Birelentinib

CAS 2662512-15-2

MF C23H21F2N5O3 MW453.4 g/mol

[(2S,5S)-5-[4-amino-5-[4-(2,3-difluorophenoxy)phenyl]imidazo[5,1-f][1,2,4]triazin-7-yl]oxan-2-yl]methanol

[(2S,5S)-5-{4-amino-5-[4-(2,3-difluorophenoxy)phenyl]imidazo[5,1-f][1,2,4]triazin-7-yl}oxan-2-yl]methanol
tyrosine kinase inhibitor, antineoplastic, DZD8586, DZD 8586, Fast Track designation, BTK-IN-30, Z2F599L9GD

Birelentinib (also known as DZD8586) is a first-in-class, non-covalent dual inhibitor of LYN (lymphocyte-specific protein tyrosine kinase) and BTK (Bruton’s tyrosine kinase).

It is currently being developed by Dizal Pharmaceutical as an oral therapy for various B-cell malignancies. 

Clinical Status and FDA Designations

As of late 2025, birelentinib has received significant attention for its potential in treating resistant blood cancers: 

• Fast Track Designation: In August 2025, the U.S. FDA granted Fast Track designation to birelentinib for adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
• Target Population: It is specifically intended for those who have failed at least two prior therapies, including a covalent BTK inhibitor and a BCL-2 inhibitor.
• Key Trials: It is being evaluated in multiple studies, including the Phase 3 Tai-Shan6 trial comparing it against standard treatments like bendamustine and rituximab. 

Unique Therapeutic Properties

Birelentinib is designed to overcome common drug resistance mechanisms found in existing treatments: 

• Overcoming Resistance: It targets both BTK-dependent pathways (including the common C481X mutation) and BTK-independent B-cell receptor (BCR) signaling pathways.
• Blood-Brain Barrier (BBB) Penetration: A notable feature is its ability to fully penetrate the blood-brain barrier, which may offer therapeutic benefits for patients with central nervous system (CNS) involvement.
• Efficacy: Early Phase 1/2 data presented at the ASH Annual Meeting and EHA Congress in 2025 showed an Objective Response Rate (ORR) of 84.2% in heavily pretreated patients

Birelentinib is an orally bioavailable non-covalent dual inhibitor of tyrosine-protein kinases Lyn (LYN) and BTK (Bruton’s tyrosine kinase; Bruton agammaglobulinemia tyrosine kinase), with potential antineoplastic activity. Upon oral administration, birelentinib targets and inhibits both LYN and BTK, thereby blocking both BTK-dependent and BTK-independent B-cell antigen receptor (BCR) signaling pathways. This prevents the proliferation of malignant B-cells in which the BCR signaling pathway is overactivated. Birelentinib is able to cross the blood-brain barrier (BBB) and thus potentially useful in the treatment of central nervous system (CNS) metastases

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WO2021136219A1

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References

Btk inhibitors

Publication Number: WO-2021136219-A1

Priority Date: 2020-01-02

/////////birelentinib, tyrosine kinase inhibitor, antineoplastic, DZD8586, DZD 8586, Fast Track designation, BTK-IN-30, Z2F599L9GD