First of all I would like to congratulate you to get a molecule with good docking score. And I would like to add that molecular modelling studies does not guarantee efficient results. It just predicts the results. However there are instances wherein molecules designed using computational studies have come out as potential drug candidates. Therefore, there is a scope for drug discovery using molecular modelling.

The next thing you could do is, synthesize that molecule and evaluate it for its cytotoxicity especially against breast cancer cell lines such as MCF7 or MDA-MB 231 etc. If it is found active then I suggest you to screen it for its effect on estrogen receptor to further confirm its activity against breast cancer.

All the very best. Hope this molecule becomes a potential compound for the treatment of breast cancer.

Mohammed Ali Hussaini Syed..Thnaks for your kind replay...I just tried my molecule with BRCA1 protein only is it necessary to try estrogen receptor?

Hi Byiu

Congrats from my side as well.

First make sure your intellectual property is secured, e.g by contacting your technology transfer person at the university. Then you can (and should, for the potential benefit of patients) share structure and data with groups who are working in the field under the contracts signed, ideally in a pharmaceutical company that knows how to bring molecules to clinic.

They can advise you how to profile the compound further and to hopefully make it a clinical candidate that could go on and help patients.

Wishing you all the best.

Geo

Dear Byju, BRCA1 is normally expressed in breast cells which repair damaged DNA or destroy the cell with damaged DNA. Improper functioning of BRCA1 leads to cancer.

On the other hand, estrogen receptors (ER) are reported to be overexpressed in about 70% of breast cancers. Especially ER alpha is found to be associated with various types of tumors. This is the reason why I have suggested you to screen it for ER otherwise having BRCA1 activity is also worthy. Moreover, tamoxifen is one of the ligands for ER alpha which is a widely used drug to treat breast cancer. You can compare your molecule with tamoxifen, (if possible) experimentally or theoretically by docking it against ER alpha. This could be an added advantage to your molecule.

Thank you for kind replay. I have read some paper they have docked small molecules with BRCA1 protein and the paper itself giving the results that the binding energy was too low. This is why I selected BRCA1 protein. I think I have to dock with estrogen receptor protein for the proof to be anticancer effect on breast cancer. So there is no importance to dock with BRCA1 protein right..?

Dear Byju, Congratulations. Keep up your good work.

BRCA protein is a tumour suppressor protein, the so called "good" protein, which loses its function when mutated. If you are hitting on a protein which can bind to mutated BRCA1, then maybe it will be good to develop it to a diagnostic marker. But first, as suggested earlier, secure your IPR.

Best wishes.

I also suggest you to look at the signaling pathways in breast cancer. Those cells which express ER offer an opportunity to block these estrogen modulated pathways with different blockers like Synthetic Estrogen Receptor Modulator (SERM, eg Tamoxifen) and Aromatase Inhibitors (AI). The efficacy of these agents have been clinically proven over and over again. However, these are the canonical pathways. There are also non-canonical or alternate pathways modulated through intermediaries like mTOR, HER2 etc. Eventually the malignant cells learn to overcome estrogen blockade by resorting to these pathways. In other types which do not express ER, these pathways have significant roles, and all these are potential therapeutic target proteins. Therefore it will be really worthwhile to test your protein against as many targets as you can. Again, secure your IPR.

Its nothing like that, ER is one of the known target for the development of therapeutics for breast cancer. As previously stated tamoxifen is one of the widely used drug that target ER. Similarly BRCA1 is another target which is somehow related to PARP. PARP inhibitors such as BMN 673 (moved to phase 3 clinical trials) are known to inhibit the growth of BRCA1 mutated breast cancers. Both the targets have their own scope for being used for the development of targeted therapies for breast cancer. In my view your compound's activity over BRCA1 would be the evidence for its potential. I hope the attachments would help you to get a clear picture about BRCA1 and PARP.

Thanks Mohammed Ali Hussaini Syed, for the readings. PARP inhibition is today a well appreciated strategy, but what I learnt new is that BRCA 1&2 targets may also hold promise to potentiate PARP inhibitors.

I would still suggest, in order to expand possibilities, that the protein be considered for a diagnostic marker for BRCA. If it should succeed in showing effect against tumour cells, it will be novel and good. But the diagnostics part is still deficient today, - an easy and widely available, affordable diagnostic for BRCA is yet a far cry. If it should stand good there, it would be a welcome breakthrough.

Thank you very much Mohammed Ali Hussaini Syed 

I will continue with the possiblity of synthesis of the molecule and thereby invitro and in vivo studies.