Objective Capital Precious Metals, Diamonds and Gemstones Investment Summit
Metals in Medicine - PGMs in anti-cancer treatments
20 May 2010
by Prof Peter Sadler - University of Warwick
This document discusses the prospects and constraints of using botanical pesticides in pest management. It notes that the global biopesticide market is growing significantly faster than the overall pesticide market. While botanical pesticides have advantages like being indigenous, biodegradable and having less harmful effects than synthetic pesticides, they also have drawbacks like being specific to location/target/conditions and having issues with stability, yields and commercialization. The document outlines various criteria for selecting suitable plant parts for pesticides. It also discusses challenges and opportunities in commercializing botanical pesticides, including issues around quality control, registration requirements, intellectual property rights, and potential solutions involving biotechnology, raising plant tolerance and improving production.
ETS transcription factors bind DNA in a sequence-specific manner through direct contacts between the protein and DNA bases, as well as indirect contacts involving protein-phosphate and protein-water-base interactions. Biochemical footprinting experiments demonstrate specific protection of bases by ETS proteins in high-affinity sequences but not low-affinity sequences. Circular permutation and DNA bending assays further show that ETS binding induces local DNA bending and conformational changes in the bound region.
Cisplatin is a chemotherapy drug discovered in 1965 by Barnett Rosenberg. It was found to inhibit cell division in E. coli bacteria when exposed to an electrical current passing through a platinum electrode in a solution. Further testing showed it could cure mice of cancerous tumors. It is now used to treat several types of cancer through mechanisms where it binds to and crosslinks DNA, preventing cell division. While effective, it has side effects of nephrotoxicity, neurotoxicity, and nausea. Researchers continue working to develop platinum-based drugs with improved toxicity profiles and effectiveness against cisplatin-resistant cancers.
The document discusses the classification, composition, properties and history of precious metal alloys used in dentistry. It covers noble metals like gold, platinum, palladium and their alloys. It describes how these alloys are classified based on their noble metal content and properties. The various heat treatments used to alter the properties of gold alloys are also summarized. Important alloys used for metal-ceramic restorations and their typical compositions are highlighted.
Objective Capital Precious Metals, Diamonds and Gemstones Investment Summit
Metals in Medicine - PGMs in anti-cancer treatments
20 May 2010
by Prof Peter Sadler - University of Warwick
This document summarizes research on using porphyrin nanostructures for artificial photosynthesis applications. Key points include:
- Porphyrin nanotubes and "micro-clovers" self-assemble from ionic interactions between positively and negatively charged porphyrins.
- The nanostructures exhibit light harvesting properties and can generate hydrogen when combined with platinum nanoparticles and an electron donor/acceptor system.
- The morphology of the porphyrin structures can be tuned by varying growth conditions like ionic strength and temperature.
- The researchers propose hybrid artificial photosynthesis systems that combine porphyrin nanostructures with semiconductor nanoparticles to more efficiently split water and generate solar fuels using visible light
The invention of sprycel from benchtop to bedside (Gengcheng Jack Yang)Jack Gengcheng YANG
1) The document describes the discovery and optimization of dasatinib (BMS-354825), a potent pan-Src kinase inhibitor. Initial screening identified a thiazole-based hit that inhibited Lck kinase. Extensive SAR explored substituents on the thiazole ring as well as replacements for the amide linker.
2) Replacing the amide with a 2-aminopyrimidine improved potency against Lck and cellular assays. Further appending a polar side chain to this analog enhanced aqueous solubility and potency, yielding dasatinib.
3) Dasatinib was found to be a highly potent, selective, ATP-competitive inhibitor of Src family kinases and
This document discusses the prospects and constraints of using botanical pesticides in pest management. It notes that the global biopesticide market is growing significantly faster than the overall pesticide market. While botanical pesticides have advantages like being indigenous, biodegradable and having less harmful effects than synthetic pesticides, they also have drawbacks like being specific to location/target/conditions and having issues with stability, yields and commercialization. The document outlines various criteria for selecting suitable plant parts for pesticides. It also discusses challenges and opportunities in commercializing botanical pesticides, including issues around quality control, registration requirements, intellectual property rights, and potential solutions involving biotechnology, raising plant tolerance and improving production.
