This document provides information about cancer including:
- Cancer is characterized by abnormal, uncontrolled cell growth.
- Lung cancer is the most common cancer in men and breast cancer is most common in women.
- Cancers can be benign or malignant tumors and are classified into broad groups like carcinomas and sarcomas.
- Cancers are caused by physical, biological, chemical and genetic factors like viruses, radiation, and lifestyle habits.
- Diagnosis involves biopsies, imaging tests, and analyzing tumor markers in blood. Staging determines how advanced a cancer is.
- Treatment includes surgery, radiation, immunotherapy, chemotherapy and other drugs that target cell growth pathways.
INTRODUCTION TO MALAREA [ANTI-MALARARIAL DRUGS AND ITS ANALOGUES]Shikha Popali
MALAREA CAUSED DUE TO BITE OF MOSQUITO , HERE IN THIS PRESENTATION THE DRUGS USE TO TREAT MALAREA CALLED ANTIMALARIAL DRUGS ARE DISCUSED WITH ITS ANALOGUES
Anti-Neoplastic agents(Anti-cancer drugs)-History-Mechanism of actions-Classifications,SAR,Synthesis and Uses.(Medicinal chemistry)
P.Ravisankar
Vignan Pharmacy College
Vadlamudi. Guntur-A.P. India.
INTRODUCTION TO MALAREA [ANTI-MALARARIAL DRUGS AND ITS ANALOGUES]Shikha Popali
MALAREA CAUSED DUE TO BITE OF MOSQUITO , HERE IN THIS PRESENTATION THE DRUGS USE TO TREAT MALAREA CALLED ANTIMALARIAL DRUGS ARE DISCUSED WITH ITS ANALOGUES
Anti-Neoplastic agents(Anti-cancer drugs)-History-Mechanism of actions-Classifications,SAR,Synthesis and Uses.(Medicinal chemistry)
P.Ravisankar
Vignan Pharmacy College
Vadlamudi. Guntur-A.P. India.
This PPT covers the Drug therapy for Malaria. This PPT includes Malaria cycle, different types of malaria , classification of antimalarial drugs and pharmacotherapy of all antimalarial drugs
This PPT covers the Drug therapy for Malaria. This PPT includes Malaria cycle, different types of malaria , classification of antimalarial drugs and pharmacotherapy of all antimalarial drugs
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread to other parts of the body.
## To understand how cancer develops and progresses, researchers first need to investigate the biological differences between normal cells and cancer cells. This work focuses on the mechanisms that underlie fundamental processes such as cell growth, the transformation of normal cells to cancer cells, and the spread, or metastasis, of cancer cells.
Diploma nursing Extension student International institute of health science jinja,Uganda presenting the Antineoplastic drugs, the main objectives is
1.definition.
2.classes of Antineoplastic drugs.
3.Different types of drugs in each class.
4Different forms,dosage,indication,Adverse effects of some common Antineoplastic.
Nursing interventions in Antineoplastic drugs.
cancer chemotherapy
Introduction,Types of cancer,Aetiology of cancer,Pathogenesis of cancer,Diagnosis of cancer,Treatment of cancer,Novel drugs for cancer,Future prospects
Introduction, Types, Causes,
Symptoms of cancer
Anti-cancer drug &
Recent advances in cancer treatment included Newer drug carrier systems, Nanotechnology, Carbon nanotubes, Cancer Vaccine, Antigen Vaccines, Dendritic Cell Vaccines, DNA Vaccines.
Cancer is a disease in which some of the body’s cells grow uncontrollably and spread to other parts of the body. Here in this presentation cancer and its characteristics are discussed along with anti-cancer drugs, in brief.
Anticancer drugs: Classification , general toxicity and Alkylating agents.Ameena Kadar
Neoplasm or cancer is one of the dangerous condition. Here we discuss about cancer and it's drug classification, general toxicity and brief description about Alkylating agents.
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
Follow us on: Pinterest
Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
2. CANCER
Cancer is a disease characterized by uncontrollable,
irreversible, independent, autonomous, uncoordinated and
relatively unlimited and abnormal over growth of tissues.
