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Asciminib HCl (ABL001; ABL-001; Scemblix), the hydrochloride version of Asciminib, is an allosteric inhibitor of BCR-ABL1 that was approved by the FDA on October 29, 2021, for the treatment of chronic myeloid leukemia (CML) with the Philadelphia chromosome.
| ln Vitro |
Asciminib (ABL001) hydrochloride attaches itself to ABL1's myristoyl pocket and causes the kinase conformation to become inactive[1].
Asciminib hydrochloride selectively and potently binds to the myristoyl pocket of ABL1 to induce the inactive C-terminal helix conformation (dissociation constant: 0.5-0.8 nM). With about 100 times more potency, asciminib hydrochloride displays the same non-ATP-competitive biochemical kinetics as the BCR-ABL inhibitor GNF-2[1]. Asciminib hydrochloride is inactive against G-protein-coupled receptors, ion channels, nuclear receptors, and transporters, as well as more than 60 kinases, including SRC[1]. Asciminib hydrochloride has an IC50 value of 0.25 nM for anti-proliferative activity in BCR-ABL1-transformed Ba/F3 cells grown without IL-3. Once one hour has passed, asciminib hydrochloride, at concentrations correlated with those needed to inhibit cell proliferation, phosphorylates both STAT5 (Tyr694; pSTAT5) and BCR–ABL1 (Tyr245; pBCR–ABL1) in the CML blast-phase cell line KCL-22[1]. Asciminib hydrochloride is specifically active against every BCR-ABL1 line (IC50 value of 1–20 nM), regardless of whether the p210 or p190 BCR–ABL1 isoform is present[1]. |
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| ln Vivo |
Asciminib must be administered to mice implanted with KCL-22 tumors at least 7.5 mg/kg twice daily (BID) or 30 mg/kg once daily (QD) for complete regression. Doses up to 250 mg/kg BID are tolerated[1]. Mice carrying KCL- 22 xenografts receive single doses of Asciminib at7.5,15, and 30 mg/kg, which inhibit pSTAT5 (Tyr694). The dose-reversal occurs 10, 12, and 16–20 hours after the initial administration.
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| References |
| Molecular Formula |
C20H19CL2F2N5O3
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|---|---|
| Molecular Weight |
486.3
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| Exact Mass |
485.0833
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| Elemental Analysis |
C, 49.40; H, 3.94; Cl, 14.58; F, 7.81; N, 14.40; O, 9.87
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| CAS # |
2119669-71-3
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| Related CAS # |
Asciminib;1492952-76-7
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| Appearance |
Solid powder
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| SMILES |
C1CN(C[C@@H]1O)C2=C(C=C(C=N2)C(=O)NC3=CC=C(C=C3)OC(F)(F)Cl)C4=CC=NN4.Cl
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| InChi Key |
HGCOOPLEWPBLOY-PFEQFJNWSA-N
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| InChi Code |
InChI=1S/C20H18ClF2N5O3.ClH/c21-20(22,23)31-15-3-1-13(2-4-15)26-19(30)12-9-16(17-5-7-25-27-17)18(24-10-12)28-8-6-14(29)11-28;/h1-5,7,9-10,14,29H,6,8,11H2,(H,25,27)(H,26,30);1H/t14-;/m1./s1
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| Chemical Name |
N-[4-[chloro(difluoro)methoxy]phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-5-yl)pyridine-3-carboxamide;hydrochloride
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| Synonyms |
asciminib; Asciminib hydrochloride; ABL-001; ABL001; AB -001; ABL001-AAA
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~205.6 mM)
H2O: <0.1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.14 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.14 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.14 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0563 mL | 10.2817 mL | 20.5634 mL | |
| 5 mM | 0.4113 mL | 2.0563 mL | 4.1127 mL | |
| 10 mM | 0.2056 mL | 1.0282 mL | 2.0563 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(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.
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