About the Drug Discovery Guide
MSIP has created the Drug Discovery Guide to help provide an understanding for researchers, who are engaged in a drug discovery program, of the experiments necessary to advance a small molecule drug candidate to a stage that will generate commercial interest. The guide itself is a Microsoft Excel template that can be downloaded on this page (please see link above and at the bottom of this page). There are also 3 examples of how to use the guide given different scenarios of drug development.
The guide is separated into different Sections, where the information requested in each Section (if satisfied by specific calculations or experiments) will make the molecule a stronger drug candidate, thus “de-risking” the candidate that is being developed. It is designed to be flexible, as it is understood that each program will have different issues to address. Researchers can download and edit the form to add or remove different items or experiments to the list depending on the nature of the drug discovery program. Please note that the goal is not to fill out the form completely but to provide enough data to show the compounds that are being developed are viable drug candidate to attract commercial interest.
We strongly encourage that each drug discovery program be a collaboration between investigators who 1) have knowledge and expertise in the biology of the target and 2) with a background in medicinal chemistry. A medicinal chemist can offer invaluable insight about a compound’s synthetic viability as well as the expertise to evaluate the drug-like properties of the compounds in development. We also encourage the use of contract research organizations (CROs) to obtain data related to pharmacokinetics and toxicology because these organizations are efficient and highly experienced in obtaining this type of information for the drug development industry.
For questions on using the Drug Discovery Guide, please contact William Chiang, PhD – Business Development Consultant.
How to Use the Drug Discovery Guide
Drug Discovery Guide
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Use this guide as a resource to answer your questions.
About the Drug Discovery Guide
MSIP has created the Drug Discovery Guide to help provide an understanding for researchers, who are engaged in a drug discovery program, of the experiments necessary to advance a small molecule drug candidate to a stage that will generate commercial interest. The guide itself is a Microsoft Excel template that can be downloaded on this page (please see link above and at the bottom of this page). There are also 3 examples of how to use the guide given different scenarios of drug development.
The guide is separated into different Sections, where the information requested in each Section (if satisfied by specific calculations or experiments) will make the molecule a stronger drug candidate, thus “de-risking” the candidate that is being developed. It is designed to be flexible, as it is understood that each program will have different issues to address. Researchers can download and edit the form to add or remove different items or experiments to the list depending on the nature of the drug discovery program. Please note that the goal is not to fill out the form completely but to provide enough data to show the compounds that are being developed are viable drug candidate to attract commercial interest.
We strongly encourage that each drug discovery program be a collaboration between investigators who 1) have knowledge and expertise in the biology of the target and 2) with a background in medicinal chemistry. A medicinal chemist can offer invaluable insight about a compound’s synthetic viability as well as the expertise to evaluate the drug-like properties of the compounds in development. We also encourage the use of contract research organizations (CROs) to obtain data related to pharmacokinetics and toxicology because these organizations are efficient and highly experienced in obtaining this type of information for the drug development industry.
For questions on using the Drug Discovery Guide, please contact William Chiang, PhD – Business Development Consultant.
How to Use the Drug Discovery Guide
Final Product Profile: The purpose of this section is to direct the researcher to think about the properties of the final product at the beginning stages of the project. This is important because the properties of the final drug will dictate the type of experiments that need performed in the subsequent sections. For example, a drug that is administered orally and taken several times a day must have properties that show it is bioavailable, active, and stable in the body for a prolonged period of time. Some of the experiments listed in Section V address these issues.
Information on the Target: This section is to compile information on the target. Prior to starting a drug discovery project, it is important to know how well the target is validated against a particular indication. It is also very important to know the nature of the assays that are to be used in screening. The assays need to have unambiguous readouts and be performed with the appropriate controls.
Small Molecule Development (Hit-Phase): The objective of this section is to identify a set of compounds that have potency against the target from the results of the in vitro assays (e.g., IC50 or Ki < 10 µM).
Small Molecule Development (Lead-Phase): The lead phase is the most important phase for gaining commercial interest. In contrast to the previous section where the objective is to identify molecules with sufficient potency in several different classes, at Lead Phase, the aim is to advance and refine compounds from the Hit Phase to where one can identify 1-2 novel classes of compounds to further improve potency and drug-like properties.
Additional ADME/Tox: This is a list of additional information on absorption, distribution, metabolism, excretion (ADME) and toxicity on the compounds. The more favorable information the compounds have, the more the compounds are as drug candidates and higher likelihood of attracting a commercial partner.
Column A lists the information requested in each section of the guide (Column E gives a detailed description of the information being requested).
Column B called “status of experiment” is to be color coded if the requested information on the row is being obtained. If the experiment is completed and the results are positive the box will be colored green. If the experiment is completed and the results are negative then it is colored red. If the results are ambiguous, then it is colored yellow. Lastly, if the experiment is ongoing then it is blue. Otherwise the box remains blank.
Column C contains a numerical score that ranks the importance of the information for advancing the technology, with 5 being of highest importance and 1 being lowest. For example, in Section II, the existence of assays with reliable readouts is given a value of 5 because, in the absence of such assays, the program cannot advance.
Column D is for a brief description of the experimental outcome. It is up to the individual updating the template to decide on level of detail. (Please see Examples 1-3).
Column E gives a brief description on the information that is being requested. For information related to ADME/Tox, we have also included a list of CROs and cost estimates for each experiment to help budget a drug discovery program. Please note that these estimates will vary according to the specifics of the experiments and choice of CRO.
Examples
In Example 1, the set of compounds that were studied satisfied many of the criteria for “drug likeness”. However, in this program, there were issues with potency, novelty, and metabolic stability. This program also focused on a known target which means that it is likely that other companies and research groups have been working on a similar program. This program will likely attract little or no commercial interest unless these issues associated with compounds can be overcome.
In Example 2, the majority of the compounds was active in the xenograft model and showed “drug-like” properties from in-silico and experimental data. However, the animal studies showed moderate toxicity but the results were ambiguous. Since this program is for a cancer of no known treatment, the toxicity issues of these compounds may be tolerated. This program will likely attract commercial interest.
In Example 3, there were 2 novel series of compounds and had “drug-like” properties. The only issue is whether the preliminary measure of bioavailability is sufficient for this indication. The profile of this program will likely lead to commercial interest.