ETS transcription factors bind DNA in a sequence-specific manner through direct contacts between the protein and DNA bases, as well as indirect contacts involving protein-phosphate and protein-water-base interactions. Biochemical footprinting experiments demonstrate specific protection of bases by ETS proteins in high-affinity sequences but not low-affinity sequences. Circular permutation and DNA bending assays further show that ETS binding induces local DNA bending and conformational changes in the bound region.
Cisplatin is a chemotherapy drug discovered in 1965 by Barnett Rosenberg. It was found to inhibit cell division in E. coli bacteria when exposed to an electrical current passing through a platinum electrode in a solution. Further testing showed it could cure mice of cancerous tumors. It is now used to treat several types of cancer through mechanisms where it binds to and crosslinks DNA, preventing cell division. While effective, it has side effects of nephrotoxicity, neurotoxicity, and nausea. Researchers continue working to develop platinum-based drugs with improved toxicity profiles and effectiveness against cisplatin-resistant cancers.
The document discusses the classification, composition, properties and history of precious metal alloys used in dentistry. It covers noble metals like gold, platinum, palladium and their alloys. It describes how these alloys are classified based on their noble metal content and properties. The various heat treatments used to alter the properties of gold alloys are also summarized. Important alloys used for metal-ceramic restorations and their typical compositions are highlighted.
Objective Capital Precious Metals, Diamonds and Gemstones Investment Summit
Metals in Medicine - PGMs in anti-cancer treatments
20 May 2010
by Prof Peter Sadler - University of Warwick
This document summarizes research on using porphyrin nanostructures for artificial photosynthesis applications. Key points include:
- Porphyrin nanotubes and "micro-clovers" self-assemble from ionic interactions between positively and negatively charged porphyrins.
- The nanostructures exhibit light harvesting properties and can generate hydrogen when combined with platinum nanoparticles and an electron donor/acceptor system.
- The morphology of the porphyrin structures can be tuned by varying growth conditions like ionic strength and temperature.
- The researchers propose hybrid artificial photosynthesis systems that combine porphyrin nanostructures with semiconductor nanoparticles to more efficiently split water and generate solar fuels using visible light
The invention of sprycel from benchtop to bedside (Gengcheng Jack Yang)Jack Gengcheng YANG
1) The document describes the discovery and optimization of dasatinib (BMS-354825), a potent pan-Src kinase inhibitor. Initial screening identified a thiazole-based hit that inhibited Lck kinase. Extensive SAR explored substituents on the thiazole ring as well as replacements for the amide linker.
2) Replacing the amide with a 2-aminopyrimidine improved potency against Lck and cellular assays. Further appending a polar side chain to this analog enhanced aqueous solubility and potency, yielding dasatinib.
3) Dasatinib was found to be a highly potent, selective, ATP-competitive inhibitor of Src family kinases and
Soléo Organics and McArthur Skincare are introducing a new 100% natural sunscreen with no chemical UV absorbers, preservatives, or fragrances. It offers SPF 30+ protection along with water resistance and anti-aging benefits. The formula uses only zinc oxide and organic ingredients and has a 2-year shelf life without preservatives. It is suitable for sensitive skin and the whole family. McArthur Skincare produces therapeutic creams with high concentrations of pawpaw extract to treat conditions like psoriasis, eczema, and joint pain. Customer testimonials praise the products for their skin healing and anti-aging effects.
Organto Foods aims to become a leading organic brand by vertically integrating organic vegetable and fruit farming, processing, and distribution. It currently operates in Canada, Guatemala, Argentina, the US, and the Netherlands. While facing uncertainties, management believes organic food demand will grow significantly and Organto is well-positioned to expand its land, facilities, and product lines to capitalize on this opportunity.
The document discusses GoviEx Uranium Inc., a uranium mining company with projects in Niger. It summarizes GoviEx's milestones since 2007 including exploration programs, resource estimates, development plans, and strategic partnerships. It highlights the opportunity in Niger's uranium industry given the country's role as a top uranium producer. It also notes GoviEx's local investment and community initiatives in Niger. Charts show GoviEx's Madaouela project resources and development plan economics compare favorably to peers given its large resource base and low costs.
This presentation by KBL Mining Limited provides an overview of the company's mining operations and growth strategy. KBL operates the producing Mineral Hill mine in Australia and owns the large undeveloped Sorby Hills project. The presentation outlines a three phase strategy to first improve cash flow at Mineral Hill, then expand margins, and finally diversify revenue through developing Sorby Hills and expanding production at Mineral Hill through exploration. Near term plans at Mineral Hill involve open pit mining the high grade Pearse gold deposit and expanding processing capacity through adding gold and zinc circuits. Sorby Hills is a large undeveloped silver-lead-zinc project that could provide a multi-decade mine life.
