Compound Request Procedures (Vialed Samples and Plated Sets)
Requestors should have the following required information before starting the ordering process:
- Requestor's contact/shipping information
- A 9-digit FedEx number
- NSC number of sample (use "Data Search" at DTP homepage)
- For vialed samples: milligram amount to be requested (10 mg MAX)
- For plated sets: plate type and iteration (1 plate copy per investigator MAX)
- Brief description of the screening process or intended use of materials (e.g., CDK screening assay standard)
- Contact information, including e-mail, of Organization's signatory authority for accepting Simple Letter of Agreement for Materials Transfer (SLA)
Vialed Sample Requests
The DTP makes samples of select agents available in small amounts (based on availability) from our Open Chemical Repository compounds for non-clinical research purposes. Investigators should determine their research requirements, and then request the minimum amount of each compound. Although there is no fee for each sample, researcher recipients are required to cover shipping charges by supplying an account number from FedEx.
Each sample request will be considered based on various factors, including current inventory and the information provided by researchers in the "assay description" field that justifies the quantities being sought. Requesters will need to provide significant experimental details to justify the release of more than the 10-milligram maximum that would exceed a typical in vitro assay. Samples of most FDA-approved oncology drugs are limited to 5-milligram quantities.
Please note that an individual with the appropriate signatory authority from the investigator's organization will be required to accept an online Simple Letter of Agreement (SLA) for material transfer before the compound order is forwarded for DTP approval. The SLA will be sent electronically by DTP to the designated signatory authority at the end of the ordering process. Vialed samples or plated sets are generally shipped within one week after approval by DTP staff.
To recognize NCI's contribution, investigators shall add the following statement to the acknowledgement section of their publication:
"The PI wishes to thank the National Cancer Institute Developmental Therapeutics Program (NCI/DTP) for providing compounds present in this (poster, manuscript, presentation, etc.). Specifically, NSC #: X, Y, Z , etc."
Technical Difficulties
Technical difficulties encountered with the online submission process should be addressed to:
David C. McCutcheon, Ph.D.
Drug Synthesis and Chemistry Branch
Developmental Therapeutics Program
National Cancer Institute
Dave.McCutcheon@nih.gov
Plated Set Requests
Plated compound sets, both diverse and focused, are available to investigators for non-clinical research purposes. There is no charge for the sets except for shipping costs. Current policy limits investigators to one (1) copy of each plated set. Thereafter, investigators are encouraged to request hits for follow up as individual vialed samples.
Plated samples are generally solubilized in DMSO and provided in frozen 96-well microtiter plates. A plate map is included with each shipment of plates which indicates the accession number of the compound in each well. In many cases the individual samples have not been analyzed for the accuracy of the structural information or for the purity of the sample unless otherwise indicated in the set description.
To recognize NCI's contribution, investigators shall add the following statement to the acknowledgement section of their publication:
"The PI wishes to thank the National Cancer Institute Developmental Therapeutics Program (NCI/DTP) for providing compounds present in this (poster, manuscript, presentation, etc.). Specifically, NSC #: X, Y, Z , etc."
Available Plated Compound Sets
Approved Oncology Drugs Set XI Information
FDA-approved oncology drugs for cancer research
This plated set (3 microtiter plates/set) contains the most current FDA-approved anticancer drugs. The current set (AOD XI) consists of 179 agents and is intended to be used in cancer research, drug discovery and combination drug studies. Compounds in this set are provided as 20 microliters at a 10mM concentration in 100% DMSO on Greiner 650201 96-well PP U-bottom plates; plates are shipped frozen, with dry ice. All proprietary agents in this set were obtained through commercial sources. All compounds were found to have satisfactory purity and identity. In general, substances were checked by both NMR and LC-MS. For recently acquired compounds, the supplier's Certificate of Analysis was accepted.
Diversity Set VII Information
The NCI Diversity Set VII of 1581 compounds is available on Greiner 650201 96-well PP U-bottom plates. Compounds are arrayed at 20 uL/10 mM in DMSO.
The NCI Diversity Set VII was derived from the almost 140,000 compounds available for distribution from the DTP repository. Only compounds having at least 250 mg of material available were considered. The final set was selected using the programs Chem-X (Oxford Molecular Group) and Catalyst (Accelrys, Inc.). These programs use defined pharmacophoric centers (i.e., hydrogen bond acceptor, hydrogen bond donor, positive charge, aromatic, hydrophobic, acid, base) and defined distance intervals to create a finite set of three dimensional, 3-point pharmacophores. The set results in over 1,000,000 possible pharmacophores for the Diversity Set VII selection. The selection protocol considers each molecule, all its pharmacophores, and each of its conformational isomers. During the generation of the diversity set, the pharmacophores for any candidate compound were compared to the set of all pharmacophores found in structures already accepted into the set. If the current structure had more than 5 new pharmacophores, it was added to the set. An additional objective was to create a diverse set of compounds that would be amenable to forming structure-based hypotheses. Thus, molecules that were relatively rigid, with 5 or fewer rotatable bonds, tending to be planar, 1 or less chiral centers, and pharmacologically desirable features (i.e., did not contain: obvious leaving groups, weakly bonded heteroatoms, organometallics, polycyclic aromatic hydrocarbons, etc.) were given priority in the final selection. This resulted in a set of 1581 compounds. All compounds were checked for purity via LC/Mass Spec. and found to have a purity of 90% or better by this method.
Mechanistic Set VI information
The Mechanistic Set VI is available on Greiner 650201 96-well PP U-bottom plates. Compounds are arrayed at 20 μL/1 mM in DMSO.
