Evidence map›Paper›PMID 34221866›Full record

ArticleActa pharmaceutica Sinica. B2021

Preclinical efficacy against acute myeloid leukaemia of SH1573, a novel mutant IDH2 inhibitor approved for clinical trials in China.

Zhiqiang Wang, Zhibo Zhang, Yong Li, Li Sun, Dezhen Peng, Danyu Du, Xian Zhang, Luwei Han, Liwen Zhao, Ligong Lu and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta pharmaceutica Sinica. B, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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

13 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. State of the Art of IDH Inhibitors: Emerging Questions and Perspectives.Anti-cancer agents in medicinal chemistry · 2026
    Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Active fractions of golden-flowered tea (Frontiers in nutrition · 2022
    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

13 authors.

Zhiqiang WangJiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210003, China.
Zhibo ZhangJiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210003, China.
Yong LiZhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China.
Li SunJiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210003, China.
Dezhen PengJiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210003, China.
Danyu DuJiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210003, China.
Xian ZhangSanhome Pharmaceutical Co., Ltd., Nanjing 210000, China.
Luwei HanSanhome Pharmaceutical Co., Ltd., Nanjing 210000, China.
Liwen ZhaoSanhome Pharmaceutical Co., Ltd., Nanjing 210000, China.
Ligong LuZhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China.
Hongzhi DuSchool of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
Shengtao YuanJiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210003, China.
Meixiao ZhanZhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults, with increasing incidence with age and a generally poor prognosis. Almost 20% of AML patients express mutant isocitrate dehydrogenase 2 (mIDH2), which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate (2-HG), resulting in poor prognosis. Thus, global institutions have been working to develop mIDH2 inhibitors. SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised. We have conducted a comprehensive study on its pharmacodynamics, pharmacokinetics and safety. First, SH1573 exhibited a strong selective inhibition of mIDH2 R140Q protein, which could effectively reduce the production of 2-HG in cell lines, serum and tumors of an animal model. It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models. Then, it was confirmed that SH1573 possessed characteristics of high bioavailability, good metabolic stability and wide tissue distribution. Finally, toxicological data showed that SH1573 had no effects on the respiratory system, cardiovascular system and nervous system, and was genetically safe. This research successfully promoted the approval of SH1573 for clinical trials (CTR20200247). All experiments demonstrated that, as a potential drug against mIDH2 R140Q acute myeloid leukaemia, SH1573 was effective and safe.

Indexed as

2-HG, 2-hydroxyglutaric acid2-HydroxyglutarateAcute myeloid leukaemiaADME, absorption, distribution, metabolism and excretionAG-221, enasidenibAML, acute myeloid leukemiaAUC, area under the cureBCRP, breast cancer resistance proteinCDX, cell-line-derived xenograftCYP, cytochrome P450DifferentiationEPO, erythropoietinIC50, half maximal inhibitory concentrationLC–MS/MS, liquid chromatography–tandem mass spectrometryMDR1, multidrug resistance protein 1mIDH2 inhibitormIDH2, mutant isocitrate dehydrogenaseMutant isocitrate dehydrogenase 2 (mIDH2)OAT, organic anion transporterOATP, organic anion transporting polypeptideOCT, organ cation transporterPapp, apparent permeability coefficientPD, pharamacodynamicsPDX, patient-derived tumor xenograftPK, pharmacokineticsPreclinical efficacySH1573Tumor metabolismα-KG, α-ketoglutaric acid

Identifiers

PMID34221866
PMCPMC8245910

What OpenQuestion holds

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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.