Delving into the Latest Updates on Miristen with Synapse

Overview

Basic Info

Drug Type

Oligonucleotide

Synonyms-

Target

miR-126

Action

antagonists

Mechanism

miR-126 antagonists(microRNA 126 antagonists), Epigenetic drug

Therapeutic Areas

NeoplasmsHemic and Lymphatic Diseases

Active Indication

Recurrent Acute LeukemiaRefractory acute myeloid leukemiaAdult Acute Myeloblastic Leukemia+ [1]

Inactive Indication-

Originator Organization

City of Hope National Medical Center

Active Organization

City of Hope National Medical Center

Inactive Organization-

License Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure/Sequence

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This phase I trial tests the safety, side effects, and best dose of miRisten in treating patients with acute myeloid leukemia (AML) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). MiRisten may stop the growth of cancer cells by blocking some of the molecules needed for cell growth. Giving miRisten may be safe, tolerable and/or effective in treating patients with relapsed or refractory AML.

Start Date24 Oct 2025

Sponsor / Collaborator

City of Hope National Medical Center

[+1]

100 Clinical Results associated with Miristen

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100 Translational Medicine associated with Miristen

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100 Patents (Medical) associated with Miristen

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3

Literatures (Medical) associated with Miristen

05 Mar 2026·BLOOD

Pharmacological inhibition of miR-126 enhances venetoclax activity in acute myeloid leukemia

Article

Author: Buettner, Ralf ; Li, Zhuo ; Valerio, Melissa ; Fu, Yu-Hsuan ; He, Xin ; Li, Ling ; Marcucci, Guido ; Guo, Wancheng ; Kuo, Ya-Huei ; Blackmon, Amanda ; Zhang, Lianjun ; Lu, Xiyuan ; Pirrotte, Patrick ; Chen, Zhenhua ; Garcia-Mansfield, Krystine ; Ghoda, Lucy ; Chen, Ying-Chieh ; Nguyen, Le Xuan Truong ; Pathak, Khyatiben ; Kang, HyunJun ; Zhang, Bin ; Hoang, Dinh Hoa

Abstract:

Leukemic stem cells (LSCs) in acute myeloid leukemia (AML) depend on oxidative phosphorylation (OXPHOS) sustained by fatty acid oxidation (FAO) and mitochondrial fusion (mitofusion). In this study, we demonstrate that microRNA-126 (miR-126) maintains LSC function by promoting B-cell lymphoma 2 (BCL-2)–dependent FAO, OXPHOS, and mitofusion, whereas its inhibition disrupts mitochondrial metabolism, induces mitochondrial fission (mitofission), and triggers apoptosis. Mechanistically, miR-126 stabilizes BCL-2 through the SPRED1/extracellular signal-regulated kinase axis, which upregulates CPT1B (FAO) and NRF2 (antioxidant response) while regulating mitochondrial dynamics through DRP1 phosphorylation (inhibiting mitofission) and MFN1/2 phosphorylation (enhancing mitofusion). miRisten, a CpG-conjugated anti–miR-126 oligonucleotide now in clinical trials (NCT07025564), synergized with venetoclax (VEN) to suppress FAO/OXPHOS, promote mitofission, and impair LSC homeostasis. In vivo, miRisten potentiated the VEN/azacitidine regimen, an US Food and Drug Administration-approved therapy for older or unfit patients with AML, significantly prolonging survival in patient-derived xenograft models. VEN/miRisten combination also reduced LSC burden and restored VEN sensitivity, establishing miR-126 inhibition as a transformative therapeutic strategy for AML.

01 Oct 2021·Clinical and translational medicineQ2 · MEDICINE

Targeting miR‐126 disrupts maintenance of myelodysplastic syndrome stem and progenitor cells

Q2 · MEDICINE

ArticleOA

Author: Yiyi Yao ; Bin Zhang ; Jie Jin ; Guido Marcucci ; Herman Wu ; Monzr M. Al Malki ; Jie Sun ; Ling Li ; Anthony S. Stein ; Huafeng Wang ; Nadia Carlesso ; Ya-Huei Kuo ; Tinisha McDonald ; Flavia Pichiorri ; Dandan Zhao ; Dan Dong ; Yingwan Luo ; Xia Li ; Hongyan Tong

Abstract:

Background:

Myelodysplastic syndrome (MDS) arises from a rare population of aberrant hematopoietic stem and progenitor cells (HSPCs). These cells are relatively quiescent and therefore treatment resistant. Understanding mechanisms underlying their maintenance is critical for effective MDS treatment.

