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THOMSON REUTERS INTEGRITY SM Leukemia Therapy: Bcr-Abl Kinase Inhibitors: Selective vs Nonselective THOMSON REUTERS INTEGRITY: SUMMARY In this use case, active compounds for Leukemia will be found and filtered by mechanisms of action and organization.

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THOMSON REUTERS INTEGRITYSM

Leukemia Therapy: Bcr-Abl Kinase Inhibitors: Selective vs Nonselective

thomson reuters integrity summary
THOMSON REUTERS INTEGRITY:SUMMARY

In this use case, active compounds for Leukemia will be found and filtered by mechanisms of action and organization.

Comparing two launched products for this condition, Gleevec® and Tasigna®, a structure search will be run to find structure-activity relationships for specific Bcr-Abl kinase inhibitors.

From specific Abl kinase inhibitors list, related targets associated to these drugs will be examined and the targetscape for Acute Myeloiod Leukemia will be explored

thomson reuters integrity leukemia
THOMSON REUTERS INTEGRITY: LEUKEMIA

Leukemia is a malignant disease of the bone marrow and blood that is characterized by the uncontrolled accumulation of white blood cells

About 4,400 people in the U.S. will die of Chronic lymphocytic leukemia during 2009, according to the American Cancer Society. Among patients with Acute lymphocytic leukemia in the U.S., approximately 1,400 are predicted to die during the same year; two-thirds of these would be adults. Approximately 470 people with Chronic myelogenous leukemia and 9,000 with Acute myelogenous leukemia are expected to die as a cause of their disease this year in the U.S.

The treatment of leukemia is complex and is based on a range of factors including characteristics of the disease itself (type of leukemia, extent of disease, whether or not the disease has been treated previously) and patient characteristics (age, symptoms and general health).

Chemotherapy is the primary treatment for acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL), although the specific drugs used to treat each form differ. In some cases radiotherapy or stem cell transplantation may be used in combination with chemotherapy.

thomson reuters integrity drugs biologics knowledge area guided search
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: GUIDED SEARCH

Go to the Drugs & Biologics Knowledge Area from the pull down menu at the left part of the home page of Integrity

thomson reuters integrity drugs biologics knowledge area guided search5
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: GUIDED SEARCH

Click the down arrow to open the pull-down of search fields

and select Development Status -> Condition in this example.

thomson reuters integrity drugs biologics knowledge area guided search6
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: GUIDED SEARCH

Next open the Browse Index of search terms for the search field chosen, run a preliminary lookup search to locate a term in the index, and then click the term on the right to copy it to the Search Form.

thomson reuters integrity drugs biologics knowledge area guided search7
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: GUIDED SEARCH

Add other relevant criteria to the Search Form – in this example, select Development Status -> Under Active Development = Y

Click Start or hit return to launch the search.

thomson reuters integrity drugs biologics knowledge area guided search8
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: GUIDED SEARCH

From the list of active development programs for leukemia, retrieve the corresponding products by selecting the Product List from the Options pull-down menu

thomson reuters integrity drugs biologics knowledge area guided search9
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: GUIDED SEARCH

Use the Filter by Statisticscharts to further limit the search. From the Product List obtained, filter by Organization

thomson reuters integrity drugs biologics knowledge area guided search10
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: GUIDED SEARCH

Check the companies of interest and click View Subset(s)

In this example, select the Novartis and Novartis Oncology checkboxes

thomson reuters integrity drugs biologics knowledge area guided search11
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: GUIDED SEARCH

Select the Full Record option from the Options pull-down menu

thomson reuters integrity drugs biologics knowledge area guided search12
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: GUIDED SEARCH

The product record for Imatinib mesylateshows that it acts onmultiple targets, including Abl KinaseandBcr-Abl Kinase

thomson reuters integrity drugs biologics knowledge area guided search13
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: GUIDED SEARCH

The product record for Nilotinib Hydrochloride Monohydrate shows that it acts selectively on Bcr-Abl Kinase. To further investigate selectivity of similar compounds a substructure search can be run.

thomson reuters integrity drugs biologics knowledge area structure search
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: STRUCTURE SEARCH

To set up a structure search, select a Knowledge Area – Drugs & Biologicsin this example – and click the Structure Search button to go to the Structure Search Form.

thomson reuters integrity drugs biologics knowledge area structure search15
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: STRUCTURE SEARCH

Draw or paste a structure in the structure search window.

thomson reuters integrity drugs biologics knowledge area structure search16
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: STRUCTURE SEARCH

Combine a substructure search with a text search by opening the search field menu and selecting a field - in this example, Therapeutic Group.

Then open the corresponding Browse Index to select a term.

thomson reuters integrity drugs biologics knowledge area structure search17
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: STRUCTURE SEARCH

Use the Lookup box in the Browse Index to locate terms in the hierarchical Therapeutic Group index.

Then click a term -- Oncolytic Drugs in this example -- to copy it to the Search Form.

thomson reuters integrity drugs biologics knowledge area structure search18
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: STRUCTURE SEARCH

Click Start or press Return to launch a search for products with this Therapeutic Groupclassification and that share a similar substructure.

thomson reuters integrity drugs biologics knowledge area structure search19
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: STRUCTURE SEARCH

Compounds can be classified quickly and easily by using Filter by Statistics. In this example, select to filter by Molecular Mechanisms.

thomson reuters integrity drugs biologics knowledge area structure search20
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: STRUCTURE SEARCH

The chart shows that many of the compounds have more than one mechanism of action.

Using the checkbox function, select Bcr-AblKinase Inhibitorsand click View Subset(s) to view the subset of compounds with this mechanism.

thomson reuters integrity drugs biologics knowledge area structure search21
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: STRUCTURE SEARCH

From the original list of product records retrieved that are Oncolytic Drugs and that have a similar structure, these are the compounds that are Bcr-Ablkinase inhibitors. Select the Product List with Structures from the pull-down menu

thomson reuters integrity drugs biologics knowledge area structure search22
THOMSON REUTERS INTEGRITY: DRUGS & BIOLOGICS KNOWLEDGE AREA: STRUCTURE SEARCH

From this list, structure-activity relationships can be examined. Access to Experimental Pharmacology, Pharmacokinetics/ Metabolism and other data can be obtained through the All Related Information via Quick Search

thomson reuters integrity information retrieval via targets pathways
THOMSON REUTERS INTEGRITY: INFORMATION RETRIEVAL VIA TARGETS & PATHWAYS

Select the Targets & Pathways enabled bar

thomson reuters integrity information retrieval via targets pathways24
THOMSON REUTERS INTEGRITY: INFORMATION RETRIEVAL VIA TARGETS & PATHWAYS

From the Targets & Pathways list obtained, select the Targetscapes option

thomson reuters integrity information retrieval via targets pathways25
THOMSON REUTERS INTEGRITY: INFORMATION RETRIEVAL VIA TARGETS & PATHWAYS

Click on the Acute Myeloid Leukemia Targescape…

thomson reuters integrity information retrieval via targets pathways26
THOMSON REUTERS INTEGRITY: INFORMATION RETRIEVAL VIA TARGETS & PATHWAYS

… to view the molecular landscape for this condition.

thomson reuters integrity support help
THOMSON REUTERS INTEGRITY: SUPPORT/HELP

For questions about Integrity’s contents or features, send a message via the Help Request / Suggestion Form in Integrity or contact integritysupport@prous.com