Evidence map›Paper›PMID 36595522›Full record

ArticlePloS one2023

Novel dual LSD1/HDAC6 inhibitor for the treatment of cancer.

Chandru Gajendran, Subramanyam Janardhan Tantry, Naveen Sadhu M, Zainuddin Mohammed, Purushottam Dewang, Mahanandeesha Hallur, Sreekala Nair, Krishnakumar Vaithilingam, Basavaprabhu Nagayya, Sridharan Rajagopal and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

7 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Epigenetic meets metabolism: novel vulnerabilities to fight cancer.Cell communication and signaling : CCS · 2023
    Review
  7. 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

11 authors at 1 institution in 1 country.

Chandru GajendranJubilant Therapeutics India Ltd, Bangalore, India.
Subramanyam Janardhan TantryDepartment of Medicinal Chemistry, Jubilant Biosys Ltd, Bangalore, India.
Naveen Sadhu MJubilant Therapeutics India Ltd, Bangalore, India.
Zainuddin MohammedJubilant Therapeutics India Ltd, Bangalore, India.
Purushottam DewangDepartment of Medicinal Chemistry, Jubilant Biosys Ltd, Bangalore, India.
Mahanandeesha HallurDepartment of Medicinal Chemistry, Jubilant Biosys Ltd, Bangalore, India.
Sreekala NairDepartment of Discovery Biology, Jubilant Biosys Ltd, Bangalore, India.
Krishnakumar VaithilingamDepartment of Structural Biology, Jubilant Biosys Ltd, Bangalore, India.
Basavaprabhu NagayyaDepartment of Discovery Biology, Jubilant Biosys Ltd, Bangalore, India.
Sridharan RajagopalJubilant Therapeutics India Ltd, Bangalore, India.
Dhanalakshmi SivanandhanJubilant Therapeutics India Ltd, Bangalore, India.ORCID 0000-0002-8095-3869
Jubilant Life Sciences (India) · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dually targeting the epigenetic proteins lysine specific demethylase 1 (LSD1) and histone deacetylases (HDACs) that play a key role in cancer cells by modulating gene repressor complexes including CoREST will have a profound effect in inhibiting tumour growth. Here, we evaluated JBI-097 a dual LSD1/HDAC6 inhibitor, for its in vitro and in vivo activities in various tumor models. In vitro, JBI-097 showed a strong potency in inhibiting LSD1 and HDAC6 enzymatic activities with the isoform selectivity over other HDACs. Cell-based experiments demonstrated a superior anti-proliferative profile against haematological and solid tumor cell lines. JBI-097 also showed strong modulation of HDAC6 and LSD1 specific biomarkers, alpha-tubulin, CD86, CD11b, and GFi1b. In vivo, JBI-097 showed a stronger effect in erythroleukemia, multiple myeloma xenograft models, and in CT-26 syngeneic model. JBI-097 also showed efficacy as monotherapy and additive or synergistic efficacy in combination with the standard of care or with immune checkpoint inhibitors. These and other findings suggest that JBI-097 could be a promising molecule for targeting the LSD1 and HDAC6. Further studies are warranted to elucidate the mechanism of action.

Indexed as

Histone DeacetylasesNeoplasmsCell Line, TumorHistone Deacetylase 6Histone DemethylasesHumansHDAC6 protein, humanHistone Deacetylase 6Histone DeacetylasesHistone Demethylases

Identifiers

PMID36595522
PMCPMC9810167
OpenAlexW4313460610

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Registered trials

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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.