Assaying Compound Activity

Depending on the project, assaying compound activity typically involves acquiring the compound and then getting it tested either in house or sending it out somewhere to be tested. This page details some of the common tasks and considerations in this process. Note, this information is somewhat specific to the Shoichet lab at UCSF.

Buying Compounds

Identifying Compounds to Buy

Depending on the project, compounds may have different requirements

• In vitro testing
  • Purity: If possible get the compounds at 95% or greater purity even if it costs 100$ or 200$ more. If it's tested to be active but has low purity, it will likely need to be re-purified and then tested.
  • Aggregation: Check the compound with the aggregator advisor (advisor.bkslab.org) and if it's close to or known to be an aggregator (indications include uM nonspecific activity, logP great than 3 or actually shown to be an aggregator through appropriate controls) then either skip the compound or plan on doing aggregation controls, e.g. testing for detergent sensitive nonspecific activity, determine particle formation using DLS, or perform the assay with/without detergent (and just detergent controls).
  • Amount: try to get 10mg if possible, but if it's very expensive you can get less. If you're sending it to a CRO sending it in solution usually requires less compound. If you're planning on further controls (e.g. for purity, aggregation), make sure to get enough.

• In vivo testing
  • Check pharmacokinetics (ask an expert)

Finding Vendors

The easiest way to find vendors is through the ZINC portal. Once you login, go to Manage Carts in the upper right and then create new cart, where you put in a list of smiles or zinc ids. Once you've verified these are the right compounds, click purchasability report where it lists which compounds are available from which vendors. In selecting vendors keep the following in mind

• Here are some reliable vendors
  • AK Sientific (in SF)
  • Toronto Research Chemicals
  • Sigma Aldrich (sometimes higher prices but reliable)
  • Enamine (has a large catalog, in europe)
  • ChemBridge (in SF)
  • Santa Cruz Biotech (in CA)
• Some vendors are just resellers, which makes them have larger catalogs, but can increase the price and take longer. Though often this is offset by the ease of use and not having to pay multiple shipping and handling costs.
  • MolPort (ieva.kluga@molport.com has been the contact as of July 2014)
  • EMolecules
  • Ambinter
• If possible try to group multiple compounds per vendor to reduce shipping and handling costs
• Sometimes compounds are available from special catalogs
  • NCI Platted: 1) Here is a description of the NCI Platted process from there end NCI_Platted. Look up the NCS identifier in PubChem. 2) submit a request form through their webpage. Contact the industry contacts officer at ucsf (Esteban.Mendoza@ucsf.edu | t: 415-502-1599) to have him sign the "Simple Letter of Agreement". He'll will give you a materials transfer form that you need to fill out.
• Remember that our lab will continue to buy from these vendors so be nice, and inquire if we can get a lab discount
• For each compound record
  • ZincID, supplier, supplier product code, molecular weight, purity

Ordering Compounds

• Get quotes either through the webpage or through vendor contacts
• Get Brian to approve the orders costing more than 500USD.
• Forward quotes to Yvonne or whoever is doing the ordering
  • • Be cognizant of the hours the orderer works, sometimes they share time with other labs
    • the quote should including the zincid, vendor, vendor id, amount, and price
    • lookup the project grant number (or ask Brian),
    • a shipping address
    • whose project this is for
    • who should receive the compounds
    • indicate if the order should be rushed (unless necessary, rushed orders should be avoided as they are generally much more expensive)

Testing Compounds with CRO

• If the vendor is not in the BearBuy system, they will need to fill out a form that Yvonne can provide
• Get a quote from the company and give it to Yvonne or whoever is doing the ordering
  • Make sure to include a phone number contact
  • indicate if the order should be rushed (unless necessary, rushed orders should be avoided as they are generally much more expensive)
• Testing concentrations
  • If the supply of compound is limited, often less is required if it is sent in solution, but it is easier and more stable to send powder, so check with the assay vendor
  • If it is subtantially cheaper, and nothing else is known see if the CRO can start with a single dose at 30uM and if there is activity then reduce by half log or (1/3) for 5-10 to generate data for dose response curves