• Currently 1 in 4 deaths in USA are due to cancer.
• 1 in 17 deaths are due to lung cancer.
• An estimated 2,22,520 people diagnosed lung cancer in the
United States in 2010.
• Lung cancer is the most common cancer in men.
• Breast cancer is the most common cancer in women.
• Around 15 lakh new cases are diagnosed every year in
india.
3.
4. Examples of Benign Tumors
• Papilloma - A projecting mass on the skin (for example, a
wart)
• Adenoma - A tumor that grows in and around the glands
• Lipoma - A tumor in fatty tissue
• Osteoma - A tumor originating in the bones
• Myoma - A tumor of muscle tissue
• Angioma - A tumor usually composed of small blood or
lymph vessels
• Nevus - A small skin tumor of one variety of tissues (for
example, a mole).
5. How is cancer classified?
There are five broad groups that are used to classify cancer.
Carcinomas are characterized by cells that cover internal and
external parts of the body such as lung, breast, and colon
cancer.
Sarcomas are characterized by cells that are located in bone,
cartilage, fat, connective tissue, muscle, and other supportive
tissues.
Lymphomas are cancers that begin in the lymph nodes and
immune system tissues.
Leukemias are cancers that begin in the bone marrow and often
accumulate in the blood stream.
Adenomas are cancers that arise in the thyroid, the pituitary
gland, the adrenal gland, and other glandular tissues.
6.
7.
8. CAUSES OF CANCER
There are several agents responsible for cancer. The agents (physical,
chemical and biological) which causes cancer are called carcinogens.
1. Physical agents: Uv and ionizing radiations (x-ray, gamma and
alpha and beta rays cause cancer, uv rays of sunlight, nuclear
fission. These radiations have mutagenic effect. Eg: Leukaemias,
skin, lung, breast, osteosarcoma, thyroid cancer.
2. Biological agents:
a) Bacterial agents: peptic ulcers and chronic gastritis and if these
are left untreated for along time leads to gastric cancer.
b) Fungal agents: The fungus Aspergillus flavus releases aflatoxins
in stored food and grains .If this contaminated food is consumed
(especially by Hepatitis B virus infected patients) it leads to
hepato cellular carcinoma.
c) Viral agents: Cervical cancer, Burkitt’s lymphoma, hairy cell
leukaemia, Hepatic carcinoma.
9. 3. Chemical agents: Alkylating agents, The acylating agents,
Polyaromatic hydrocarbons, Aniline, arsenic, Anthracenes,
dimethylsulphate, diepoxybutane, acetyl imidazole, dimethyl
carbamyl chloride. carcinogens like nicotine, asbestos,
coaltar, benzene, aniline dyes.
4. Genetic factors: Genetic inheritance plays a key role in
causing some of the cancers (breast carcinoma, retino
blastinoma.
5. Diet and habits: People taking rich in fats, low fibre content
and stored grains. Alcoholism, smoking, chewing tobacco and
betel nut.(pan-masala, Gutka)
6. Hormones and Drugs: Taking excessive oestrogens during
the times of pregnancy (Vaginal endometrial cancer is
prevalent in the girls born to the mothers)
10. 7. Epidemiological factors:
a) Geographical and Racial factors : Climate, soil, diet habit
and customs etc. Genetic composition also influence the
variations in cancer. Eg: Breast cancer in prevalent in
American women. Gastric carcinoma is in Japanese.
b) Environmental and cultural factors: Exposure to
industrial contaminants, smoke and radioactive metals.
Cancer of penis is very rare in Muslims and jews due to the
custom of circumcision and their female partners are less
likely to suffer(prone) to cancer of cervix.
c) Age and sex: High risk of cancer is incident at an older age
due to reduction in immunity. It is usually seen in 5th decade
of life. Men are more prone to lung cancer while women are
susceptible to breast cancer.
11. • These are those drugs which are used in the
treatment of cancer, malignancy, tumour,
carcinoma, leukemia or neoplasm.
• Neoplasm refers to a group of disease caused
by several agents via chemical compound,
radiant energy.
