JPET peeves: Paper withdrawn after drug company won’t disclose chemical structure

A group of researchers at the drug company ChemoCentryx is withdrawing a 2012 paper in the Journal of Pharmacology and Experimental Therapeutics over failure to appropriately identify the molecule they describe in the article.

The withdrawal notice tells the story:

The following manuscript was published as a Fast Forward article on February 29, 2012:

Sullivan TJ, Dairaghi DJ, Krasinski A, Miao Z, Wang Y, Zhao BN, Baumgart T, Berahovich R, Ertl LS, Pennell A, Seitz L, Miao S, Ungashe S, Wei Z, Johnson D, Boring L, Tsou C-L, Charo IF, Bekker P, Schall TJ, and Jaen JC, Characterization of CCX140-B, an orally bioavailable antagonist of the CCR2 chemokine receptor, for the treatment of type 2 diabetes and associated complications. J Pharmacol Exp Ther jpet.111.190918; doi:10.1124/jpet.111.190918.

It was later found that the chemical identity of a compound cited in the article, CCX140-B, was not sufficiently disclosed. The authors are unable, at this time, to provide the chemical identity of CCX140-B in accordance with the editorial policies of The Journal of Pharmacology and Experimental Therapeutics. As a result, the authors have voluntarily withdrawn this manuscript from publication.

We apologize for any inconvenience this may cause JPET‘s readers.

We spoke with Richard Dodenhoff, journals director for the American Society for Pharmacology and Experimental Therapeutics, which publishes JPET, and he confirmed our suspicions:

We have a policy that chemical structures have to be revealed in a paper. You can’t just use a code name.

In this case, Dodenhoff said, the manuscript “slipped through” the review process and was published as a fast-tracked online article. Recognizing the mistake, the editor contacted the authors, who tried to get permission from the company to disclose the chemical compound but failed.

Without the identity of the compound,

you can’t tell anything from that name what that is; somebody trying to replicate the experiment couldn’t do it.

Which, in the world of drug development, is precisely the point.

We note that GlaxoSmithKline is ChemoCentryx’s development partner:

Our lead independent drug candidate, CCX140, which targets the chemokine receptor CCR2, successfully completed a Phase II clinical trial in type 2 diabetics and is currently in two Phase II clinical trials in patients with diabetic nephropathy, a form of kidney disease. The CCR2 receptor is believed to be of central importance to certain inflammatory diseases, such as diabetic nephropathy and Type 2 diabetes. CCX354, which targets the chemokine receptor CCR1, successfully completed a Phase II proof-of-concept clinical trial for the treatment of rheumatoid arthritis, or RA . This successful Phase II proof-of-concept clinical trial triggered GSK’s option rights under our collaboration agreement. GSK exercised its option to further develop and commercialize CCX354 in November of 2011 and has an exclusive right to initiate a Phase IIb clinical trial for CCX354 in RA. CCR1 plays a significant role in rheumatoid arthritis. CCX168, a complement 5a receptor antagonist, is currently in a Phase II proof-of-concept clinical trial for the treatment of anti-neutrophil cytoplasmic antibody, or ANCA-associated vasculitis, or AAV, and is subject to GSK’s option.

JPET also is retracting an unrelated paper by a group of Chinese researchers who evidently used boluses of the same data in three other publications.

According to the notice:

Re: Ping J, Gao A, Qin H, Wei X, Bai J, Liu L, Li X, Li R, Ao Y, and Wang H (2011) Indole-3-carbinol enhances the resolution of rat liver fibrosis and stimulates hepatic stellate cell apoptosis by blocking the inhibitor of κB kinase α/inhibitor of κB-α/nuclear factor-κB pathway. J Pharmacol Exp Ther 339:694–703; doi:10.1124/jpet.111.179820

The article referenced above contains significant data that have been published in multiple articles in other scientific journals. Portions of the data shown in Figures 1, 2, and 3 and in Table 1 from this paper represent either exact duplication or very close replication of similar experiments reported in at least three other published articles from the authors’ laboratory. The data were republished in JPET without citation to this other work. This is in direct violation of JPET‘s editorial policies and in contradiction to the assurances and statements provided by the authors in the authorship responsibility form that was signed by all of the authors and submitted with their manuscript.

One of those prior publications might be this paper from 2011 in Yao Xue Xue Bao.

Dodenhoff said a reader alerted the journal to the recycled data. The authors, he said,

 felt that it wasn’t duplication but couldn’t really offer any reason why it wasn’t.

Hat tip: Clare Francis