$11.00
$3.00
$4.00
$5.00
$2.00
$37.80
Total Operating Cost
$62.80
Capital Cost (Note 2)
$Million
Mine Equipment
Crushing & Screening Plant
Rail Infrastructure
Rail Yard
General Infrastructure
Contingency
$15.0
$15.0
$30.0
$10.0
$15.0
$11.6
Total Capital Cost
$96.6
Century Iron Mines Corporation
1) Century Iron Mines Corporation presented information on its iron ore projects and financial
Canoel International Energy is an oil and gas company traded on the TSX Venture Exchange. It has producing assets in Argentina and Italy, with over 1.6 million barrels of proved reserves according to an independent evaluation. Management is focused on growing production and reserves through development and exploration of its existing assets. It also aims to acquire additional producing assets in emerging markets. Recent developments include negotiations to acquire shut-in production of 7,000-12,000 barrels of oil per day in Libya.
Century Iron Mines Corporation is one of the largest iron ore resource developers in Canada, with over 20 billion tonnes of resources under management across multiple projects. The company is pursuing a strategy of progressively developing these resources, starting with the near-term Joyce Lake direct shipping ore (DSO) deposit. A preliminary economic assessment estimates the Joyce Lake project could have a pre-tax net present value of $95 million and produce 2 million tonnes per year of high-grade DSO at a cash cost of $62.80 per tonne. Century Iron is also exploring additional DSO targets along trend from Joyce Lake to support future expansion.
Century Iron Mines Corporation | Corporate Presentation | November 2012
Speaker: Sandy Chim, C.A., Director, President and Chief Executive Officer
Company Information:
as of Nov 2012
TSX Venture: FER
52-Week high/low: C$0.92-C$2.50
Market Cap: C$97.0m
Recent Price: C$1.02
Shares: 94.9 million
Fully Diluted: 103.8 million
Website: www.centuryiron.com
Century Iron is Canada’s largest holder of iron ore land claims in a public company, with interests in several properties in the Provinces of Quebec and Newfoundland & Labrador. Century’s vision is to exploit its large property asset base to become one of the country’s largest iron ore producers.
Century has structured a unique strategic formula to pave the way to achieving its vision: It has attracted
WISCO and MinMetals, two of the largest Chinese state-owned enterprises, as equity investors and strategic partners (25% and 5% respectively). WISCO is a further 40% JV investor in individual projects, and these partners have committed to 60‑70% off-take agreements for future product. They will also procure to provide up to 70% of production capex on positive feasibility, in the form of nondilutive debt financing for the Canadian company.
Objective Capital's Industrial Minerals & Metals Resources Investment Forum 2012
Ironmongers' Hall, City of London
6 November 2012
Speaker: Alan Cruickshank, Gensource
Objective Capital's Industrial Minerals & Metals Resources Investment Forum 2012
Ironmongers' Hall, City of London
6 November 2012
Speaker: Catherine Feore, Adroit Resources
Objective Capital's Global Resources Investment Forum 2012
Ironmongers' Hall, City of London
25 September 2012
Speaker: Richard Williams, Helio Resource
Objective Capital's Global Resources Investment Forum 2012
Ironmongers' Hall, City of London
25 September 2012
Speaker: Gary Billingsley, Great Western Minerals
An accounting information system (AIS) refers to tools and systems designed for the collection and display of accounting information so accountants and executives can make informed decisions.
Soléo Organics and McArthur Skincare are introducing a new 100% natural sunscreen with no chemical UV absorbers, preservatives, or fragrances. It offers SPF 30+ protection along with water resistance and anti-aging benefits. The formula uses only zinc oxide and organic ingredients and has a 2-year shelf life without preservatives. It is suitable for sensitive skin and the whole family. McArthur Skincare produces therapeutic creams with high concentrations of pawpaw extract to treat conditions like psoriasis, eczema, and joint pain. Customer testimonials praise the products for their skin healing and anti-aging effects.
Organto Foods aims to become a leading organic brand by vertically integrating organic vegetable and fruit farming, processing, and distribution. It currently operates in Canada, Guatemala, Argentina, the US, and the Netherlands. While facing uncertainties, management believes organic food demand will grow significantly and Organto is well-positioned to expand its land, facilities, and product lines to capitalize on this opportunity.
