Drug Development Process PDF

**DRUG DEVELOPMENT** - This is the term used to define the entire process of bringing a new drug or device to the market. *This is a strenuous process.* - It is a multidisciplinary endeavor that includes drug discovery, chemistry and pharmacology, nonclinical safety testing, animal...

**DRUG DEVELOPMENT** - This is the term used to define the entire process of bringing a new drug or device to the market. *This is a strenuous process.* - It is a multidisciplinary endeavor that includes drug discovery, chemistry and pharmacology, nonclinical safety testing, animal testing, manufacturing, clinical trials, and regulatory submissions. - IT IS VERY COSTLY -- *because of [Trial and Error.]* - In 10,000 NCEs (New Chemical Entities) investigated to potentially treat diseases, only 250 make it to animal testing stage, then only 5-10 would qualify for testing in human patients. - Only, 1-2 products out of the original 10,000 NCEs are deemed marketable. **DRUG DEVELOPMENT PROCESS** 1. **DISCOVERY AND DEVELOPMENT -- *More on research*** 2. **PRECLINICAL RESEARCH -- *Involves Animal Testing*** 3. **CLINICAL RESEARCH - *Human Testing*** 4. **FDA REVIEW** 5. **FDA POST-MARKET SAFETY MONITORING** **STEP 1: DISCOVERY AND DEVELOPMENT** **DISCOVERY** 1. New insights into a disease process that allow researchers to design a product to stop or reverse the effect of disease 2. Many tests done to chemicals, molecular compounds, plant phytochemicals and etc. in finding possible beneficial effects against any of a large number of diseases 3. Existing treatments that have unanticipated effects. 4. New technologies such as those that provide new ways to target medical products to specific sites within the body or to manipulate genetic material. - At this stage in the process, thousands of compounds may be potential candidates for development as a medical treatment. After early testing, however, only a small number of compounds look promising and call for further study. - ***Drug Repurposing:** existing treatment that have unanticipated effects; the process of using an existing drug or drug candidate for a new treatment or medical condition for which it was not indicated before. Example:* A. ***Raloxifene** -\> for osteoporosis -\> for post-menopausal breast cancer* B. ***Sildenafil** -\> for pulmonary hypertension -\> performance enhancer, treat erectile dysfunction* **DEVELOPMENT** **Once researchers identify a promising compound for development, they conduct experiments to gather information on:** - **How it is absorbed, distributed, metabolized, and excreted.** - **Its potential benefits and mechanisms of action.** - **The best dosage.** - **The best way to give the drug (such as by mouth or injection).** - **Side effects or adverse events that can often be referred to as toxicity.** - **How it affects different groups of people (such as by gender, race, or ethnicity) differently.** - **How it interacts with other drugs and treatments.** - **Its effectiveness as compared with similar drugs** **STEP 2: PRECLINICAL RESEARCH** **Before testing a drug in people, researchers must find out whether it has the potential to cause serious harm, also called toxicity. The two types of preclinical research are:** 1. **In Vitro: Research done in a laboratory dish or test tubes** 2. **In Vivo: Research done on a living organism. (Microorganisms, Tissues, Plants or Animals)** **ANIMALS USED IN EXPERIMENTAL PHARMACOLOGY** **(*S. Sivakrishnan, S. Vigil Anbiah*)** 1. **ALBINO RATS** - **One of the commonest laboratory animals because of their small size and greater sensitivity to most drugs.** - **[Experimental Use:] Analgesic and anticonvulsant studies, bioassays of various hormones such as insulin, oxytocin, and vasopressin, chronic blood pressure studies, gastric acid secretion studies, acute and chronic toxicity studies. The rats are ideal for determining the teratogenicity and carcinogenicity of drugs.** - **Tissues of Rat used for various drug actions** 2. **GUINEA PIGS** - In many respects, the guinea pig differs from other laboratory rodents. It needs Vitamin C in the diet and is very susceptible to anaphylactic shock and tuberculosis. - Highly sensitive to histamine. - Used to separate various bacterial strains in the past, but they have been replaced by mice and rats in modem laboratories, which replicate faster. - *[Experimental Use]:* - It is mainly used for the evaluation of the bronchodilator drugs against experimentally induced asthma (histamine or acetylcholine aerosols). - It is also used in the field of immunology particularly in the area of delayed hypersensitivity by using various antigens such as egg albumin, horse serum, etc. - Widely used in the studies of the local anesthetics as well as the bioassay of digitalis and suitable for hearing experiments as they have sensitive cochlea and experiments on oxygen consumption. - It resembles a man in that it also needs an exogenous source of vitamin C and so it is useful in the study of its metabolism - Being an appropriate host for **Mycobacterium**, it is also suitable for **tuberculosis studies.