ArticleBlood advances2023
Antileukemic properties of the kinase inhibitor OTSSP167 in T-cell acute lymphoblastic leukemia.
Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
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- Allogeneic Hematopoietic Stem Cell Transplantation for Infant Leukemia: A Single-Center Case Series and Narrative Review.Children (Basel, Switzerland) · 2025Review
- The reprogramming factor KLF4 in normal and malignant blood cells.Frontiers in immunology · 2025Review
- Identification of common hub genes and construction of immune regulatory networks in aplastic anemia, myelodysplastic syndromes, and acute myeloid leukemia.Frontiers in immunology · 2025Article
- Maternal Embryonic Leucine Zipper Kinase (MELK) as a Promising Therapeutic Target in Triple Negative Breast Cancer.Anti-cancer agents in medicinal chemistry · 2025Review
- Article
- Pharmacological inhibition of the MAP2K7 kinase in human disease.Frontiers in oncology · 2024Review
- Rational Design of Highly Potent and Selective Covalent MAP2K7 Inhibitors.ACS medicinal chemistry letters · 2023Article
- Implication of Dynamin-2 (DNM2) Mutations in Adult T-cell Acute Lymphoblastic Leukemia.Asian Pacific journal of cancer prevention : APJCP · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Novel drugs are needed to increase treatment response in children with high-risk T-cell acute lymphoblastic leukemia (T-ALL). Following up on our previous report on the activation of the MAP2K7-JNK pathway in pediatric T-ALL, here we demonstrate that OTSSP167, recently shown to inhibit MAP2K7, has antileukemic capacity in T-ALL. OTSSP167 exhibited dose-dependent cytotoxicity against a panel of T-ALL cell lines with IC50 in the nanomolar range (10-50 nM). OTSSP167 induces apoptosis and cell cycle arrest in T-ALL cell lines, associated at least partially with the inhibition of MAP2K7 kinase activity and lower activation of its downstream substrate, JNK. Other leukemic T-cell survival pathways, such as mTOR and NOTCH1 were also inhibited. Daily intraperitoneal administration of 10 mg/kg OTSSP167 was well tolerated, with mice showing no hematological toxicity, and effective at reducing the expansion of human T-ALL cells in a cell-based xenograft model. The same dosage of OTSSP167 efficiently controlled the leukemia burden in the blood, bone marrow, and spleen of 3 patient-derived xenografts, which resulted in prolonged survival. OTSSP167 exhibited synergistic interactions when combined with dexamethasone, L-asparaginase, vincristine, and etoposide. Our findings reveal novel antileukemic properties of OTSSP167 in T-ALL and support the use of OTSSP167 as an adjuvant drug to increase treatment response and reduce relapses in pediatric T-ALL.
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