The document discusses GoviEx Uranium Inc., a uranium mining company with projects in Niger. It summarizes GoviEx's milestones since 2007 including exploration programs, resource estimates, development plans, and strategic partnerships. It highlights the opportunity in Niger's uranium industry given the country's role as a top uranium producer. It also notes GoviEx's local investment and community initiatives in Niger. Charts show GoviEx's Madaouela project resources and development plan economics compare favorably to peers given its large resource base and low costs.
This presentation by KBL Mining Limited provides an overview of the company's mining operations and growth strategy. KBL operates the producing Mineral Hill mine in Australia and owns the large undeveloped Sorby Hills project. The presentation outlines a three phase strategy to first improve cash flow at Mineral Hill, then expand margins, and finally diversify revenue through developing Sorby Hills and expanding production at Mineral Hill through exploration. Near term plans at Mineral Hill involve open pit mining the high grade Pearse gold deposit and expanding processing capacity through adding gold and zinc circuits. Sorby Hills is a large undeveloped silver-lead-zinc project that could provide a multi-decade mine life.
$11.00
$3.00
$4.00
$5.00
$2.00
$37.80
Total Operating Cost
$62.80
Capital Cost (Note 2)
$Million
Mine Equipment
Crushing & Screening Plant
Rail Infrastructure
Rail Yard
General Infrastructure
Contingency
$15.0
$15.0
$30.0
$10.0
$15.0
$11.6
Total Capital Cost
$96.6
Century Iron Mines Corporation
1) Century Iron Mines Corporation presented information on its iron ore projects and financial
Canoel International Energy is an oil and gas company traded on the TSX Venture Exchange. It has producing assets in Argentina and Italy, with over 1.6 million barrels of proved reserves according to an independent evaluation. Management is focused on growing production and reserves through development and exploration of its existing assets. It also aims to acquire additional producing assets in emerging markets. Recent developments include negotiations to acquire shut-in production of 7,000-12,000 barrels of oil per day in Libya.
Century Iron Mines Corporation is one of the largest iron ore resource developers in Canada, with over 20 billion tonnes of resources under management across multiple projects. The company is pursuing a strategy of progressively developing these resources, starting with the near-term Joyce Lake direct shipping ore (DSO) deposit. A preliminary economic assessment estimates the Joyce Lake project could have a pre-tax net present value of $95 million and produce 2 million tonnes per year of high-grade DSO at a cash cost of $62.80 per tonne. Century Iron is also exploring additional DSO targets along trend from Joyce Lake to support future expansion.
Century Iron Mines Corporation | Corporate Presentation | November 2012
Speaker: Sandy Chim, C.A., Director, President and Chief Executive Officer
Company Information:
as of Nov 2012
TSX Venture: FER
52-Week high/low: C$0.92-C$2.50
Market Cap: C$97.0m
Recent Price: C$1.02
Shares: 94.9 million
Fully Diluted: 103.8 million
Website: www.centuryiron.com
Century Iron is Canada’s largest holder of iron ore land claims in a public company, with interests in several properties in the Provinces of Quebec and Newfoundland & Labrador. Century’s vision is to exploit its large property asset base to become one of the country’s largest iron ore producers.
Century has structured a unique strategic formula to pave the way to achieving its vision: It has attracted
WISCO and MinMetals, two of the largest Chinese state-owned enterprises, as equity investors and strategic partners (25% and 5% respectively). WISCO is a further 40% JV investor in individual projects, and these partners have committed to 60‑70% off-take agreements for future product. They will also procure to provide up to 70% of production capex on positive feasibility, in the form of nondilutive debt financing for the Canadian company.
Objective Capital's Industrial Minerals & Metals Resources Investment Forum 2012
Ironmongers' Hall, City of London
6 November 2012
Speaker: Alan Cruickshank, Gensource
Objective Capital's Industrial Minerals & Metals Resources Investment Forum 2012
Ironmongers' Hall, City of London
6 November 2012
Speaker: Catherine Feore, Adroit Resources
Objective Capital's Global Resources Investment Forum 2012
Ironmongers' Hall, City of London
25 September 2012
Speaker: Richard Williams, Helio Resource
Objective Capital's Global Resources Investment Forum 2012
Ironmongers' Hall, City of London
25 September 2012
Speaker: Gary Billingsley, Great Western Minerals
An accounting information system (AIS) refers to tools and systems designed for the collection and display of accounting information so accountants and executives can make informed decisions.
