From the journal RSC Chemical Biology Peer review history

14-Jul-2023

Dear Dr Wheelhouse:

Manuscript ID: CB-REV-05-2023-000076
TITLE: Antitumour Imidazotetrazines: Past, Present... and Future?

Thank you for your submission to RSC Chemical Biology, published by the Royal Society of Chemistry. I sent your manuscript to reviewers and I have now received their reports which are copied below.

After careful evaluation of your manuscript and the reviewers’ reports, I will be pleased to accept your manuscript for publication after revisions.

Please revise your manuscript to fully address the reviewers’ comments. When you submit your revised manuscript please include a point by point response to the reviewers’ comments and highlight the changes you have made. Full details of the files you need to submit are listed at the end of this email.

Please submit your revised manuscript as soon as possible using this link :

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You should submit your revised manuscript as soon as possible; please note you will receive a series of automatic reminders. If your revisions will take a significant length of time, please contact me. If I do not hear from you, I may withdraw your manuscript from consideration and you will have to resubmit. Any resubmission will receive a new submission date.

All RSC Chemical Biology articles are published under an open access model, and the appropriate article processing charge (APC) will apply. Details of the APC and discounted rates can be found at https://www.rsc.org/journals-books-databases/about-journals/rsc-chemical-biology/#CB-charges.

RSC Chemical Biology strongly encourages authors of research articles to include an ‘Author contributions’ section in their manuscript, for publication in the final article. This should appear immediately above the ‘Conflict of interest’ and ‘Acknowledgement’ sections. I strongly recommend you use CRediT (the Contributor Roles Taxonomy, https://credit.niso.org/) for standardised contribution descriptions. All authors should have agreed to their individual contributions ahead of submission and these should accurately reflect contributions to the work. Please refer to our general author guidelines https://www.rsc.org/journals-books-databases/author-and-reviewer-hub/authors-information/responsibilities/ for more information.

The Royal Society of Chemistry requires all submitting authors to provide their ORCID iD when they submit a revised manuscript. This is quick and easy to do as part of the revised manuscript submission process. We will publish this information with the article, and you may choose to have your ORCID record updated automatically with details of the publication.

Please also encourage your co-authors to sign up for their own ORCID account and associate it with their account on our manuscript submission system. For further information see: https://www.rsc.org/journals-books-databases/journal-authors-reviewers/processes-policies/#attribution-id

Please note: to support increased transparency, RSC Chemical Biology offers authors the option of transparent peer review. If authors choose this option, the reviewers’ comments, authors’ response and editor’s decision letter for all versions of the manuscript are published alongside the article. Reviewers remain anonymous unless they choose to sign their report. We will ask you to confirm whether you would like to take up this option at the revision stages.

I look forward to receiving your revised manuscript.

Yours sincerely,
Professor Zaneta Nikolovska-Coleska
Associate Editor, RSC Chemical Biology

************

Reviewer 1

Accept with minor amendments. Comments are tracked in the pdf.
Aswell as a clear and succinct review of the discovery of TMZ and future endeavours to discover analogues that will overcome clinical resistance, a very important message is conveyed. Knowledge and consideration of all relevant literature (current and historical), is necessary to avoid potentially catastrophic clinical outcomes.
A very enjoyable and important mini-review.

Reviewer 2

This is a historically interesting account of the discovery of Temozolomide, a drug that is currently the main chemotherapy for the treatment glioma. For the future the propargyl analogue 7 has been synthesised and formulated by the Nottingham team, with potential to overcome side issues linked to Temozolomide, as well as improve delivery to the brain.
The science is well described, and clearly illustrated with well designed Schemes and Figures.

This review should be published subject to the following minor revisions:
I am not sure that this is the forum to criticise major pharma regarding the development of biologics, so please tone down the conclusion, but also mention the potential for compound 7?
Please delete 'What a dismal prospect!'.
Scheme 1 legend....TMZ (2) and MTZ (1).....
Paragraph under scheme 1: Needs editing 'Surviving 'cured' mice died prematurely with shrunken bodies' written twice.
Please check references 21 (delete T. D.), 31 (Hummersone?) and 34 (M. C. J.).

Dear Professor Nikolovska-Coleska

Thankyou for the referees helpful comments to which we are pleased to respond.

Referee 1. The authors thank this referee for their feedback and with the exception of retaining capitalisation of "Chemistry" the proper noun, we are pleased to include all this reviewer's suggestions for improvement.

Referee 2. The authors thank this referee for their feedback and with the exception of one comment we are pleased to include all this reviewer's suggestions for improvement.

We have altered the tone of the penultimate paragraph in response to both referees' feedback but ask that you exercise your editorial judgement to allow retention of the closing exclamation of exasperation.

Yours sincerely

Richard Wheelhouse
Reader in Medicinal Chemistry, University of Bradford

This text has been copied from the Microsoft Word response to reviewers and does not include any figures, images or special characters:

REVIEWER REPORT(S):

Referee: 1

Comments to the Author
Accept with minor amendments. Comments are tracked in the pdf.
All done. We have retained capitalisation of the proper noun "Chemistry" and altered the tone of the penultimate paragraph in response to both referees' feedback.

As well as a clear and succinct review of the discovery of TMZ and future endeavours to discover analogues that will overcome clinical resistance, a very important message is conveyed. Knowledge and consideration of all relevant literature (current and historical), is necessary to avoid potentially catastrophic clinical outcomes.

A very enjoyable and important mini-review.

Referee: 2

Comments to the Author
This is a historically interesting account of the discovery of Temozolomide, a drug that is currently the main chemotherapy for the treatment glioma. For the future the propargyl analogue 7 has been synthesised and formulated by the Nottingham team, with potential to overcome side issues linked to Temozolomide, as well as improve delivery to the brain.
The science is well described, and clearly illustrated with well-designed Schemes and Figures.

