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| Size | Price | Stock |
|---|---|---|
| 500mg | $630 | Check With Us |
| 1g | $1030 | Check With Us |
| 5g | $2600 | Check With Us |
: Cat #: V5145 CAS #: 1132827-21-4 Purity ≥ 98%
Description: Quizartinib HCl (formerly AC220 and AC010220) is a novel, second-generation, and orally bioavailable FLT3 tyrosine kinase inhibitor for Flt3 (ITD/WT) with IC50 of 1.1 nM/4.2 nM in MV4-11 and RS4;11 cells, respectively, 10-fold more selective for Flt3 than KIT, PDGFRα, PDGFRβ, RET, and CSF-1R. Quizartinib has displayed potential anticancer activity. AC220 selectively inhibits class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (FLT3/STK1), colony-stimulating factor 1 receptor (CSF1R/FMS), stem cell factor receptor (SCFR/KIT), and platelet derived growth factor receptors (PDGFRs), resulting in inhibition of ligand-independent leukemic cell proliferation and apoptosis. Mutations in FLT3, resulting in constitutive activation, are the most frequent genetic alterations in acute myeloid leukemia (AML) and occur in approximately one-third of AML cases.
References: Blood. 2009 Oct 1;114(14):2984-92.
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| Molecular Weight (MW) | 633.59 |
|---|---|
| Molecular Formula | C29H34Cl2N6O4S |
| CAS No. | 1132827-21-4 |
| Storage | -20℃ for 3 years in powder formr |
| -80℃ for 2 years in solvent | |
| Solubility In Vitro | DMSO: 33.2 mg/mL (59.2 mM)r |
| Water: <1 mg/mLr | |
| Ethanol: <1 mg/mL | |
| Solubility In Vivo | 15% Captisol: 30 mg/mL |
| SMILES Code | O=C(NC1=CC=C(C(N=C2SC3=C4)=CN2C3=CC=C4OCCN5CCOCC5)C=C1)NC6=NOC(C(C)(C)C)=C6 |
| Synonyms | AC220 HCl or AC010220 HCl; AC220 diHCl; AC 220; AC-220 dihydrochloride; AC010220; AC-010220; AC 010220; AC010220 |
| Protocol | In Vitro | In vitro activity: AC220, a unique, potent and selective inhibitor of FLT3, has high affinity for FLT3 with a Kd value of 1.6 nM. AC220 inhibits the autophosphorylation of FLT3 in the human leukemia cell lines MV4-11 which harbor a homozygous FLT3-ITD mutation and is FLT3 dependent, and RS4;11 which expresses wild-type FLT3 with IC50 values of 1.1 nM and 4.2 nM, respectively. AC220 is the most potent cellular FLT3-ITD inhibitor, leading to the most significant inhibition of MV4-11 cell proliferation with IC50 of 0.56 nM compared to all other FLT3 inhibitors whose IC50 values range from 0.87 nM to 64 nM. AC220 has no inhibitory activity against the proliferation of A375 cells which harbor an activating mutation in BRAF and are not FLT3 dependent, indicating a large window between FLT3 inhibition and general cytotoxic effects. Kinase Assay: To measure inhibition of FLT3 autophosphorylation, MV4-11 or RS4;11 cells are cultured in low serum media (0.5% FBS) overnight and seeded at a density of 400 000 cells per well in a 96-well plate the following day. The cells are incubated with different concentrations of AC220 for 2 hours at 37 °C. To induce FLT3 autophosphorylation in RS4;11 cells, 100 ng/mL FLT3 ligand is added for 15 minutes after the 2-hour AC220 incubation. Cell lysates are prepared and incubated in 96-well plates precoated with a total FLT3 capture antibody. The coated plates are incubated with either a biotinylated antibody against FLT3 to detect total FLT3 or an antibody against phosphotyrosines to detect FLT3 autophosphorylation. In both cases, a SULFO-tagged streptavidin secondary antibody is used for electrochemiluminescence detection on the Meso Scale Discovery platform. The concentration of AC220 that inhibits FLT3-ITD or TLT3-WT autophosphorylation by 50% represents IC50 value. Cell Assay: Cells (MV4-11 and RS4;11 cells) are cultured overnight in low serum media (0.5% FBS), seeded in a 96-well plate at 40 000 cells per well and exposed to AC220 for 72 hours at 37 °C. Cell viability is measured using the Cell Titer-Blue Cell Viability Assay. |
|---|---|---|
| In Vivo | Oral administration of AC220 (10 mg/kg) induces time-dependent inhibition of FLT3 autophosphorylation in the FLT3-ITD–dependent MV4-11 tumor xenograft mouse model; the inhibition being 90% at 2 hours and 40% at 24 hours. AC220 significantly extends survival in a mouse model of FLT3-ITD AML with doses as low as 1 mg/kg given orally once a day. Treatment with AC220 at 10 mg/kg for 28 days results in rapid and complete regression of tumors in all mice with no tumor regrowth during the 60-day posttreatment period. AC220 displays more significant efficacy compared to sunitinib treatment which causes tumors to shrink slowly and resume growth immediately upon discontinuation of treatment in all but one of the mice. | |
| Animal model | Female NU/NU or severe combined immunodeficient mice implanted with MV4-11 cells | |
| Formulation | Formulated in 22% hydroxypropyl-β-cyclodextrin | |
| Dosages | 10 mg/kg; Oral gavage |
| Solvent volume to be added | Mass (the weight of a compound) | |||
|---|---|---|---|---|
| Mother liquor concentration | 1mg | 5mg | 10mg | 20mg |
| 1mM | 1.5783 mL | 7.8915 mL | 15.7831 mL | 31.5662 mL |
| 5mM | 0.3157 mL | 1.5783 mL | 3.1566 mL | 6.3132 mL |
| 10mM | 0.1578 mL | 0.7892 mL | 1.5783 mL | 3.1566 mL |
| 20mM | 0.0789 mL | 0.3946 mL | 0.7892 mL | 1.5783 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.