12. How is cancer diagnosed and staged?
Common tests include the following:
• Biopsy of the tumor
• Blood tests (which look for chemicals such as tumor markers)
• Bone marrow biopsy (for lymphoma or leukemia)
• Chest x-ray
• Complete blood count (CBC)
• CT scan
• MRI scan (magnetic resonance imaging)
• Extracting cancer cells and looking at them under a
microscope is the only absolute way to diagnose cancer. This
procedure is called a biopsy.
• Physicians will analyze your bodys sugars, fats, proteins, and
DNA at the molecular level.
• For example, cancerous prostate cells release a higher level of
a chemical called PSA (prostate-specific antigen) into the
blood stream that can be detected by a blood test.
13. TREATMENT OF CANCER
Cancer can be treated by the following means:
Surgery Robotic radical prostatectomy for prostate cancer. (3-
D) view of the surgical field, at a greatly increased
magnification, up to 15 times greater than the human eye.
Radiation therapy.
Immunotherapy.
Hormonal therapy.
Antibiotics.
Chemotherapy.
Chemotherapy is the term applied for a wide range of
chemical substances i.e. drugs that are employed in the
treating the cancer.
These drugs may act by various mechanisms like Interfering
with the replication of DNA. Inhibiting the formation of
important molecules which are needed for DNA formation
and inhibiting the mytotic spindle.
18. vi. Platinum containing compounds
Cisplatin Carboplatin
Oxaliplatin
Oxaliplatin is used to
treat colorectal cancer.
19.
20.
21. MOA of Oxaliplatin
After activation, oxaliplatin binds preferentially to the guanine and
cytosine moieties of DNA, leading to cross-linking of DNA, thus
inhibiting DNA synthesis and transcription. Cytotoxicity is cell-cycle
nonspecific.
22. 2. Chain cutters
Calicheamicin γ1
MOA
Calicheamicin γ1 is an anti-tumour agent that was isolated
from a bacterium.
It binds to DNA and is responsible for generating radical
species which lead to the cutting of the DNA chain.
25. MOA:
• The structures of folic acid antagonists and folic
acid are similar
• Folic acid antagonists is actively transported into
mammalian cells and inhibits dihydrofolate
reductase.
• The enzyme that normally converts dietary folate
to the tetrahydrofolate form required for
thymidine and purine synthesis.
26.
27. ii. Pyrimidine antagonists/ Inhibitors of
thymidylate synthase
5-Fluorouracil Ralititrexed
Doxyfluridine
(newer drug of pyrmidine
analogue)
28. MOA:
• Fluorouracil is an analogue of thymine in which
the methyl group is replaced by a fluorine atom.
• It has two active metabolites: 5-FdUMP and 5-
FdUTP. 5-FdUMP inhibits thymidylate synthetases
and prevents the synthesis of thymidine, a major
building block of DNA.
• 5-FdUTP is incorporated into RNA by RNA
polymerase and interferes with RNA function.
29.
30. iii. Purine antagonists
6-Mercaptopurine 6-Thioguanine
MOA:
• 6-Mercaptopurine is an analogue of naturally occurring purine,
which is essential component of DNA called adenine.
• 6-MP inhibit the hypoxanthine-guanine phosphoribosyl
transferase (HGPRT) which converts thioinosine
monophosphate to adenine. Adenine and guanine nucleotides
that are building blocks for RNA and DNA, thus inhibits the
DNA synthesis.
31. iv. Inhibitors of DNA polymereases
Cytarabine Gemcitabine Fludarabine
• DNA polymerases catalyse the synthesis of DNA using the
four deoxyribonucleotide building blocks dATP, dGTP,
dCTP, and dTTP
32. MOA:
• The anticancer drug cytarabine is an analogue of 2′
deoxycytidine and acts as a prodrug.
• It is phosphorylated in cells to the corresponding
triphosphate (ara-CTP) which acts as a competitive
inhibitor. In addition, ara-CTP can act as a substrate
for DNA polymerases and become incorporated into
the growing DNA chain.
• This can lead to chain termination or prevent
replication of the modified DNA.
33.