13 Jun 24 ILC Retirement Income Summit - slides.pptxILC- UK
ILC's Retirement Income Summit was hosted by M&G and supported by Canada Life. The event brought together key policymakers, influencers and experts to help identify policy priorities for the next Government and ensure more of us have access to a decent income in retirement.
Contributors included:
Jo Blanden, Professor in Economics, University of Surrey
Clive Bolton, CEO, Life Insurance M&G Plc
Jim Boyd, CEO, Equity Release Council
Molly Broome, Economist, Resolution Foundation
Nida Broughton, Co-Director of Economic Policy, Behavioural Insights Team
Jonathan Cribb, Associate Director and Head of Retirement, Savings, and Ageing, Institute for Fiscal Studies
Joanna Elson CBE, Chief Executive Officer, Independent Age
Tom Evans, Managing Director of Retirement, Canada Life
Steve Groves, Chair, Key Retirement Group
Tish Hanifan, Founder and Joint Chair of the Society of Later life Advisers
Sue Lewis, ILC Trustee
Siobhan Lough, Senior Consultant, Hymans Robertson
Mick McAteer, Co-Director, The Financial Inclusion Centre
Stuart McDonald MBE, Head of Longevity and Democratic Insights, LCP
Anusha Mittal, Managing Director, Individual Life and Pensions, M&G Life
Shelley Morris, Senior Project Manager, Living Pension, Living Wage Foundation
Sarah O'Grady, Journalist
Will Sherlock, Head of External Relations, M&G Plc
Daniela Silcock, Head of Policy Research, Pensions Policy Institute
David Sinclair, Chief Executive, ILC
Jordi Skilbeck, Senior Policy Advisor, Pensions and Lifetime Savings Association
Rt Hon Sir Stephen Timms, former Chair, Work & Pensions Committee
Nigel Waterson, ILC Trustee
Jackie Wells, Strategy and Policy Consultant, ILC Strategic Advisory Board
Falcon stands out as a top-tier P2P Invoice Discounting platform in India, bridging esteemed blue-chip companies and eager investors. Our goal is to transform the investment landscape in India by establishing a comprehensive destination for borrowers and investors with diverse profiles and needs, all while minimizing risk. What sets Falcon apart is the elimination of intermediaries such as commercial banks and depository institutions, allowing investors to enjoy higher yields.
A toxic combination of 15 years of low growth, and four decades of high inequality, has left Britain poorer and falling behind its peers. Productivity growth is weak and public investment is low, while wages today are no higher than they were before the financial crisis. Britain needs a new economic strategy to lift itself out of stagnation.
Scotland is in many ways a microcosm of this challenge. It has become a hub for creative industries, is home to several world-class universities and a thriving community of businesses – strengths that need to be harness and leveraged. But it also has high levels of deprivation, with homelessness reaching a record high and nearly half a million people living in very deep poverty last year. Scotland won’t be truly thriving unless it finds ways to ensure that all its inhabitants benefit from growth and investment. This is the central challenge facing policy makers both in Holyrood and Westminster.
What should a new national economic strategy for Scotland include? What would the pursuit of stronger economic growth mean for local, national and UK-wide policy makers? How will economic change affect the jobs we do, the places we live and the businesses we work for? And what are the prospects for cities like Glasgow, and nations like Scotland, in rising to these challenges?
What Lessons Can New Investors Learn from Newman Leech’s Success?Newman Leech
Newman Leech's success in the real estate industry is based on key lessons and principles, offering practical advice for new investors and serving as a blueprint for building a successful career.
Budgeting as a Control Tool in Government Accounting in Nigeria
Being a Paper Presented at the Nigerian Maritime Administration and Safety Agency (NIMASA) Budget Office Staff at Sojourner Hotel, GRA, Ikeja Lagos on Saturday 8th June, 2024.
Madhya Pradesh, the "Heart of India," boasts a rich tapestry of culture and heritage, from ancient dynasties to modern developments. Explore its land records, historical landmarks, and vibrant traditions. From agricultural expanses to urban growth, Madhya Pradesh offers a unique blend of the ancient and modern.
Dr. Alyce Su Cover Story - China's Investment Leadermsthrill
In World Expo 2010 Shanghai – the most visited Expo in the World History
https://www.britannica.com/event/Expo-Shanghai-2010
China’s official organizer of the Expo, CCPIT (China Council for the Promotion of International Trade https://en.ccpit.org/) has chosen Dr. Alyce Su as the Cover Person with Cover Story, in the Expo’s official magazine distributed throughout the Expo, showcasing China’s New Generation of Leaders to the World.
