which can be used as seeds for drug candidate compounds. Each compound has distinct properties and is used for basic research or for discovery of drug candidate compounds.

D

Derivative: Considering a certain organic compound as a precursor compound, a derivative is a compound that has been modified to the extent that the structure of its precursor is not changed significantly.
Diabetic macular edema: Macular edema is a condition caused by diabetes in which the capillaries of the retina are damaged and elements in the blood (water and protein) leak out, causing the macula, or center of the eye, to swell. Since the macula is a very important part of vision, if macular edema extends over a long period without being treated it can cause significant loss of vision, and lead to severe visual impairment or blindness.
Diabetic retinopathy: A condition brought about by diabetes in which the retina is injured, vision is impaired, and blindness occurs. Diabetic retinopathy is said to be one of the three most serious complications of diabetes, along with diabetic neuropathy and diabetic nephropathy.
Drug-Western Method: A method used to identify the target protein of a drug, which DWTI invented by applying our biotechnology, and for which we previously held the patent. The method is able to identify a target protein without going through a cumbersome process of protein purification, by detecting a small amount of protein to which a drug binds and identifying its genetic makeup.

F

First-in-class: A groundbreaking new drug. First-in-class refers to a drug that offers particular usefulness even for a new drug; it indicates a drug that brings about a change in treatment systems or an original and groundbreaking new drug that has no precedent.
Fuchs endothelial corneal dystrophy (FECD): FECD is a disease in which corneal endothelial cells are damaged, causing corneal edema and opacity, and diminished visual acuity. It is a common disease in Europe and the U.S., although there are few FECD sufferers in Japan. The only current treatment for FECD is corneal transplantation, and the development of an effective drug treatment is much anticipated.

G

Glaucoma, ocular hypertension: Glaucoma is a disease marked by distinctive changes to the optic nerves and visual field. It is characterized by functional and structural abnormalities of the eye, wherein optic nerve damage can normally be improved or contained by sufficiently lowering intraocular pressure. If left untreated, symptoms may range from narrowing of the visual field to blindness. Glaucoma is the number one cause of adult-onset blindness in Japan. Ocular hypertension is a condition in which intraocular pressure exceeds normal levels although there is no narrowing of the visual field. Currently, the only reliable, evidence-based treatment for glaucoma is lowering intraocular pressure. Drug treatments are the first choice for treating primary open-angle glaucoma (in a broad sense).

I

Identification: Refers to determining the target of an isolated chemical substance or other element.
Inhibitor: A substance that binds to various enzyme molecules in the body and reduces or eliminates the activity of the enzyme. Because they reduce or eliminate the activity of certain enzymes, these chemical substances may find use as treatments for diseases.
In-licensed product: Refers to a product developed in-house using the drug candidate compound of another company. The original company holds the rights to the compound, but regarding patent rights and gained expertise, etc., the in-licensing company holds the right of exercise.
Intracellular signal transduction: A system that transmits signals from outside a cell, such as nerve stimulation or hormones, to a target location inside the cell.
Investigator-initiated clinical trial: A clinical trial carried out primarily by doctors and medical institutions.
Isoquinoline sulfonamide compound: The name of the skeletal structure (shape) of a compound DWTI is developing.

L

Launch: The stage when a new drug is approved and actually put on the market.
Lidocaine: A type of local anesthetic that reduces pain by blocking pain signals at nerve endings.
LRRK: Leucine-rich repeat kinase, a protein with kinase activity. Because genetic mutations that cause heightened kinase activity are frequently detected in patients with autosomal dominant Parkinson’s disease, this protein is considered to be an important molecule involved in the disease. LRRK is expressed in many tissue types as well as in the trabecular meshwork of the eye, suggesting that the protein is involved in regulating the cytoskeleton.

M

Mechanism of action: Refers to the mechanism by which a drug acts. In recent years, the importance of clarifying drug action has increased, and elucidating mechanisms of action is gaining attention in new drug development.
Modality: As drug discovery research grows increasingly diverse, modality refers to a range of approaches to drug discovery (methods and technologies), such as small molecule drugs, peptide drugs, antibody drugs, nucleotide drugs, cell therapy, and regenerative medicine.
Molecular pharmacology: Pharmacology uses drugs to clarify the functions of living organisms, investigating the mechanisms by which a drug has an influence or effect on an organism. Molecular pharmacology has as its subject of pharmacological investigation the building blocks of living organisms at the smallest level without loss of chemical properties, i.e., at the genetic level.
Multi-kinase inhibitor: A drug that has an inhibiting effect on multiple kinases. The H-1337 compound inhibits various protein kinases centering on LRRK2.