** - *[Various Isolated Tissues of Guinea Pig:]* - Isolated organ preparations such as guinea pig lungs and intestines are widely used. - These organ and tissue preparations were considerable in the discovery and early development of medicines to treat stomach ulcers and also beta-blockers to treat high blood pressure. - The terminal ileum is most sensitive for the preliminary screening of the spasmodic and antispasmodic compounds and suitable for the detection and assay of histamine and related compounds. 3. **MOUSE (*Mus musculus*)** - Albino mice are the smallest laboratory animals, which can be bred uniformly. - *[Experimental Use]*: - Widely useful in acute toxicity studies. - Also used in the assay of insulin and analgesics and also for the general screening of the chemotherapeutic agents specially bred mice arc mainly useful in the study of problems in genetics and cancer. - Most frequently used for testing drugs due to teratogenicity - The Nude mice which lack the thymus gland are mainly useful in the study of tissue immunity and transplantation research 4. **RABBITS** - *[Experimental Use:]* - Mainly used for **pyrogen testing** in intravenous fluids. - Studies of miotics and mydriatic - Insulin and other antidiabetic drugs - Curare -- *Muscle relaxant* - Sex hormones - *[Used Tissues of Rabbit:]* Isolated heart, Jejunum, and ileum are some of the preparations routinely used for the testing of the drugs. 5. **HAMSTER** - *[Experimental Use:]* - Among other research fields, including oncology, immunology, and physiology, the hamster is widely used in IVF (In-Vitro Fertilization) research. However, their peculiar reproductive system involves a continuous 4-day estrous cycle (all non-higher primate mammals\' reproductive cycle) and a very short 16-day pregnancy period. 6. **CATS** - The smallest member of the feline family. - Cats also suffer from diseases such as leukemia, Alzheimer\'s disease, heart disease, infection, and immunodeficiency, and thus, they are excellent animal models for the mentioned diseases. - Their relatively long lifespan of 20 years also makes them ideal models for illnesses and disorders that are age-related and slowly evolving. - In cats, morphine produces excitation of the CNS. - *[Experimental Use]:* - Employed in acute experiments for the study of drugs affecting blood pressure. - Both anesthetized and spinal preparations are used, the latter being and particularly for the assay of catecholamines - Contractions of the nictitating membrane are recorded for the investigation of ganglionic blocking action of the drugs. *They studied cats through their eyes by observing the ganglionic action (mydriasis).* - *Used for testing **ATROPINE** (cholinergic drug) by induce mydriasis that can be observed through the cat's eyes.* - Also the model of choice for neurological research, as are studies on movement, balance, hearing, and motor neuron studies related to spinal cord injuries. They have been used for mapping trials due to anatomical similarities in brain structure. - Also used as models for viral disease syndromes. 7. **FROG** - Belongs to the class of amphibians. It has been used since 200 years ago. The amphibian animal is safe to handle. It cannot breed in the lab. - *No ethical complication; no need for the veterinarian's permission to test this animal.* - Most commonly used in physiology, pharmacology, and toxicology. The isolated preparation of frogs need not be maintained at 37℃ and the experiments are performed at room temperature. - *[Experimental Use]*: - Study of a drug on the CNS, the study of isolated tissue such as rectus abdominus muscle, heart preparation, drugs acting on CNS, and drugs acting on the neuromuscular junction, as well as to determine the retinal toxicity of the drug. - Human diseases, vertebrate embryology and growth, basic cell and molecular biology, genomics, neurobiology, and toxicology are all studied and modeled using *[Xenopus Laevis]* (African Frog). Xenopus eggs and embryos have several characteristics that make them an excellent tool for biomedical research. 8. **DOG** - One of the reasons being that dogs are physiologically quite similar to humans, they also have roughly the same number of genes as humans, and their genome has been sequenced. This makes dogs particularly useful in genetic studies. - Dogs are also known to suffer from diseases such as diabetes, epilepsy, autoimmune diseases, cancers, and eye diseases that are similar to human diseases. - ***Beagles:** most common breed of dog used for experiment because they are docile and small (Google.com)* - *[Experimental Uses]*: - Acute experiment for medication affecting blood pressure and intestinal movement, gastric acid secretion research, antidiabetic agent study, and pharmacokinetic study. - *Test for Diabetes and Epilepsy* 9. **MONKEYS** - Both structurally