How to Identify the Best Crypto to Buy Now in 2024.pdfKezex (KZX)
To identify the best crypto to buy in 2024, analyze market trends, assess the project's fundamentals, review the development team and community, monitor adoption rates, and evaluate risk tolerance. Stay updated with news, regulatory changes, and expert opinions to make informed decisions.
Confirmation of Payee (CoP) is a vital security measure adopted by financial institutions and payment service providers. Its core purpose is to confirm that the recipient’s name matches the information provided by the sender during a banking transaction, ensuring that funds are transferred to the correct payment account.
Confirmation of Payee was built to tackle the increasing numbers of APP Fraud and in the landscape of UK banking, the spectre of APP fraud looms large. In 2022, over £1.2 billion was stolen by fraudsters through authorised and unauthorised fraud, equivalent to more than £2,300 every minute. This statistic emphasises the urgent need for robust security measures like CoP. While over £1.2 billion was stolen through fraud in 2022, there was an eight per cent reduction compared to 2021 which highlights the positive outcomes obtained from the implementation of Confirmation of Payee. The number of fraud cases across the UK also decreased by four per cent to nearly three million cases during the same period; latest statistics from UK Finance.
In essence, Confirmation of Payee plays a pivotal role in digital banking, guaranteeing the flawless execution of banking transactions. It stands as a guardian against fraud and misallocation, demonstrating the commitment of financial institutions to safeguard their clients’ assets. The next time you engage in a banking transaction, remember the invaluable role of CoP in ensuring the security of your financial interests.
For more details, you can visit https://technoxander.com.
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This presentation explores the pivotal role of KYC compliance in shaping and enforcing global regulations within the dynamic landscape of cryptocurrencies. Dive into the intricate connection between KYC practices and the evolving legal frameworks governing the crypto industry.
How Poonawalla Fincorp and IndusInd Bank’s Co-Branded RuPay Credit Card Cater...beulahfernandes8
The eLITE RuPay Platinum Credit Card, a strategic collaboration between Poonawalla Fincorp and IndusInd Bank, represents a significant advancement in India's digital financial landscape. Spearheaded by Abhay Bhutada, MD of Poonawalla Fincorp, the card leverages deep customer insights to offer tailored features such as no joining fees, movie ticket offers, and rewards on UPI transactions. IndusInd Bank's solid banking infrastructure and digital integration expertise ensure seamless service delivery in today's fast-paced digital economy. With a focus on meeting the growing demand for digital financial services, the card aims to cater to tech-savvy consumers and differentiate itself through unique features and superior customer service, ultimately poised to make a substantial impact in India's digital financial services space.
Discover the Future of Dogecoin with Our Comprehensive Guidance36 Crypto
Learn in-depth about Dogecoin's trajectory and stay informed with 36crypto's essential and up-to-date information about the crypto space.
Our presentation delves into Dogecoin's potential future, exploring whether it's destined to skyrocket to the moon or face a downward spiral. In addition, it highlights invaluable insights. Don't miss out on this opportunity to enhance your crypto understanding!