N

Neuropathic pain treatment: A drug used to treat neuropathic pain brought about by nerve damage resulting from some cause. Neuropathic pain is thought to be caused by the excessive release of pain-transmitting substances called neurotransmitters. Neuropathic pain treatments alleviate pain by suppressing the release of such neurotransmitters.
New drug applicant: Refers to a pharmaceutical manufacturer or distributor seeking to have a new drug listed on the NHI drug price standard.
NHI drug price listing: Indicates listing on the NHI drug price standard, which is a list of official prices set by the Ministry of Health, Labour and Welfare (MHLW) for new drugs and generic drugs approved by the MHLW for manufacture and sale. NHI listing makes drugs prescribed at hospitals and other medical institutions eligible for national health insurance coverage.
Nonclinical trial (preclinical trial): A trial using experimental animals for the purpose of verifying the adverse reactions, safety, and stability of a substance under the conditions that must be met for its use as a pharmaceutical drug.

O

Open innovation: A phrase meaning creating new value (services, products, etc.) by using not only internal but also external technology, ideas, expertise, and other resources.
Out-licensing: Licensing to another company the patent rights and expertise related to drug candidate compounds that have been researched and developed up to a certain stage.

P

Phase I clinical trial: A trial, using healthy human subjects, to test the safety of a drug candidate compound and adverse reactions in the body.
Phase II clinical trial: A trial involving a small patient sample size to confirm the safety and efficacy of a drug candidate compound (early Phase II), and to examine the minimum effective dose and regimen (late Phase II).
Phase III clinical trial: A trial involving a large patient sample size in which a drug candidate is administered as a treatment for a disease under the conditions that must be met for its use in clinical settings, and outcomes are compared with existing drugs and/or placebos.
Pipeline: Refers to a series of potential product lines ranging from new drug candidates under development to products launched onto the market. Sometimes it simply refers to an individual new drug candidate.
Protein kinase: Enzymes that transfer phosphate groups from such substances as low molecular substances that are energy sources in living organisms, including adenosine triphosphate (ATP, a high-energy compound produced in the body), in a process called phosphorylation. Enzymes that catalyze phosphorylation are generally called kinases; kinases that act on proteins are called protein kinases.
Protein phosphorylation: A chemical reaction in which a phosphate group is transferred to a protein, which is thought to regulate the protein’s function.
Pulmonary hypertension: A disease in which pressure in the blood vessels going from the heart to the lungs (pulmonary arteries) increases. It is a rare disease with no known cure, which not only causes shortness of breath and dyspnea, but can also put strain on the heart which may lead to right heart failure if it progresses. Among disease types, the number of patients with pulmonary arterial hypertension, the main type of pulmonary hypertension, is said to be about 3,000 (in Japan), and is increasing every year.

R

Retinopathy of prematurity (ROP): ROP is a condition that affects low-birth-weight infants. After birth, premature infants are placed in an incubator, a high oxygen environment. When they return to a normal environment, their bodies try to rapidly produce blood vessels to adapt. This also occurs in the retina, where the rapid growth of blood vessels may result in the formation of fragile, abnormal blood vessels. This can lead to retinal detachment and ultimately to blindness. Currently, the condition is treated with laser therapy, but this is not a satisfactory treatment, as it does not necessarily restore eyesight.
Rho kinase: Rho kinase is one of the family of protein phosphorylation enzymes (protein kinases), and is involved in the control mechanism of various cellular responses via the Rho-ROCK pathway.

S

Screening: Developing a new drug necessitates selecting an effective and highly safe compound from among a large number of candidate compounds. Screening refers to a series of steps to search for new drug candidates out of a large number of compounds.

T

Target protein: The protein upon which a drug acts. In a living organism, multiple proteins interact to perform various functions, and many diseases are caused by the abnormal action of specific proteins. For such diseases, it is thought that drugs which target these specific proteins and suppress their abnormal action can be effective.
Toxicity screening: Refers to testing for toxicity by means of (a) reverse mutation tests using bacteria, (b) chromosomal aberration tests using cultured mammalian cells, and (c) 28-day repeated dose toxicity tests using mammals. Reverse mutation tests use bacteria to test mutagenicity, or changes rendered to genes by means of chemical substances, including carcinogenicity.　Because bacteria lack a clear chromosomal structure and so cannot be used to detect aberrations, chromosomal aberration tests use the cells of mammals cultured in vitro to check for genotoxicity to chromosomes. Repeated dose toxicity tests observe changes in biological function and morphology that appear when repeated doses are administered to rats or other animals daily over a certain period.

U

Unmet medical needs: Medical needs that have not yet been addressed, which means that no effective drug or therapy yet exists, even though patients or the medical field strongly hope for a treatment.