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Activity Type | Activity Value -log(M) | Mechanism of Action | Activity Reference | Publications (PubMed IDs) |
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SKU | Size | Availability | Price | Qty |
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A414054-5mg | 5mg | In stock | $168.90 | |
A414054-10mg | 10mg | In stock | $266.90 | |
A414054-25mg | 25mg | In stock | $432.90 | |
A414054-50mg | 50mg | In stock | $597.90 | |
A414054-100mg | 100mg | Available within 4-8 weeks(?) Items will be manufactured post-order and can take 4-8 weeks. Thank you for your patience! | $1,033.90 |
Abl Selective Inhibitors
Synonyms | asciminib|1492952-76-7|ABL-001|ABL001|ABL001-NX|Asciminib free base|NVP-ABL001|Example 9|Asciminib [USAN]|L1F3R18W77|UNII-L1F3R18W77|(R)-N-(4-(Chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)nicotinamide|1492952-76-7 (free ba |
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Specifications & Purity | Moligand™, ≥98% |
Biochemical and Physiological Mechanisms | Asciminib (ABL001) is a potent and selective allosteric ABL1 inhibitor with dissociation constant (Kd) of\u20090.5-0.8\u2009nM and selectivity to the myristoyl pocket of ABL1. |
Storage Temp | Store at -20°C |
Shipped In | Ice chest + Ice pads |
Grade | Moligand™ |
Action Type | ALLOSTERIC MODULATOR, INHIBITOR |
Mechanism of action | Tyrosine-protein kinase ABL inhibitor |
Product Description | Information Asciminib (ABL001) is a potent and selective allostericABL1inhibitor with dissociation constant (Kd) of 0.5-0.8 nM and selectivity to the myristoyl pocket of ABL1. Targets Abl1 (Cell-free assay) 0.45 nM In vitro ABL001 is a potent, selective BCR-ABL inhibitor that maintains activity across most mutations, including T315I, with a distinct, allosteric mechanism of action. ABL001 binds at a regulatory site typically occupied by a myristoyl group in wild-type ABL and inhibits ABL kinase activity through a mechanism distinct from catalytic site inhibitors. It binds to a pocket on the BCR-ABL kinase domain that is normally occupied by the myristoylated N-terminus of ABL1. Upon fusion with BCR, this myristoylated N-terminus that serves to autoregulate ABL1 activity is lost. ABL001 functionally mimics the role of the myristoylated N-terminus by occupying its vacant binding site and restores the negative regulation of the kinase activity. ABL001 selectively inhibits the growth of chronic myelogenous leukemia (CML) and Ph+ ALL cells with potencies ranging from 1-10 nM range while BCR-ABL-negative cell lines remained unaffected at concentrations 1000-fold higher. NMR and biophysical studies confirm that ABL001 binds potently (dissociation constant (Kd)\u2009=\u20090.5-0.8\u2009nM) and selectively to the myristoyl pocket of ABL1 and induces the inactive C-terminal helix conformation. ABL001 lacks activity against more than 60 kinases, including SRC and is similarly inactive against G-protein-coupled receptors, ion channels, nuclear receptors and transporters. Thus, ABL001 has high selectivity. In vivo In the KCL-22 mouse xenograft model, ABL001 displays potent anti-tumor activity with complete tumor regression observed and a clear dose-dependent correlation with pSTAT5 inhibition. ABL001 has moderate oral absorption, volume of distribution and half-life across all species. It as a single agent induces clinical anti-tumour activity and is well tolerated to date in a heavily pre-treated subgroup of patients with chronic myelogenous leukemia. As for the pharmacokinetics, pharmacodynamics and efficacy of ABL001, The CL (clearance) are 12, 16 and 6 mL/min/kg in mice, rats and dogs after a sigle iv dose of 1mg/kg, 2mg/kg and 1mg/kg, respectively. In mouse and dog, the T1/2term are 1.1 and 3.7 h after a single i.v. dose at 1 mg/kg. In Rat, theT1/2term is 2.7 h after a single i.v. dose at 2 mg/kg. The oral bioavailability of ABL001 in mouse and rat are 35% and 27% respectively when dosed at 30 mg/kg p.o. While in dogs the oral BA of ABL001 is 111% (15 mg/kg, p.o). Cell Research(from reference) Cell lines:KCL-22 cells Concentrations:0-250 nM Incubation Time:1\u2009h |
