Dear Sir,

You can read the author guidelines and aim of the journal to check whether your manuscript is fit or not for the journal. it you find it is okay and fit you can ask with the publisher with proper reference. Good Luck!

This doesn't sound like unfair treatment; this sounds fairly typical. Unfortuantely, sometimes papers get rejected. There is rarely any point turning it into a fight; it's almost always better to just move on, incorporate the reviewers' suggestions into the paper, and submit to a new journal. The only time I've seen authors successfully contest a decision is when there was clear misconduct, and I don't see any misconduct here, it sounds like just an honest disagreement between reviewers.

Thanks for the reply - we had a look at the scope and we fall within several categories. However, we conducted a screen to establish SAR (Kinase inhibitor screen with >500 known inhibitors) and were able to rationally design 1 compound with activity in vitro and in vivo. We used Novel methodology (our construct is a simplified kinase domain), computational design strategy, high content microscopy, made first ever xtal of the target - this check many boxes, but the one reviewer said we didn't make enough compound to warrant publication. It is clear from the scope that making a large amount of ligands is not necessary; that many areas of med chem would be a fit for this paper. From the list below our paper falls under: 1, 4, 5, 6, and 9.

Journal Scope

The Journal of Medicinal Chemistry publishes studies that contribute to an understanding of the relationship between molecular structure and biological activity or mode of action.

Some specific areas that are appropriate include the following:

1 Design, synthesis, and biological evaluation of novel biologically active compounds, diagnostic agents, or labeled ligands employed as pharmacological tools.

2 Molecular modifications of reported series that lead to a significantly improved understanding of their structure-activity relationships (SAR).

3 Routine extensions of existing series that do not utilize novel chemical or biological approaches or do not add significantly to a basic understanding of the SAR of the series will normally not be accepted for publication.

4 Structural biological studies (X-ray, NMR, etc.) of relevant ligands and targets with the aim of investigating molecular recognition processes in the action of biologically active compounds.

5 Molecular biological studies (e.g., site-directed mutagenesis) of macromolecular targets that lead to an improved understanding of molecular recognition.

6 Computational studies that provide fresh insight into the SAR of compound series that are of current general interest or analysis of other available data that subsequently advance medicinal chemistry knowledge.

7 Substantially novel computational chemistry methods with demonstrated value for the identification, optimization, or target interaction analysis of bioactive molecules.

8 Effect of molecular structure on the distribution, pharmacokinetics, and metabolic transformation of biologically active compounds. This may include design, synthesis, and evaluation of novel types of prodrugs.

9 Novel methodology with broad application to medicinal chemistry, but only if the methods have been tested on relevant molecules.

 My main concern was that out of an initial 4 reviewers, only 1 review is what ultimately influenced the editor to reject our paper. I mean, out of 4 experts, if 3 agree, the paper normally would be accepted - right?

It's not really a vote; maybe from the editor's point of view the one reviewer's points were serious enough to warrant the extra opinion (and ultimately the rejection).

True in the end of the day its up to the editor to weigh in on the reviewers' comments, but the responses of the initial three reviewers were as optimistic as reviewer 2's comments were negative. Also, the reviewer clearly didn't like that we were calling the compound a first generation inhibitor. I've read many papers that publish tool compounds, which find utility in many biological systems, i.e. roscovitine, but clearly are not useful for the clinic.  It seems there is this tacit understanding that to publish in JMedChem large libraries of synthetic ligands are required. In our case, we bypassed this by collecting two kinase inhibitor enriched libraries (only caveat: these were not novel ligands). In my opinion, this was clever as it allowed me to establish SAR without the expenditure of making up to 20 ligands or more; saving precious time and money. All of the other reviewers agreed and made this point; yet it seems that this point constitutes the main ground for dismissal of our paper. Also, there perhaps could be misconduct if the reviewer did not disclose a conflict of interest or knows of another colleague who he might benefit by blocking our paper. I mean, the comments were quite hostile and so contradictory to the other reviewers' comments.

Yes, not disclosing a COI is misconduct, but if I assumed that every reviewer who gave me a negative review was someone with a COI then there would have to be a whole lot of COI in the world.

True, and the review and reviewer may be wholeheartedly honest and sincere, but to discount the other expert reviewers to me seems like poor judgement on the part of the editor. What makes the one reviewer better than the other 3 experts who were extremely positive about the manuscript? Also, we were never given the opportunity to respond to the 5th reviewer, who made a number of points that we addressed in our initial rebuttal letter. In fact, we are not to certain if the 5th reviewer saw our rebuttal. I usually take criticism on the chin, but this process is just abnormal. In my field, manuscripts are normally assigned 3 reviewers. I should point out that my previous lab at UCSF published in this journal on numerous occasions and never have they experienced this type of review process. Also, JMedChem is only an impact 5.5 journal. The calibre of our work is well within remit for this type of journal. In fact (all things must happen for a reason) we've recently re-submitted and our paper is now being considered by an even higher impact journal.

As a final follow up to my question and in a way to partly justify my concern I would like to announce that my paper was just accepted by Oncotarget - a very prestigious cancer journal with a higher impact factor than the original journal. We have corresponded with the editor since his decision and it just came down to the scope of the paper. Our paper is more suited for Oncotarget and the JMedChem editor wasn't comfortable publishing our work without having more SAR data around the new scaffold I identified. I can understand this, but drug discovery in general is within remit for JMedChem; in my opinion he made a poor decision, but he was swayed by one over the top, hostile reviewer. We do suspect a COI, but this will be a mystery for now.