1952251-28-3
1952251-28-3 structure
- Name: TAK-659 hydrochloride
- Chemical Name: TAK-659 (hydrochloride)
- CAS Number: 1952251-28-3
- Molecular Formula: C17H22ClFN6O
- Molecular Weight: 380.85
- Catalog: Signaling Pathways Protein Tyrosine Kinase/RTK Syk
- Create Date: 2018-04-18 08:06:30
- Modify Date: 2024-01-02 13:37:15
-
TAK-659 hydrochloride is a potent, selective and orally available spleen tyrosine kinase (Syk) inhibitor with an IC50 of 3.2 nM.
| Name | TAK-659 (hydrochloride) |
|---|---|
| Synonyms | TAK-659 |
| Description | TAK-659 hydrochloride is a potent, selective and orally available spleen tyrosine kinase (Syk) inhibitor with an IC50 of 3.2 nM. |
|---|---|
| Related Catalog | |
| Target |
IC50: 3.2 nM (Syk)[1] |
| In Vitro | In a cell proliferation assay, TAK-659 shows inhibition toward a SYK-dependent cell line (OCILY10). TAK-659 is shown to be sensitive toward FLT3-ITD dependent cell lines, MV4-11 and MOLM-13 while the WT FLT3 RS4-11 (ALL cell line) and RA1 (Burkitt’s Lymphoma cell line) are not sensitive toward TAK-659. The sensitivity to TAK-659 is associated with mutations impacting SYK activity in B cell lymphomas, whereas TAK-659 is not cytotoxic for adherent primary or solid tumor cell lines[1]. TAK-659 inhibits the microenvironment-induced activation of Syk and downstream signaling molecules, without inhibiting the protein homologue ZAP-70 in T cells. Importantly, the pro-survival, proliferative, chemoresistant and activation effects promoted by the microenvironment are abrogated by TAK-659, which furthermore blocks CLL cell migration toward BMSC, CXCL12, and CXCL13[2]. |
| In Vivo | TAK-659 is currently undergoing Phase I clinical trials for advanced solid tumor and lymphoma malignancies, a Phase Ib study in advanced solid tumors in combination with nivolumab, and PhIb/II trials for relapsed/refractory AML. TAK-659 blocks anti-IgD (immune-globulin D antibody) stimulated CD86 expression in mouse peripheral B cells in vivo. In the OCI-LY10 xenograft and DLBCL PHTX-95L (primary human tumor graft from DLBCL patient) mouse models, TAK-659 demonstrates potent tumor growth inhibition (TGI) after 20 days of treatment. In the FLT3-dependent MV4-11 xenograft model, TAK-659 shows tumor regression at 60 mg/kg daily after 20 days of dosing[1]. |
| References |
| Molecular Formula | C17H22ClFN6O |
|---|---|
| Molecular Weight | 380.85 |
| Storage condition | Please store the product under the recommended conditions in the Certificate of Analysis. |
| Water Solubility | DMSO: 10 mM (Need Ultrasonic and Warming) |
| Hazard Codes | N |
|---|