and functionally monkeys and apes **closely resemble man**. They are used in relatively limited numbers, but they\'ve played a role in a variety of big medical breakthroughs, including the polio vaccine, premature baby life support systems, and deep brain stimulation for Parkinsonism. - *[Experimental Use]:* - Primates are used in the field of virology, parasitology, immunology, nutrition, reproduction, etc. Primate research is currently focused on infectious diseases, such as developing vaccines and therapies for HIV/AIDS. - They are also used in modern drugs and vaccines for safety research. ***(Polio vaccine)*** **OTHER ANIMAL USED FOR TESTING** - **PIGEON:** used for anti-arrhythmic research; induce **DIGOXIN;** Mnemonic: **[PIGOXIN]** **PRECLINICAL RESEARCH** - Usually, preclinical studies are not very large. However, these studies must provide detailed information on dosing and toxicity levels. - After preclinical testing, researchers review their findings and decide whether the drug should be tested in people. **FOUR (4) Rs IN ANIMAL ETHICS** 1. **REPLACEMENT** - The substitution for conscious living higher animals of insentient material; alternative for animals. - Using in vitro testing so that no living things will be harmed. 2. **REDUCTION** - Any strategy that will result in fewer animals is being used in research; *mas konting animals ang gagamitin sa testing para konting gastos o konti lang ang mapapahamak na hayop.* 3. **REFINEMENT** - Modifications of experimental procedures to minimize pain and trauma to animals; *Dapat magaganda at appropriate ang mga equipments na gagamitin sa animal testing.* 4. **REHABILITATION** - A treatment or treatments designed to facilitate the process of recovery from injury, illness, or a disease to as a condition as possible; *pag revive sa animal; Goal: to bring the animal BACK TO NORMAL.* *Reference: Slideshare.com* **STEP 3: CLINICAL RESEARCH** - While preclinical research answers basic questions about a drug's safety, it is not a substitute for studies of ways the drug will interact with the human body - Refers to studies, or trials, that are done in people. - As the developers design the clinical study, they will consider what they want to accomplish for each of the different Clinical Research Phases and begin the Investigational New Drug Process (IND), a process they must go through before clinical research begins. **DESIGNING CLINICAL TRIALS** - Researchers design clinical trials to answer specific research questions related to a medical product. These trials follow a specific study plan, called a protocol, that is developed by the researcher or manufacturer. Before a clinical trial begins, researchers review prior information about the drug to develop research questions and objectives. Then, they decide: - - - - - - - **THE INVESTIGATIONAL NEW DRUG PROCESS** - Drug developers, or sponsors, must submit an Investigational New Drug (IND) application to FDA before beginning clinical research. - In the IND application, developers must include: - Animal study data and toxicity (side effects that cause great harm) data - Manufacturing information - Clinical protocols (study plans) for studies to be conducted - Data from any prior human research - Information about the investigator **CLINICAL RESEARCH PHASE STUDIES** **[PHASE 1]** - **Participants**: 20 to 100 healthy volunteers or people with the disease/condition - **Length of Study**: Several Months - **Purpose**: Safety and Dosage - Approximately 70% of drugs move to the next phase. - Researchers test a new drug in normal volunteers (healthy people). In most cases, 20 to 80 healthy volunteers or people with the disease/condition participate in Phase 1. However, if a new drug is intended for use in cancer patients, researchers conduct Phase 1 studies in patients with that type of cancer. - Studies are closely monitored and gather information about how a drug interacts with the human body. Researchers adjust dosing schemes based on animal data to find out how much of a drug the body can tolerate and what its acute side effects are. - As a Phase 1 trial continues, researchers answer research questions related to how it works in the body, the side effects associated with increased dosage, and early information about how effective it is to determine how best to administer the drug to limit risks and maximize possible benefits. This is important to the design of Phase 2 studies. - **Study Participants**: Up to several hundred people with the disease/condition. - **Length of Study**: Several months to 2 years - **Purpose**: Efficacy and Side Effects - Approximately 33% of drugs move to the next phase - Researchers administer the drug to a group of patients with the disease or condition for which the drug is being developed. Typically involving a few hundred patients, these studies aren\'t large enough to show whether the drug will be beneficial. - Instead, Phase 2 studies provide researchers with additional safety