This review should be published subject to the following minor revisions:
I am not sure that this is the forum to criticise major pharma regarding the development of biologics, so please tone down the conclusion, but also mention the potential for compound 7?
Penultimate paragraph rephrased and emphasis on compound 7 added.

Please delete 'What a dismal prospect!'.
We ask that you exercise your editorial judgement to allow retention of the closing exclamation of exasperation.

Scheme 1 legend....TMZ (2) and MTZ (1).....
Fixed

Paragraph under scheme 1: Needs editing 'Surviving 'cured' mice died prematurely with shrunken bodies' written twice.
Fixed

Please check references 21 (delete T. D.), 31 (Hummersone?) and 34 (M. C. J.).
Checked and corrected.

18-Aug-2023

Dear Dr Wheelhouse:

Manuscript ID: CB-REV-05-2023-000076.R1
TITLE: Antitumour Imidazotetrazines: Past, Present... and Future?

Thank you for your submission to RSC Chemical Biology, published by the Royal Society of Chemistry. I sent your manuscript to reviewers and I have now received their reports which are copied below.

After careful evaluation of your manuscript and the reviewers’ reports, I will be pleased to accept your manuscript for publication after minor revision outlined by the reviewer. Although, as you have highlighted in the conclusion there are challenges for development new drugs for brain tumors, it is important to be recognized that there is a significant amount of ongoing research towards developing targerted therapy, immunotherapy, drug repurposing and etc. As the reviewer mentioned, it is important to provide patients and readers with a positive message that in the next forty years there will be advances in the treatment landscape of brain tumors.

Please revise your manuscript to address the reviewer’s comment. When you submit your revised manuscript please include a point by point response to the reviewers’ comments and highlight the changes you have made. Full details of the files you need to submit are listed at the end of this email.

Please submit your revised manuscript as soon as possible using this link :

*** PLEASE NOTE: This is a two-step process. After clicking on the link, you will be directed to a webpage to confirm. ***

https://mc.manuscriptcentral.com/rsccb?link_removed

(This link goes straight to your account, without the need to log in to the system. For your account security you should not share this link with others.)

Alternatively, you can login to your account (https://mc.manuscriptcentral.com/rsccb) where you will need your case-sensitive USER ID and password.

You should submit your revised manuscript as soon as possible; please note you will receive a series of automatic reminders. If your revisions will take a significant length of time, please contact me. If I do not hear from you, I may withdraw your manuscript from consideration and you will have to resubmit. Any resubmission will receive a new submission date.

All RSC Chemical Biology articles are published under an open access model, and the appropriate article processing charge (APC) will apply. Details of the APC and discounted rates can be found at https://www.rsc.org/journals-books-databases/about-journals/rsc-chemical-biology/#CB-charges.

RSC Chemical Biology strongly encourages authors of research articles to include an ‘Author contributions’ section in their manuscript, for publication in the final article. This should appear immediately above the ‘Conflict of interest’ and ‘Acknowledgement’ sections. I strongly recommend you use CRediT (the Contributor Roles Taxonomy, https://credit.niso.org/) for standardised contribution descriptions. All authors should have agreed to their individual contributions ahead of submission and these should accurately reflect contributions to the work. Please refer to our general author guidelines https://www.rsc.org/journals-books-databases/author-and-reviewer-hub/authors-information/responsibilities/ for more information.

The Royal Society of Chemistry requires all submitting authors to provide their ORCID iD when they submit a revised manuscript. This is quick and easy to do as part of the revised manuscript submission process. We will publish this information with the article, and you may choose to have your ORCID record updated automatically with details of the publication.

Please also encourage your co-authors to sign up for their own ORCID account and associate it with their account on our manuscript submission system. For further information see: https://www.rsc.org/journals-books-databases/journal-authors-reviewers/processes-policies/#attribution-id

Please note: to support increased transparency, RSC Chemical Biology offers authors the option of transparent peer review. If authors choose this option, the reviewers’ comments, authors’ response and editor’s decision letter for all versions of the manuscript are published alongside the article. Reviewers remain anonymous unless they choose to sign their report. We will ask you to confirm whether you would like to take up this option at the revision stages.

I look forward to receiving your revised manuscript.

Yours sincerely,
Professor Zaneta Nikolovska-Coleska
Associate Editor, RSC Chemical Biology

************

Reviewer 2

All requested edits addressed, except one. It is the editor's decision, but I would request the deletion of 'What a dismal prospect!' as I don't think it is necessary. Forty years is along time and I predict that biologics and their drug delivery will be developed. Patients and their carers may read this review.....they should be provided with a little hope/optimism!

OK. You are the editor.

This text has been copied from the PDF response to reviewers and does not include any figures, images or special characters:

Dear Professor Nikolovska-Coleska

The contentious final statement has been removed.

Thankyou for your consideration.

Yours sincerely,

18-Aug-2023

Dear Dr Wheelhouse:

Manuscript ID: CB-REV-05-2023-000076.R2
TITLE: Antitumour Imidazotetrazines: Past, Present... and Future?

Thank you for submitting your revised manuscript to RSC Chemical Biology. I am pleased to accept your manuscript for publication in its current form. I have copied any final comments from the reviewer(s) below.

You will shortly receive a separate email from us requesting you to submit a licence to publish for your article, so that we can proceed with the preparation and publication of your manuscript.

All RSC Chemical Biology articles are published under an open access model, and the appropriate article processing charge (APC) will apply. Details of the APC and discounted rates can be found at https://www.rsc.org/journals-books-databases/about-journals/rsc-chemical-biology/#CB-charges.

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Professor Zaneta Nikolovska-Coleska
Associate Editor, RSC Chemical Biology