Methods:

We evaluated microRNA‐126 (miR‐126) levels in MDS patients’ sample and in a NUP98‐HOXD13 (NHD13) murine MDS model along with their normal controls and defined its role in MDS HSPCs’ maintenance by inhibiting miR‐126 expression in vitro and in vivo. Identification of miR‐126 effectors was conducted using biotinylated miR‐126 pulldown coupled with transcriptome analysis. We also tested the therapeutic activity of our anti‐miR‐126 oligodeoxynucleotide (miRisten) in human MDS xenografts and murine MDS models.

Results:

miR‐126 levels were higher in bone marrow mononuclear cells from MDS patients and NHD13 mice relative to their respective normal controls (P < 0.001). Genetic deletion of miR‐126 in NHD13 mice decreased quiescence and self‐renewal capacity of MDS HSPCs, and alleviated MDS symptoms of NHD13 mice. Ex vivo exposure to miRisten increased cell cycling, reduced colony‐forming capacity, and enhanced apoptosis in human MDS HSPCs, but spared normal human HSPCs. In vivo miRisten administration partially reversed pancytopenia in NHD13 mice and blocked the leukemic transformation (combination group vs DAC group, P < 0.0001). Mechanistically, we identified the non‐coding RNA PTTG3P as a novel miR‐126 target. Lower PTTG3P levels were associated with a shorter overall survival in MDS patients.

Conclusions:

MiR‐126 plays crucial roles in MDS HSPC maintenance. Therapeutic targeting of miR‐126 is a potentially novel approach in MDS.

Nature communicationsQ1 · CROSS-FIELD

Targeting miR-126 in inv(16) acute myeloid leukemia inhibits leukemia development and leukemia stem cell maintenance

Q1 · CROSS-FIELD

ArticleOA

Author: Swiderski, Piotr ; Brewer, Casey J ; Nguyen, Le Xuan Truong ; Chen, Ying-Chieh ; He, Xin ; Cook, Guerry J ; Kortylewski, Marcin ; Wu, Dijiong ; Kuo, Ya-Huei ; Li, Shu ; Hua, Wei-Kai ; Zhang, Bin ; Zhao, Dandan ; Cai, Qi ; Hoang, Dinh Hoa ; Wu, Xiwei ; Li, Ling ; Carnahan, Emily ; Marcucci, Guido ; Chen, Wei ; Rockne, Russell C ; Li, Man ; Qi, Jing ; Zhang, Lianjun ; Dong, Haojie

Abstract:

Acute myeloid leukemia (AML) harboring inv(16)(p13q22) expresses high levels of miR-126. Here we show that theCBFB-MYH11 (CM)fusion gene upregulates miR-126 expression through aberrant miR-126 transcription and perturbed miR-126 biogenesis via the HDAC8/RAN-XPO5-RCC1 axis. Aberrant miR-126 upregulation promotes survival of leukemia-initiating progenitors and is critical for initiating and maintaining CM-driven AML. We show that miR-126 enhances MYC activity through the SPRED1/PLK2-ERK-MYC axis. Notably, genetic deletion of miR-126 significantly reduces AML rate and extends survival in CM knock-in mice. Therapeutic depletion of miR-126 with an anti-miR-126 (miRisten) inhibits AML cell survival, reduces leukemia burden and leukemia stem cell (LSC) activity in inv(16) AML murine and xenograft models. The combination of miRisten with chemotherapy further enhances the anti-leukemia and anti-LSC activity. Overall, this study provides molecular insights for the mechanism and impact of miR-126 dysregulation in leukemogenesis and highlights the potential of miR-126 depletion as a therapeutic approach for inv(16) AML.

100 Deals associated with Miristen

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Recurrent Acute Leukemia	Phase 1	United States	City of Hope National Medical Center	24 Oct 2025
Refractory acute myeloid leukemia	Phase 1	United States	City of Hope National Medical Center	24 Oct 2025
Adult Acute Myeloblastic Leukemia	Preclinical	United States	City of Hope National Medical Center	12 Dec 2022
Philadelphia chromosome positive chronic myelogenous leukemia	Preclinical	United States	City of Hope National Medical Center	12 Dec 2022