data. Researchers use these data to refine research questions, develop research methods, and design new Phase 3 research protocols. - **Study Participants:** 300 to 3,000 volunteers who have the disease or condition - **Length of the Study:** 1-4 years - **Purpose:** Efficacy and Monitoring of Adverse Reactions - Approximately 25-30% of drugs move to the next phase. - Researchers design Phase 3 studies to demonstrate whether or not a product offers a treatment benefit to a specific population. Sometimes known as pivotal studies, these studies involve 300 to 3,000 participants. - Phase 3 studies provide most of the safety data. In previous studies, it is possible that less common side effects might have gone undetected. Because these studies are larger and longer in duration, the results are more likely to show long-term or rare side effects - Researchers design Phase 3 studies to demonstrate whether or not a product offers a treatment benefit to a specific population. Sometimes known as pivotal studies, these studies involve 300 to 3,000 participants. - Phase 3 studies provide most of the safety data. In previous studies, it is possible that less common side effects might have gone undetected. Because these studies are larger and longer in duration, the results are more likely to show long-term or rare side effects. - **Study Participants:** Several thousand volunteers who have the disease/condition - **Purpose:** Safety and Efficacy - Phase 4 trials are carried out once the drug or device has been approved by FDA during the Post-Market Safety Monitoring. **STEP 4: FDA DRUG REVIEW** - If a drug developer has evidence from its early tests and preclinical and clinical research that a drug is safe and effective for its intended use, the company can file an application to market the drug. The FDA review team thoroughly examines all submitted data on the drug and makes a decision to approve or not to approve it. **NEW DRUG APPLICATION (NDA)** - It tells the full story of a drug. Its purpose is to demonstrate that a drug is safe and effective for its intended use in the population studied. - A drug developer must include everything about a drug---from preclinical data to Phase 3 trial data---in an NDA. Developers must include reports on all studies, data, and analyses. Along with clinical results, developers must include: - Proposed labeling - Safety updates - Drug abuse information - Patent information - Any data from studies that may have been conducted outside the United States - Institutional review board compliance information - Directions for use **FDA REVIEW** - Once FDA receives an NDA, the review team decides if it is complete. If it is not complete, the review team can refuse to file the NDA. If it is complete, the review team has 6 to 10 months to make a decision on whether to approve the drug. The process includes the following: 1. Each member of the review team conducts a full review of his or her section of the application. For example, the medical officer and the statistician review clinical data, while a pharmacologist reviews the data from animal studies. Within each technical discipline represented on the team, there is also a supervisory review. 2. FDA inspectors travel to clinical study sites to conduct a routine inspection. The Agency looks for evidence of fabrication, manipulation, or withholding of data. 3. The project manager assembles all individual reviews and other documents, such as the inspection report, into an "action package." This document becomes the record for FDA review. The review team issues a recommendation, and a senior FDA official makes a decision. **[FDA Approval]** - In cases where FDA determines that a drug has been shown to be safe and effective for its intended use, it is then necessary to work with the applicant to develop and refine prescribing information. This is referred to as "labeling." Labeling accurately and objectively describes the basis for approval and how best to use the drug. - Often, though, remaining issues need to be resolved before the drug can be approved for marketing. Sometimes FDA requires the developer to address questions based on existing data. In other cases, FDA requires additional studies. At this point, the developer can decide whether or not to continue further development. If a developer disagrees with an FDA decision, there are mechanisms for formal appeal. **[FDA Advisory Committee]** - Often, the NDA contains sufficient data for FDA to determine the safety and effectiveness of a drug. Sometimes, though, questions arise that require additional consideration. In these cases, FDA may organize a meeting of one of its Advisory Committees to get independent, expert advice and to permit the public to make comments. These Advisory Committees include a Patient Representative that provides input from the patient perspective. **STEP 5: FDA POST-MARKET DRUG SAFETY MONITORING** - Despite the rigorous steps in the process of drug development, limitations