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| Size | Price | Stock |
|---|---|---|
| 5mg | $98 | 3-6 Days |
| 10mg | $150 | 3-6 Days |
| 25mg | $250 | 3-6 Days |
| 50mg | $430 | 3-6 Days |
| 100mg | $700 | 3-6 Days |
| 250mg | $1250 | 3-6 Days |
| 500mg | $1880 | 3-6 Days |
: Cat #: V3185 CAS #: 1312691-41-0 (2HCl); Purity ≥ 98%
Description: TAK-659 2HCl (TAK659 dihydrochloride) is a novel, potent, highly selective and orally bioavailable spleen tyrosine kinase (Syk) inhibitor with anticancer effects. It inhibits Syk with an IC50 of 3.2 nM. TAK-659 shows inhibition toward a SYK-dependent cell line (OCILY10) in a cell proliferation assay. TAK-659 is shown to be able to inhibit the growth of 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. 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.
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| Molecular Weight (MW) | 417.31 |
|---|---|
| Molecular Formula | C17H21FN6.2HCl |
| CAS No. | 1312691-41-0 (2HCl); |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility In Vitro | DMSO: N/A |
| Water: N/A | |
| Ethanol: N/A | |
| SMILES Code | O=C1NCC2=C1C(C3=CN(C)N=C3)=NC(N[C@H]4[C@@H](N)CCCC4)=C2F.[H]Cl.[H]Cl |
| Synonyms | TAK659, TAK-659, TAK 659, TAK-659 2HCl, TAK659 dihydrochloride |
| Protocol | In Vitro | In vitro activity: 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. 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. Kinase Assay: TAK-659 hydrochloride is a potent, selective and orally available spleen tyrosine kinase (Syk) inhibitor with an IC50 of 3.2 nM. Cell Assay: Cells are maintained at 37°C in a humidified atmosphere containing 5-8% CO2. In a panel of hematological and solid tumor cell lines, inhibition of cell viability is determined using the soluble tetrazolium salt, MTS. Cells are seeded in 96-well tissue culture plates and are incubated at 37°C/5% CO2 for 24 hours prior to addition of compounds or DMSO vehicle. After 72 or 96 hours of incubation with compounds, MTS conversion by metabolically active cells is determined by measuring the OD490 nm of the wells using a Thermomax microplate reader. To generate concentration-response curves, cells are treated in duplicate with a range of serial compound dilutions. Prior to addition to cells, compound dilutions are prepared in DMSO. Equal amounts of DMSO are added to cells (final concentration is 0.5%). After background correction and normalization against DMSO-treated cells, EC50 values are calculated by curve-fitting these cell viability results using nonlinear regression analysis. |
|---|---|---|
| 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 | |
| Animal model | Athymic nude mice |
| Solvent volume to be added | Mass (the weight of a compound) | |||
|---|---|---|---|---|
| Mother liquor concentration | 1mg | 5mg | 10mg | 20mg |
| 1mM | 2.3963 mL | 11.9815 mL | 23.9630 mL | 47.9260 mL |
| 5mM | 0.4793 mL | 2.3963 mL | 4.7926 mL | 9.5852 mL |
| 10mM | 0.2396 mL | 1.1982 mL | 2.3963 mL | 4.7926 mL |
| 20mM | 0.1198 mL | 0.5991 mL | 1.1982 mL | 2.3963 mL |
This equation is commonly abbreviated as: C1 V1 = C2 V2
- (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
- (2) Be sure to add the solvent(s) in order.