https://36crypto.com/the-future-of-dogecoin-how-high-can-this-cryptocurrency-reach/
Discover the Future of Dogecoin with Our Comprehensive Guidance
Objective Capital Precious Metals, Diamonds and Gemstones Investment Summit: Metals in Medicine - PGMs in anti-cancer treatments - Peter Sadler
1. PRECIOUS METALS,
DIAMONDS & GEMSTONES
INVESTMENT SUMMIT
2.40 – 3.05
Metals in Medicine - PGMs in anti-cancer treatments
Prof Peter Sadler – Professor of Chemistry, University
of Warwick
THE LONDON CHAMBER OF COMMERCE AND INDUSTRY ● THURSDAY, 20 MAY 2010
www.ObjectiveCapitalConferences.com
2. Metals in Medicine -
PGMs in anticancer treatments
Peter J. Sadler FRS
Professor of Chemistry
University of Warwick
3. A Periodic Table
of Medicines He
B
LiLiBe B C Ne
NO F
Mg Al Ar
Ti Cr Fe S Cl
Na
Sc Ti
V
Cr Cu Ga Ge As2O
Al
N
Br Kr
Mn Zn Si P
Rb Sr Y Zr Nb Ru Rh Pd Ag Cd In Sb Te Xe
K Co 67Ga
Ca
Cs Ba La Hf Ta W Re Os Ir Pt Au Hg Tl Pb Bi Se
90Y Mo 99m
Sn Br
Sedoneural
Sr Tc Ag As I
188Re
Cs La Ce153 Nd Gd Sm Eu Gd Tb Dy Ho Er Sb Yb Lu
Sm
Pr 201Tl Tm
Ba
Pt Au Bi 133Xe
La
4. Design of metal compounds as
therapeutic and diagnostic agents
• There is enormous scope for design
• Recent success with platinum shows that it is
not just the metal which is important, but also
the groups (ligands) which are bound to it
• The shape of the complex (metal + ligands) is
also important
• I give examples here of novel anticancer PGM
anticancer complexes which we have designed
recently
5. Metals in Medicine-
PGMs in anticancer treatments
• Excited-state Platinum
• Organo-PGMs
- Ruthenium
- Iridium
- Osmium
6. Prof Peter Sadler’s Group > 30 years experience
Track record of patents/commercial development
includes
• Pt radiosensitization agents
• Gold anticancer compounds
• Photactivated Pt anticancer agents
• Organometallic Ru, Os and Ir anticancer agents
7. Major Unmet Medical Need
• Cytotoxics (drugs that kill cells) market
segment that includes platinum-based
therapeutics excluding monoclonal antibodies
• US $6b (12.5%) of the cancer market in 2006
– Breast, lung, colorectal and ovarian cancers
• 5-year survival rates
– 40-60% for colorectal cancer
– 35-38% ovarian cancer
• No one effective treatment for many cancers
8. Discovery of anticancer activity
of cisplatin
Barnett Rosenberg
1961 Professor of Biophysics
Michigan State University
+ -
Electric field lines Mitotic spindle
for equal and opposite formation
point charges during division of
a eukaryotic cell
Do electric fields affect cell division?
9. Effect of electric fields on cell growth
“Inert” Pt
electrodes
Growth medium
(NH4Cl)
E. coli + cis-[PtCl2(NH3)2]
Electrolysis led to small amounts of cisplatin
Pt compounds in the medium- stops cell division
Cisplatin
approved
by FDA
1978
1844 Peyrone's chloride
11. Carboplatin Picoplatin
FDA Approval Phase III trials
1989 Colorectal Metastatic
Cancer
Structure: Structure:
S.Neidle, I.M. Ismail, P.J. Sadler Y. Chen, Z. Guo,
J. Inorg. Biochem. S. Parsons, P.J. Sadler
1980 13 , 205-212. Chem. Eur. J. 1998, 4, 672-676.
Work carried out in our laboratory on the structures of Pt anticancer drugs
12. Photochemotherapy
Activation by light
Directed therapy
Destroys the cancer cells
Less side-effects
New approach to use of platinum in chemotherapy
13. Photochemotherapy
Laser
Cancer
cell
Drug Activation
Active platinum species generated only in cancer cells-
reduces side-effects on normal tissue
15. Human bladder cancer cells
+100 µM Pt (dark) +100 µM Pt (light)
50 µm 50 µm
Rapid rounding, “ballooning” of cells in light
[Bednarski, Grünert, Zielzki, Wellner, Mackay, Sadler, Chemistry & Biology, 2006, 13, 61-67]
16. Human bladder cancer cells
25 µM 50 µM 100 µM
DAPI Fluorescence: stains duplex DNA
Cell shrinkage, loss of contact,
nuclear packing and loss of nucleus
17. Rh Prices of
2600 platinum
Platinum group metals
group metals
Global Oxaliplatin Pt
$48,000M $1,900M
(2006) (2006)
1610
Carboplatin
$673M
(2004)
Cisplatin
Pd Ir
$100M
Platinum (1999) 483 Os 510
ca. 6%
Ru 380
190
Cancer market Platinum sales
Less expensive PMGs may also be US Dollars per troy
useful as anticancer agents oz (31.1 g) [04/10]
18. Organo-PGMs
‘Piano-stool’ • Seat coated
Complexes with carbon
Ruthenium
• Reactive Osmium Cisplatin
leg(s) Iridium Different shape
19. Ru(II) Arene Anticancer Complexes
R
η6-arene
Tether
Ru Z
X Chelated
Leaving Y Ligand
Group(s)
Yan, Melchart, Habtemariam, Sadler Chem. Commun. 2005, 4764 – 4776