34. 4. Microtubule Inhibitors
i. Agents which inhibit tubulin polymerization
Vincristine , Vinblastine , Vindesine and Vinorelbine
Vincristine Vinblastine
37. MOA: Microtubule Inhibitors binds to the microtubular
proteins of the mitotic spindle, leading to crystallization of
the microtubule and mitotic arrest or cell death.
eg: Vinnca alkaloids
38. ii. Agents which inhibit tubulin depolymerization
Paclitaxel Docetaxel
41. 5. Inhibitors of signalling pathways
i. Inhibition of farnesyl transferase and Ras protein
Lonafarnib Tipifarnib
MOA: Ras proteins are an inherent component of the
cellular signalling pathways which control cell growth and
multiplication. They are small G-proteins which bind GDP in
resting state and bind GTP in active state.
42. • Binding to GTP is temporary. Because the protein can auto-
catalyse its hydrolysis back to GDP and return to the resting
state.
• Abnormal Ras derives from a mutation of the ras gene to form
a ras oncogene.
• So Mutant Ras proteins persistently bind GTP, however, and
fail to hydrolyse it, such that they are constantly active. Due to
this uncontrolled cell growth and cell division.
• farnesyl transferase is responsible for attaching farnesyl
group to the Ras protein when it is in the cytoplasm of the cell.
• The farnesyl group is hydrophobic and acts as a hook to hold
the Ras protein to the inner surface of the cell membrane. This
is necessary if the Ras protein is to interact with other
elements of the signal transduction process.
43. ii. Protein kinase inhibitors
a) Kinase inhibitors of the epidermal growth factor
receptor (EGF-R)
Gefitinib Erlotinib
44. Lapatinib
MOA of Gefitinib
EGF-R is a membrane-bound tyrosine kinase
receptor.
Gefitinib was found to mimic ATP and bind to the
ATP-binding region of the kinase active site and
inhibit the EGFR signalling pathways
47. b) Kinase inhibitors of the vascular endothelial growth
factor receptor (VEGF-R) or Angiogenesis Inhibitors
Vandetanib Pazopanib
MOA:
• Angiogenesis is the formation of new blood vessels. This
process involves the migration, growth, and differentiation
of endothelial cells
• Angiogenesis plays a critical role in the growth of cancer
because solid tumors need a blood supply.
48.
49. c) Kinase inhibitors of Abelson tyrosine kinase
(BCR-ABL inhibitor)
Imatinib Nilotinib
Dasatinib
50. The Philadelphia chromosome results from a reciprocal translocation
between chromosomes 9 and 22 and generates the Bcr–Abl chimera
protein.
51. MOA :
Imatinib was found to mimic ATP and bind to the
ATP-binding region of the kinase active site and
inhibit the BCR-ABL signalling pathways
52. d) Platelet-derived growth factor receptors (PDGF-R)
Inhibitors
Sunitinib Sorafenib
MOA:
Sorafenib is a protein kinase inhibitor with activity against
many protein kinases, including VEGFR, PDGFR and RAF
kinases.
PDGF plays a role in embryonic development, cell
proliferation, cell migration, and angiogenesis.
53. e) Hedgehog pathway inhibitors
Vismodegib
MOA:
Hedgehog signaling pathway include genes involved
in cell proliferation, apoptosis, angiogenesis, cancer
stem cell maintenance. So Vismodegib inhibits
Hedgehog Signaling pathway.
54. Uses : used in treatment of basal cell carcinoma
SMO : Smoothened receptor
GLI : glioma-associated oncogene
57. Pertuzumab
• Pertuzumab is a monoclonal antibody against
her2 (Human epidermal growth factor
receptor-2) and block ligand-dependent hetero
dimerization of her2 with other her family
members.
58. 8. Hormone-based therapies
8.1. Glucocorticoids, estrogens, progestins, and androgens
a) Glucocorticoids
Prednisolone Prednisone
62. MOA OF FULVESTRANT:
When fulvestrant binds to estrogen receptor
monomers it inhibits receptor dimerization,
activating function 1 (AF1) and AF2 are rendered
inactive, translocation of receptor to the nucleus is
reduced, and degradation of the estrogen receptor is
accelerated.
