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Asciminib (ABL001) (Synonyms: ABL001)

カタログ番号GC32703

Asciminib (ABL001) (ABL001) は強力かつ選択的なアロステリック BCR-ABL1 阻害剤であり、0.25 nM の IC50 で成長した Ba/F3 細胞を阻害します。

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Asciminib (ABL001) 化学構造

Cas No.: 1492952-76-7

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1mg
$35.00
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5mg
$77.00
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10mg
$119.00
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25mg
$245.00
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50mg
$385.00
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100mg
$595.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment:

Ba/F3 cells are treated with a range concentration of asciminib (0-10000 nM) for 48 h. Cell proliferation is measured using the Britelite luciferase detection assay[1].

Animal experiment:

Mice: Asciminib efficacy in three patient-derived ALL systemic xenograft models (ALL-7015, AL-7119 and AL-7155) is assessed by FACS monitoring of the percentage of CD45+ cells per live cell in blood samples taken at varying time points after dosing with either 7.5 mg/kg BID (group 2) or 30 mg/kg BID (group 3) asciminib for 3 weeks[1].

References:

[1]. Wylie AA, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. Nature. 2017 Mar 30;543(7647):733-737.

Background

Asciminib (ABL001) is a potent and selective allosteric Bcr-Abl inhibitor; inhibits Ba/F3 cells grown with an IC50 of 0.25 nM.

Asciminib binds to the myristoyl pocket of ABL1 and induces the formation of an inactive kinase conformation. NMR and biophysical studies confirm that asciminib binds potently (dissociation constant=0.5-0.8nM) and selectively to the myristoyl pocket of ABL1 and induces the inactive C-terminal helix conformation. Asciminib binding mimics the structural consequences of myristate binding to the N terminus of ABL1. Consistent with this binding site, asciminib exhibits the same non-ATP-competitive biochemical kinetics as the BCR-ABL inhibitor GNF-2 but with approximately 100-fold greater potency. Asciminib lacks activity against more than 60 kinases, including SRC, and is similarly inactive against G-protein-coupled receptors, ion channels, nuclear receptors and transporters. In BCR-ABL1-transformed Ba/F3 cells grown without IL-3, asciminib has an anti-proliferative with IC50 value of 0.25nM. In the CML blast-phase cell line KCL-22, asciminib inhibits phosphorylation of both STAT5 (Tyr694; pSTAT5) and BCR-ABL1 (Tyr245; pBCR-ABL1) after 1h using concentrations that correlate with those required for inhibition of cell proliferation. Asciminib is selectively active against all BCR-ABL1 lines (IC50 value of 1-20nM), irrespective of the presence of either the p210 or the p190 BCR-ABL1 isoform.[1].

Asciminib is undergoing clinical development testing in patients with CML and Philadelphia chromosome-positive acute lymphoblastic leukaemia. Single doses of 7.5, 15 and 30 mg/kg ABL001, administered to mice bearing KCL- 22 xenografts, inhibits pSTAT5 (Tyr694), which return to baseline at 10, 12 and 16-20h after administration of the dose, respectively. In mice implanted with KCL-22 tumors, the minimum dose of asciminib required for complete regression is 7.5 mg/kg twice a day (BID) or 30 mg/kg once a day (QD), and is tolerated at doses up to 250 mg/kg BID. Similarly, in xenografts derived from patients, treatment with 7.5 and 30 mg/kg asciminib leads to regressions that are maintained during dosing[1].

[1]. Wylie AA, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. Nature. 2017 Mar 30;543(7647):733-737.

Chemical Properties

Cas No. 1492952-76-7 SDF
同義語 ABL001
Canonical SMILES O=C(C1=CC(C2=NNC=C2)=C(N3C[C@H](O)CC3)N=C1)NC4=CC=C(OC(F)(Cl)F)C=C4
Formula C20H18ClF2N5O3 M.Wt 449.84
溶解度 DMSO : ≥ 100 mg/mL (222.30 mM) Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 2.223 mL 11.1151 mL 22.2301 mL
5 mM 0.4446 mL 2.223 mL 4.446 mL
10 mM 0.2223 mL 1.1115 mL 2.223 mL
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Review for Asciminib (ABL001)

Average Rating: 5 ★★★★★ (Based on Reviews and 21 reference(s) in Google Scholar.)

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