ALogP | 4.196 |
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HBD Count | 3 |
Rotatable Bond | 6 |
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IUPAC Name | N-[4-[chloro(difluoro)methoxy]phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-5-yl)pyridine-3-carboxamide |
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INCHI | InChI=1S/C20H18ClF2N5O3/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)/t14-/m1/s1 |
InChi Key | VOVZXURTCKPRDQ-CQSZACIVSA-N |
Canonical SMILES | C1CN(CC1O)C2=C(C=C(C=N2)C(=O)NC3=CC=C(C=C3)OC(F)(F)Cl)C4=CC=NN4 |
Isomeric 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 |
PubChem CID | 72165228 |
Molecular Weight | 449.84 |
PubChem CID | 72165228 |
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CAS Registry No. | 1492952-76-7 |
RCSB PDB Ligand | AY7 |
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Lot Number | Certificate Type | Date | Item |
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K2219027 | Certificate of Analysis | Sep 05, 2022 | A414054 |
K2219029 | Certificate of Analysis | Sep 05, 2022 | A414054 |
K2219030 | Certificate of Analysis | Sep 05, 2022 | A414054 |
K2219031 | Certificate of Analysis | Sep 05, 2022 | A414054 |
K2219032 | Certificate of Analysis | Sep 05, 2022 | A414054 |
Solubility | Solubility (25°C) In vitro DMSO: 89 mg/mL (197.84 mM); Ethanol: 89 mg/mL (197.84 mM); Water: Insoluble; |
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DMSO(mg / mL) Max Solubility | 89 |
DMSO(mM) Max Solubility | 197.8481238 |
1. Wylie AA, Schoepfer J, Jahnke W, Cowan-Jacob SW, Loo A, Furet P, Marzinzik AL, Pelle X, Donovan J, Zhu W et al.. (2017) The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1.. Nature, 543 (7647): (733-737). [PMID:28329763] |
2. Rea D, Mauro MJ, Boquimpani C, Minami Y, Lomaia E, Voloshin S, Turkina AG, Kim DW, Apperley JF, Abdo A et al.. (2021) A Phase 3, Open-Label, Randomized Study of Asciminib, a STAMP Inhibitor, vs Bosutinib in CML After ≥2 Prior TKIs.. Blood, 129 (3): (589-97). [PMID:34407542] |
3. Qiang W, Antelope O, Zabriskie MS, Pomicter AD, Vellore NA, Szankasi P, Rea D, Cayuela JM, Kelley TW, Deininger MW et al.. (2017) Mechanisms of resistance to the BCR-ABL1 allosteric inhibitor asciminib.. Leukemia, 31 (12): (2844-2847). [PMID:28819281] |
4. Nesr G, Laffan M, Claudiani S, Innes A, Apperley J, Milojkovic D. (2020) Platelet function in patients with chronic myeloid leukemia treated with asciminib.. Leuk Lymphoma, 61 (12): (3021-3023). [PMID:32654575] |
5. Yang Y, Gao H, Sun X, Sun Y, Qiu Y, Weng Q, Rao Y. (2020) Global PROTAC Toolbox for Degrading BCR-ABL Overcomes Drug-Resistant Mutants and Adverse Effects.. J Med Chem, 63 (15): (8567-8583). [PMID:32657579] |
6. El Rashedy AA, Olotu FA, Soliman MES. (2018) Dual Drug Targeting of Mutant Bcr-Abl Induces Inactive Conformation: New Strategy for the Treatment of Chronic Myeloid Leukemia and Overcoming Monotherapy Resistance.. Chem Biodivers, 15 (3): (e1700533). [PMID:29325229] |
7. Manley PW, Barys L, Cowan-Jacob SW. (2020) The specificity of asciminib, a potential treatment for chronic myeloid leukemia, as a myristate-pocket binding ABL inhibitor and analysis of its interactions with mutant forms of BCR-ABL1 kinase.. Leuk Res, 98 (3): (106458). [PMID:33096322] |
8. Schoepfer J, Jahnke W, Berellini G, Buonamici S, Cotesta S, Cowan-Jacob SW, Dodd S, Drueckes P, Fabbro D, Gabriel T et al.. (2018) Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1.. J Med Chem, 61 (18): (8120-8135). [PMID:30137981] |
9. Gleixner KV, Filik Y, Berger D, Schewzik C, Stefanzl G, Sadovnik I, Degenfeld-Schonburg L, Eisenwort G, Schneeweiss-Gleixner M, Byrgazov K et al.. (2021) Asciminib and ponatinib exert synergistic anti-neoplastic effects on CML cells expressing BCR-ABL1 T315I-compound mutations.. Am J Cancer Res, 11 (9): (4470-4484). [PMID:34659899] |