exist. - Therefore, the true picture of a product's safety actually evolves over the months and even years that make up a product's lifetime in the marketplace. FDA reviews report of problems with prescription and over-the-counter drugs, and can decide to add cautions to the dosage or usage information, as well as other measures for more serious issues. **[Supplemental Applications]** - **[INDs for Marketed Drugs]** - **[Manufacturer Inspections]** - **[Drug Advertising]** - - - **[Generic Drugs]** - New drugs are patent protected when they are approved for marketing. This means that only the sponsor has the right to market the drug exclusively. Once the patent expires, other drug manufacturers can develop the drug, which will be known as a generic version of the drug. Generic drugs are comparable to brand name drugs and must have the same: - - - - - - - Generic drug manufacturers do not have to conduct clinical trials to demonstrate that their product is safe and effective. Instead, they conduct bio-equivalence studies and file an Abbreviated New Drug Application. - *Generic drugs are patented in **20 years.** After 20 years, you can manufacture another brand name from this generic drug.* **ANESTHESIA** - **Anesthesia --** numbness; associated to the feeling of pain - **Analgesia --** subcategory of anesthesia: non-pain **GENERAL ANESTHESIA** - Is used to put a patient in a state of reversible and controlled unconsciousness; used in operations or surgery. - Upon induction, the patient will undergo - Amnesia - Analgesia - Skeletal Muscle Paralysis - Sedation **INHALED** 1. **Nitrous Oxide** - First general anesthesia - Laughing gas - Abuse potential - No metabolism - No pain - *Due to its abused potential, it is not widely use.* 2. **Chlorofluorocarbons** - Malignant Hypertension - Very Pungent - Can cause Respiratory Irritation - Least likely with Sevoflurane - Most likely with Desflurane - *Solution: **Opiates** -- lowers respiratory irritation* **INTRAVENOUS** - **Propofol** -- May cause type B acidosis - **Barbiturates** -- Thiopental, Methohexital - **Ketamine** - **Etomidate** - **Opioids** **Preparation of Patients before Induction:** - **Midazolam (Benzodiazepines)** - Calms down patient - **Dexmedetomidine (Alpha 2- Agonist)** - Sedate the subject - **Atropine (Antimuscarinic agent)** - To dry out secretions - **Neuromuscular blockers (NMBs) + General anesthesia** **STAGES OF ANESTHESIA** Phases: - Induction (*Patulugin ang pasyente*) - Maintenance (*managed by an anesthesiologist; Sedation; experiencing amnesia to maintain sleep*) - Emergence **STAGE 1** - Occurs between Induction and loss of consciousness - Analgesia - Amnesia - Euphoria (overexcitement) **STAGE 2** - **Hyperexcitable Stage** - Occurs between Loss of Consciousness and Regain of Autonomic Stability - The body will temporarily lose the ability to maintain - Temperature - Blood Pressure - Regular Breathing - *Body systems panic and it only happens within seconds.* - The patient may experience: - Excitement - Combative Behavior **STAGE 3** - Occurs between Normal autonomics and Drug Overdose - **Desirable stage** - What GA wants - Unconsciousness - Regular Breathing - Decrease in eye movement - *Returns the body to normal autonomics and the patient is stable and at rest* **4 Planes of Stage 3:** 1. Eye rolling Fix 2. Loss of Corneal and Laryngeal Reflexes 3. Pupils dilate 4. Intercostal Paralysis - short shallow abdominal respiration **STAGE 4** - Overdose/ Toxicity - Medullary Depression -- depression of the organs - Decrease breathing - Autonomic Stability **STAGE 5** - Respiratory Arrest - Cardiac Depression and arrest - No eye movement - Death **MINIMUM ALVEOLAR CONCENTRATION** - Concentration of gas in the lungs capable of preventing movement in 50% of subjects in response to pain or a surgical stimulus - Analogous to ED50 (Effective Dose of 50%) - MAC and Potency is **inversely proportional.** **BLOOD GAS PARTITION COEFFICIENT** - Measure of the solubility of anesthetic in the blood - BGPC is **directly proportional** to Inhaled anesthetic dissolved in blood - Increase solubility, increase time for the anesthetic to cross BBB - Decrease BGPC - Rapid Onset - Rapid Recovery from Anesthesia - **↑ BGPC = ↑ Blood** - *Then, it will contain water that is why cells cannot absorb too much of the drug.* - *These must be the standards when entering the BBB:* - **L =** Lipophilic - **U =** Unionized - **N =** Non-polar - **A =** Absorbed - **↑ Potency = ↓ MAC** **Inhaled GA** **MAC** **BGPC** ------------------------ --------- -------------------- **Nitrous oxide** 105 % 0.45 **Chlorofluorocarbon** 1-6 % 0.45 (Desflurane) 1.4 % (Isoflurane) - **Nitrous oxide = ↓ Potency** - **Chlorofluorocarbon = ↑ Potency** **LOCAL ANESTHETICS** - Inhibits voltage gated Na+ Channels - (-) Conduction of action potential - *Dapat negative ang loob ng cells para relax ang katawan ng pasyente after mabigyan ng LA.* - *It only numbs a certain site of the body unlike GA that affects the whole system.