65. • Nitro group is essential for the activity.
• Aliphatic nitrogen is required for the activity.
• The 2-chloroethyl is the essential group for
activity in carmustine. It is noted that
carmustine is bifunctional, having two 2-
chloroethyl groups.
• Lomustine is monofunctional and has as a
second substituent a cyclohexyl that does not
contribute to its cytotoxic activity but
generates an increase in its half-time.
68. • The importance of C-13 substituted phenyl isoserine side
chain to bioactivity of paclitaxel has been acknowledged for a
long time.
• Replacement of 3’-Ph with other alkyl or alkenyl
substitutions, especially 3'-isobutenyl and 3'- isobutyl groups,
usually improves the activity of paclitaxel analogues.
• Introduction of a fluorine atom to the para position of 3'-
phenyl decreased activity in most cases.
69.
70. SAR of protein kinase C (PKC) inhibitors
phenylaminopyrimidine
71. • A pyridyl group was added at the 3′-position of the
pyrimidine to boost its cellular activity.
• Presence of an amide group was found to confer
inhibitory action against tyrosine kinases.
• Substitution in position 6 of the diamino phenyl ring
abolished the activity against PKC.
• The addition of a methyl group in an ortho position
to the amino group increased selectivity for Bcr-Abl.
• The resulting molecule still showed poor oral
bioavailability and solubility in water, which were
considerably improved by the introduction of an N-
methyl piperazine group.
72. • To abolish its mutagenic potential, the spacer
benzene ring were introduced.
• Nilotinib shows greater
potency and effectiveness
against almost the
totality of resistant ceconferring mutations.
• By inverting the amide linking group, by replacing the
piperazine ring with 3-methylimidazole, and by
adding trifluoro-methyl group to the anilinocarbonyl
substituent to imatinib
structure, give a
potent compound
Nilotinib.
73. SAR OF GEFITINIB (IRESSA)
• Gefitinib comes under the class of kinase
inhibitors of EGF-R. It has been approved for the
treatment of refractory lung cancer.
• It was developed from potent inhibitor.
74. • It had various important features namely a secondary amine,
electron-donating substituents at positions 6 and 7, and a small
lipophilic substituent on the aromatic ring.
• The structure had useful in vitro activity, but its in vivo activity
was hampered by the fact that it was metabolized rapidly by
cytochrome P450 enzymes to give two metabolites.
• The modification of structure was such that both metabolic route
were blocked.
• The methyl group was replaced by a chloro substituent , results in
resistant to oxidation.
• A fluoro substituent was used to block oxidation of the aromatic
para -position.
Metabolically blocked compound
75. • (IC 50 9 nM) was less active in vitro as an enzyme
inhibitor, it showed better in vivo activity.
• Modifications were then carried out to optimize the
pharmacokinetic properties of the drug. A variety of
alkoxy substituents at the 6-position were tried,
culminating in the discovery of gefitinib.
• This contains a morpholine ring, which is often Introduced
to enhance water solubility.
Gefitinib
76. SAR OF CYCLOPHOSPHAMIDE
• BIS-2 CHLOROETHYLAMINO GROUP IS ESSENTIAL
• CHLORO ATOM PROVIDES MAXIMUM ACTIVITY
• LEVO-ISOMER IS INACTIVE
• TRIETHYLENE DERIVATIVE IS INACTIVE
CYCLOPHOSPHAMIDE
77. SAR OF TIPIFARNIB
• TIPIFARNIB belong to the
non-peptide farnesyl
transferase inhibitor.
• The imidazole ring and
quinolone ring both are
important for the activity.
• The imidazole ring acts as a
ligand for the zinc cofactor in
the enzyme's active site.
• The introduction of a meta-
chloro substituent in parent
compound give the compound
which is more potent.
78. • The introduction of N-
methylation of the quinolone
give more potent compound.
• On altering the position of the
nitrogen on the imidazole ring
give highly potent compound.
• Introduction of a primary
amino group to the linker
carbon of imidazole ring and
quinolone ring gives highly
potent compound named as
tipifarnib.