The Mechanistic Set VI, which consists of 802 compounds, was derived from the 37,836 open compounds that have been tested in the NCI human tumor 60 cell line screen. In contrast to the diversity set, which was chosen based on structural diversity, this mechanistic diversity set was chosen to represent a broad range of growth inhibition patterns in the 60-cell line screen, based on the GI50 activity of the compounds. Compounds that have been tested in the 60-cell line screen were clustered using the FASTCLUS procedure in the SAS statistical package. This algorithm is based on MacQueen's k-means algorithm, which minimizes the sum of squared distances from the cluster means. The procedure resulted in 1272 clusters. A single representative compound from each cluster, for which an adequate supply of material was available, was chosen. Some clusters are not represented in the set, as insufficient material was available.
Natural Products Set V Information
The Natural Products Set V consists of 390 compounds that were selected from the DTP Open Repository collection of 140,000 compounds. Factors in selection were origin, purity (>90% by ELSD, major peak has correct mass ion), structural diversity and availability of compound. This set was created in response to numerous drug discovery research groups that expressed a desired to study a variety of scaffold structures having multiple functional groups. The compounds are arrayed across two 384-well polypropylene (PP) microtiter plates. The two outside rows and columns of each plate are left empty. Well E15 of plate 13190761 contains DMSO with no drug. Each well contains 20 uL of 10 mM DMSO solution.
Questions
Questions regarding plated sets or plate contents should be directed to:
Timothy Taylor (taylort4@mail.nih.gov).
Frequently Asked Questions (FAQ)
What is an "Open" Compound?
We refer to "Open" compounds as agents that have structures which are in the public domain. Please note that not all Open compounds are available for distribution from the NCI/DTP Open Chemicals Repository.
How does one acknowledge the NCI's contribution in a manuscript or other publication?
To recognize NCI's contribution, investigators shall add the following statement to the acknowledgement section of their publication:
"The PI wishes to thank the National Cancer Institute Developmental Therapeutics Program (NCI/DTP) for providing compounds present in this (poster, manuscript, presentation, etc.). Specifically, NSC #: X, Y, Z , etc."
I submitted a request for a certain NSC, and irrespective of the amount, I always get a response that the amount I want to order is "not available." What does this mean?
Unfortunately, it means that the compound is no longer available and there are no plans to re-acquire.
I have not received any confirmation that my order was received. Why is that the case?
Once your compound request is completed, the requesting investigator will receive an auto-email from our system with the order/compound request number. If you have not received an auto-confirmation from our system, then it is likely that we did not receive the request. In such instances, you may want to follow up with us.
I placed an order with NCI/DTP for compounds quite some time ago, but I have not received the samples.
It is often the case that the requesting investigators' Signatory Authority has not approved the request internally. Therefore, we are unable to process the request because the Simple Letter of Agreement (SLA) stipulating the terms of the use, etc. of the material has not yet been accepted. Please check with your Technology Transfer Office or legal department to make sure that your order has been approved internally.
I placed an order for gram quantities of a certain NSC but received substantially less material. Why is that the case?
Each submission for material from our repository is regarded as a request. There are no assurances that the requested amount will be supplied, but we do our best to accommodate the requested amounts based on various factors. One of these factors is the information provided by researchers in the "assay description" field that justifies the quantities being sought. In instances where substantial amounts of material are being requested (an amount that would exceed what is typically necessary for in vitro studies), we require significant experimental details to justify the release of considerable quantities of material from the NCI/DTP Open Chemicals Repository. We would like to see specifics regarding the dosing schedule, number of animals being used, background information, etc.
I need to change my Signatory Authority on my order. How do I do this after my order has been placed?
The online order authorization application allows you to change the authorization contact information.
Type the e-mail address of the contact you originally listed:
Click the 'Change Representative' button and input the correct contact information.
What is the purity of the compounds that I am requesting?
The compounds from the NCI/DTP Open Chemicals Repository have been donated from various sources. The chemical structures of these substances are those assigned by the originator of the material. In many cases, the compounds have not been re-analyzed by DTP for accuracy of structure or for the purity of the sample. Due to confidentiality, we are unable to disclose the sources/originators of the supplied agents.
How long will it take for me to receive the compounds?
Compounds are shipped no later than 10-12 business days from the time your active, approved request (by the requesting institution/organization) is received in our queue. However, delays can occur when the compound request is approved internally by your Signatory Authority. There are also instances where some countries require significant paperwork on our end, which could delay your shipment.
Why didn't I receive all the compounds that I ordered?
- Depending on your country's designations of certain agents, some compounds may be classified as "dangerous goods" and we cannot ship those materials.
- We may not have the inventory of the compound.
I placed an order previously under a different SLA. Can I order more material under that SLA?
Yes, however please note that the SLA prohibits the sale of the immediate data or the compounds obtained from the NCI/DTP Open Chemical Repository.
How do I find out status of my order?
Once you have successfully completed the ordering process our system will provide you with a summary of your order with an order/compound request number. If you have not received your compounds within 10 business days and would like to determine the status of your order, please send us a query with the provided order number. This will expedite our response time. If you do not have an order number, but are certain that your order has been placed, please send us the name of the requesting investigator and the date requested.
How do I determine if NCI/DTP has a compound in the Open Chemicals Repository?
Visit the Open Chemicals Repository and search by NSC number or chemical name.
What solvent should I use to dissolve my compounds?
We do not offer advice on the solvents that investigators should utilize in their specific assays. However, many compounds tested in the NCI60 assay are dissolved in DMSO.