The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Discovery of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1 H-benzimidazole-4-carboxamide (ABT-888) for the Treatment of Cancer
Open accessAbstract
We have developed a series of cyclic amine-containing benzimidazole carboxamide PARP inhibitors with a methyl-substituted quaternary center at the point of attachment to the benzimidazole ring system. These compounds exhibit excellent PARP enzyme potency as well as single-digit nanomolar cellular potency. These efforts led to the identification of 3a (2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide, ABT-888), currently in human phase I clinical trials. Compound 3a displayed excellent potency against both the PARP-1 and PARP-2 enzymes with a K(i) of 5 nM and in a C41 whole cell assay with an EC(50) of 2 nM. In addition, 3a is aqueous soluble, orally bioavailable across multiple species, and demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide (TMZ) and in an MX-1 breast cancer xenograft model in combination with either carboplatin or cyclophosphamide.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Calabrese, C. R., Almassy, R., Barton, S., Batey, M. A., Calvert, A. H., Canan-Koch, S., Durkacz, B. W., Hostomsky, Z., Kumpf, R. A., Kyle, S., et al. (2004) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djh005 · Cited by 487
Cited by
PARP inhibition: PARP1 and beyond
Rouleau, M., Patel, A., Hendzel, M. J., Kaufmann, S. H., & Poirier, G. G. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2812 · Cited by 1,298
Mouchiroud, L., Houtkooper, R. H., Moullan, N., Katsyuba, E., Ryu, D., Cantó, C., Mottis, A., Jo, Y.-S., Viswanathan, M., Schoonjans, K., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.016 · Cited by 1,210
Therapeutic applications of PARP inhibitors: Anticancer therapy and beyond
Curtin, N. J., & Szabo, C. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2013.01.006 · Cited by 369
Jones, P., Altamura, S., Boueres, J., Ferrigno, F., Fonsi, M., Giomini, C., Lamartina, S., Monteagudo, E., Ontoria, J. M., Orsale, M. V., et al. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm901188v · Cited by 316
Role for DNA Damage Signaling in Pulmonary Arterial Hypertension
Meloche, J., Pflieger, A., Vaillancourt, M., Paulin, R., Potus, F., Zervopoulos, S., Graydon, C., Courboulin, A., Breuils-Bonnet, S., Tremblay, È., et al. (2014) · Circulation · doi:10.1161/circulationaha.113.006167 · Cited by 254
Metadata
- Authors
- Penning, T. D., Zhu, G.-D., Gandhi, V. B., Gong, J., Liu, X., Shi, Y., Klinghofer, V., Johnson, E. F., Donawho, C. K., Frost, D. J., Bontcheva-Diaz, V., Bouska, J. J., Osterling, D. J., Olson, A. M., Marsh, K. C., Luo, Y., & Giranda, V. L.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2008-12-22
- Volume
- 52
- Issue
- 2
- Pages
- 514-523
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2072471623
- Cited by
- 268
- References
- 1
- FWCI
- 7.70
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Discovery of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1 H-benzimidazole-4-carboxamide (ABT-888) for the Treatment of Cancer. https://app.cochat.ai/papers/10.1021/jm801171j
- The paper
- Penning, T. D., Zhu, G.-D., Gandhi, V. B., Gong, J., Liu, X., Shi, Y., Klinghofer, V., Johnson, E. F., Donawho, C. K., Frost, D. J., Bontcheva-Diaz, V., Bouska, J. J., Osterling, D. J., Olson, A. M., Marsh, K. C., Luo, Y., & Giranda, V. L. (2009). Discovery of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1 H-benzimidazole-4-carboxamide (ABT-888) for the Treatment of Cancer. Journal of Medicinal Chemistry. https://doi.org/10.1021/jm801171j
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