* - Cocaine -- First local anesthetics - Esters - Amides **3 STEP PROCESS OF LOCAL ANESTHETICS** 1. Cross Cell Membrane 2. Inside the cell, Binds w/ Na+ Channel 3. After binding w/ Na+ Channel - Stabilize the inactivated states of NA+ Channels **NOTES** - Cocaine is not used for local anesthetics anymore. - Cocaine does not require epinephrine, why? - *It has intrinsic (-) NE reuptake and sympathomimetic action.* - We don't use benzocaine too much anymore, why? - It is water soluble and cannot be fully metabolized. **ALTERNATIVES TO ANIMAL EXPERIMENTATION** - **Zebrafish** - This fish has a high breeding rate since a single couple can produce more than 200 larvae under ideal conditions and 70% of its genome is similar to the human genome. - Unlike mammals, the Zebrafish has a significant capacity for **neuronal regeneration**, which favors the study of mechanisms associated with **cell regeneration** after neuron damage. - It also possesses a very special ability. They can **repair damaged heat muscle** after various types of heart injury. - Due to its well-defined behaviors, it can be used for modeling alcohol intoxication, stress, anxiety, and even depression. - Moreover, the zebrafish can be used in toxicology, biochemistry, and behavioral neuroscience. - It is used in Replacement method to regulate the use of mice or rats. - ***Caenorhabditis elegans* (Worm)** - These worms are smaller than 1 mm and transparent, which facilitates maintenance and microscopic analysis. - 80% of their genome is similar to that of humans. - Genetic manipulation of the worm is relatively simple. - Worms can be used to study ways to decrease or even eliminate expression of the **beta-amyloid protein**, one of the proteins linked to **Alzheimer\'s disease.** - It is also used as an animal experiment replacement for assessing the virulence of different Salmonella enterica strains. - It has become a popular toxicological and biological test organism in the last two decades. - ***Drosophila melanogaster* (Fruit fly)** - These flies have well-developed reproduction parameters and are easy to handle, with 60% to 80% of their genome similar to that of humans. - Fruit flies' chromosomes are arranged in what scientists call **polytene chromosomes** and these appear like barcodes because they have a repeated pattern of light and dark bands. The dark bands are formed of densely packed chromatin and the lighter bands are formed of moderately packed chromatin. - They are bred in glass containers and kept at a temperature between 20 and 24 degrees. - They feed on maize meal and live for about 60 days, so they can be used in analyses of their full life cycle, from the larval to the adult stage of life. - The importance of fruit flies as an animal model was realized by Thomas Hunt Morgan, who was awarded the 1933 Nobel Prize for physiology or medicine after demonstrating that genetic information is carried on chromosomes. - Its importance of human health was recognized more recently by the award of the Nobel prize for medicine in 1995, for work on the genetic control of early embryonic development. - Research on neurological and metabolic diseases, such as Parkinson's, Alzheimer's and diabetes can be done using these organisms. - These flies helped in the development of drugs to combat pathogens responsible for a range of diseases from skin infections to pneumonia and meningitis. - Recent research with fruit flies has focused on the pathology of Alzheimer's disease, for although the flies have a very simple brain, they have highly developed muscles and nerves. - **Tunicates (Ascidians or Sea Squirts)** - These are invertebrate chordates and prolific producers of a wide variety of biologically active secondary metabolites from cyclic peptides to aromatic alkaloids. - They have toxins that affect DNA transcription, protein translation, drug efflux pumps, signaling pathways and the cytoskeleton. - Two ascidian compounds have already found applications in the treatment of cancer and others are being investigated for their potential in cancer, neurogenerative and other diseases. - One of the most famous drugs derived from tunicates is **Trabectedin (Yondelis)**, an anti-cancer compound initially isolated from the Caribbean tunicate *Ecteinascidia turbinate.* This drug has been used to treat soft tissue sarcoma and ovarian cancer. - **Starfish** - Starfish are valuable in drug discovery due to their bioactive compounds, particularly polar steroids, triterpene glycosides, and lipids, which show potential for pharmaceutical applications. - These compounds exhibit anti-cancer, anti-inflammatory, and antimicrobial properties. For example, starfish-derived steroids have shown promising activity in curbing cancer cell growth without harming healthy cells. - Starfish extracts have also been used in traditional medicine to treat ulcers (Peptic ulcers) and improve digestion, and ongoing research continues to explore their therapeutic potential.