Dougan, Sadler Chimia , 2007, 61, 704-715
20. Tuning the reactivity of osmium complexes
Reaction DNA Dose
(hours) binding% (µM)
5 100 50
4 80 40
Os
Cl O
3 60 30
R N Weak
O Slow Inactive
binding
2 40 20
1 20 10
No activity –
Human ovarian
now move the R group
cancer cells
van Rijt, Peacock, Johnstone, Parsons, Sadler, Inorg. Chem., 2009, 48 , 1753-62
21. Tuning the reactivity of osmium complexes
Reaction DNA Dose
(hours) binding% (µM)
5 100 50
Os 4 80 40
Cl O
N 3 60 30
O Strong
Fast Active
binding
2 40 20
R 1 20 10
Activity of osmium controlled
by the ligands- Human ovarian
new design concepts cancer cells
van Rijt, Peacock, Johnstone, Parsons, Sadler, Inorg. Chem., 2009, 48 , 1753-62
22. Anticancer Organo-PGMs
Novel DNA interactions
The organo coat can insert between DNA bases
23. Organo-osmium in
ovarian cancer cell
New target sites: new mechanism of action
24. Opportunities
• Activity in human cancer cell lines can be
comparable to or better than cisplatin
• Different mechanisms of action :
activity against cisplatin-resistant cells
• Potentially less severe side-effects
• Potential for combination therapy
25. Next Steps
University • Structure-activity relationships
• Mechanism of cancer cell cytotoxicity including cell
uptake
• Activity of lead compounds in well-established
cancer models
Collaboration
Grants for
• Establish a panel of lead compounds for preclinical
development
• Refine panel of compounds
• Initial clinical trials.
License
• Out-license lead with initial preclinical & clinical data
• License is a further collaboration
26. Advances in PGM Anticancer Agents
• Excited-state
Platinum
• Organo-PGMs
Ruthenium
Osmium
Iridium
Opportunities for
• Licensing patents
• Collaboration in pre-clinical development
Contacts:
• Professor Peter Sadler, University of Warwick
• Dr Shum Prakash, Business Development Manager
Warwick Ventures, University House, Kirby Corner Road, Coventry CV4 8UW
Tel: 024 7657 4145 E-mail: s.prakash@warwick.ac.uk
27. Acknowledgements
• University of Warwick • ICT Biosciences, Bradford
• University of Dundee/ • Czech Academy of Science
Ninewells Hospital • Greifswald University
• Warwick Ventures
Editor's Notes
Explain what Cytotoxic means Emphasize major and unmet! Mabs = monoclonal antibodies. Of the cytotoxics market? Here oxaliplatin 1b in 2006, next slide only 1.9M, At the moment the 5 year survival ates. So there is still a major unmet Medical
Cisplatin the first chemotheraputic drugs discovered in the 1960’s is still in use in the clinic and had a sales in 1999 of 100M, second generation platinum drug carboplatin is most commonly used for ovarian and lung cancer , but may be used in the treatment of many other types, and third generation oxaliplatin also called elaxotin is commonly used to treat cancer of the large bowel . Despite of their succes , there are some drawbacks with these platinum drugs. Like nefrotoxicity, hair loss and nausea
At warwick, we look at the rare metal osmium... The osmium compounds have a different shape as the platinum drug and more importantly the osmium compounds are organomettalic . Meaning that the osmium metal is surrounded by organic components, or organically coated if you like, shown here in yellow. These organic components allow for great scope of design. We have been studying these compound for years and we now have knowledge of how we can change their pharmacokinetics using these organic components.
In summary, th elicense opportunity presented to you today is novel osmium compounds.. There is a hughe market oppurtonuity constituting 6 billion dollars and this is about 12% of the global cancer market. Combination therapy with pltinum drugs or other cancer therapies May wish to update this slide also.
We are currently doing these things at the university We are collaborating to get to the stage a company will licence the technology which means we need to get initial in vivo and patient data to be able to license at the first yellow diamond on the earlier graph
So the effort is high and the rewards are high…
Peter sadler, 30 years of experience in developing drugs and was involved in the early work of carboplatin. With me today is shum prakash, wo is from our technology transfer office, warwick ventures. We have the same one here which is where we emphasised your track record before, but I think in your case, you could emphasise your track record at the beginning of the presentation.