TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK
One of our stated goals was to investigate why retinoic acid receptor (RAR) alpha-selective antagonists showed good binding and activity profiles in vitro but were ineffective in inhibiting spermatogenesis. Samples of GPHR-00193316 (our synthesized sample
| AWARD OVERVIEW |
| Award Number |
3U01HD060479-02S1 |
Funding Agency |
Department of Health and Human Services |
| Total Award Amount |
$98,192 |
Project Location - City |
New York |
| Award Date |
07/19/2010 |
Project Location - State |
NY |
| Project Status |
Completed |
Project Location - Zip |
10032-3702
|
| Jobs Reported |
0.00 |
Congressional District |
15 |
| Project Location - Country |
US |
|
|
Recipient Information
(Grants)
| Recipient Information (Grants) |
|
Recipient Name
|
TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK |
| Recipient DUNS Number |
621889815
|
| Recipient Address |
630 W 168TH ST FL 4 |
| Recipient City |
NEW YORK |
| Recipient State |
New York |
| Recipient Zip |
10032-3725 |
| Recipient Congressional District |
15 |
| Recipient Country |
USA |
Required to Report Top 5
Highly Compensated Officials |
No |
Projects and Jobs Information
| Projects and Jobs Information |
| Project Title |
Admininstrative Supplement to "Retinoid Receptor Antagonists as Novel Male Contraceptives" |
| Project Status |
Completed |
| Final Project Report Submitted |
Yes |
| Project Activities Description |
Medical Research, General/Other |
| Quarterly Activities/Project Description |
We have continued to focus on validating the RARalpha, beta, and gamma cell lines for assessing specificity of the newly developed antagonists. As expected, there was no observable agonistic activity of the known retinoid antagonists. However, there has been a complication and the validation of the antagonist assay is thus still underway due to unexpected behavior of the RARbeta cell line. That is, compounds that should be or should not be antagonistic behave oppositely to the anticipated results. Initially we thought that this may be due to an error either in the plasmid preparation prior to or during transfection. We therefore grew up a new RARbeta TRE cGPS HEK-293 clone to assess whether this clone performs as expected, but the same unexpected behavior was observed. In addition, we determined whether any observed drops in luminescence were the result of antagonistic activity or cell death, using the alamarBlue® cellular toxicity assay and known retinoids. We concluded that the activity assays, with a window up to ~31 nM, can be accepted as antagonistic activity and not an artifact of toxicity. After numerous experiments, we discovered that the unexpected activities of known compounds may be due to the presence of endogenous retinoid X receptors (RXRs) in the original HEK-293 cells. Finally, we have performed a preliminary screen of our newly synthesized retinoids (10 and 100 nM) in a single assay with 100 nM ATRA for assessing antagonist activity and medium alone for the assessing agonist activity. RAC-I-163, RAC-II-19, and RAC-II-131 are clearly RARα antagonists; however, due to the problem of the endogenous RXRs in the cell lines, we cannot conclude that our compounds are RARα selective. Once we have addressed the problem of the RXRs in our cell lines (most likely by using an RXR silencing antagonist), we will repeat the activity screen of our synthesized retinoids and perform a full dose-response study of the promising compounds. |
| Jobs Created |
0.00 |
| Description of Jobs Created |
No jobs were created/retained with Recovery Act funding in this quarter. |
Purchaser Information
(Grants)
| Purchaser Information |
| Contracting Office ID |
Not Reported |
| Contracting Office Name |
Not Available |
| Contracting Office Region |
Not Available |
| TAS Major Program |
75-0840 |
| Award Information |
| Award Date |
07/19/2010 |
| Award Number |
3U01HD060479-02S1 |
| Order Number |
|
| Award Type |
Grants |
| Funding Agency ID |
75 |
| Funding Agency Name |
Department of Health and Human Services |
| Funding Office Name |
Not Available |
| Awarding Agency ID |
75 |
| Awarding Agency Name |
Department of Health and Human Services |
| Amount of Award |
$98,192 |
| Funds Invoiced/Received |
$98,192 |
| Expenditure Amount |
$98,192 |
| Infrastructure Expenditure Amount |
$0 |
| Infrastructure Purpose and Rationale |
Not Reported |
| Infrastructure Point of Contact Name |
Not Reported |
| Infrastructure Point of Contact Email |
Not Reported |
| Infrastructure Point of Contact Phone |
Not Reported |
| Infrastructure Point of Contact Address |
Not Reported |
| Infrastructure Point of Contact City |
Not Reported |
| Infrastructure Point of Contact State |
Not Reported |
| Infrastructure Point of Contact Zip |
Not Reported |
Product or Service Information
(Grants)
| Product or Service Information |
| Primary Activity Code |
H01 |
| Activity Description |
Medical Research, General/Other |
| Sub-Awards Information |
| Sub-awards to Organizations |
0 |
| Sub-award Amounts to Organizations |
$0 |
| Sub-Awards to Individuals |
0 |
| Sub-Award Amounts to Individuals |
$0 |
| Number of Sub-awards less than $25,000/award |
0 |
| Amount of Sub-awards less than $25,000/award |
$0 |
| Number of payments to vendors greater than $25,000 |
0 |
| Total Amount of payments to vendors greater than $25,000/award |
$0 |
| Number of payments to vendors less than $25,000/award |
28 |
| Total Amount of payments to vendors less than $25,000/award |
$6,063 |
| Location Information |
| Latitude, Longitude |
40º 50' 28",
-73º 56' 25" |
| Congressional District |
15 |
| Address 1 |
|
| Address 2 |
|
| City |
New York |
| County |
New York |
| State |
NY |
| Zip |
10032-3702 |
|
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