Evidence map›Paper›PMID 28229434›Full record

ReviewEuropean journal of drug metabolism and pharmacokinetics2017

Preclinical Pharmacokinetics and Pharmacodynamics of Pinometostat (EPZ-5676), a First-in-Class, Small Molecule S-Adenosyl Methionine Competitive Inhibitor of DOT1L.

Nigel J Waters

Abstract readReview
PubMed Publisher
In one paragraph

Review in European journal of drug metabolism and pharmacokinetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

1 author at 1 institution in 1 country.

Nigel J WatersSyros Pharmaceuticals, 620 Memorial Drive, Cambridge, MA, 02139, USA. nwaters@syros.com.
Swim Across America · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acute leukemias bearing mixed lineage leukemia (MLL) rearrangements are aggressive diseases characterized by a poor overall prognosis despite multi-agent chemotherapy. Aberrant fusion proteins involving the MLL histone methyltransferase (HMT) lead to recruitment of DOT1L, to a multi-protein complex resulting in aberrant methylation of histone H3 lysine 79 at MLL target genes, and ultimately enhanced expression of critical genes for hematopoietic differentiation, including HOXA9 and MEIS1, and as such defines the established mechanism for leukemogenesis in MLL-rearrangement (MLL-r) leukemias. Pinometostat is a first-in-class, small molecule inhibitor of DOT1L with sub-nanomolar affinity and >37,000 fold selectivity against non-MLL HMTs, and was the first member of the novel HMT inhibitor class to enter Phase 1 clinical trials in both adult and pediatric MLL-r leukemia patients. In this article, the preclinical pharmacokinetics/pharmacodynamics and drug disposition of pinometostat are reviewed including discussion of how these data were used to inform early clinical studies, and how they translated to the clinical experience.

Indexed as

AnimalsAntineoplastic AgentsBenzimidazolesHistone-Lysine N-MethyltransferaseHistone MethyltransferasesHumansAntineoplastic AgentsBenzimidazolesEPZ-5676Histone-Lysine N-MethyltransferaseHistone Methyltransferases

Identifiers

PMID28229434
OpenAlexW2590885695

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.