Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C20H18ClF2N5O3 |
Molecular Weight | 449.838 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O[C@@H]1CCN(C1)C2=C(C=C(C=N2)C(=O)NC3=CC=C(OC(F)(F)Cl)C=C3)C4=CC=NN4
InChI
InChIKey=VOVZXURTCKPRDQ-CQSZACIVSA-N
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
Molecular Formula | C20H18ClF2N5O3 |
Molecular Weight | 449.838 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/28329763
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28329763
ABL-001 (asciminib), a potent and selective allosteric tyrosine-protein kinase ABL1 inhibitor that is undergoing clinical development testing in patients with Chronic myeloid leukemia (CML) and Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia. is a tyrosine-protein kinase ABL1 inhibitor. In contrast to catalytic-site ABL1 kinase inhibitors, ABL001 binds to the myristoyl pocket of ABL1 and induces the formation of an inactive kinase conformation. ABL001 and second-generation catalytic inhibitors have similar cellular potencies but distinct patterns of resistance mutations, with genetic barcoding studies revealing pre-existing clonal populations with no shared resistance between ABL001 and the catalytic inhibitor nilotinib. ABL001 was tested on mice with a particularly aggressive type of CML. The combination of ABL001 and nilotinib led to complete disease control and eradicated CML xenograft tumors without recurrence after the cessation of treatment. ABL001 is being tested in clinical trials for treatment of CML and Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia alone and in combination with niotinib, imatinib or dasatinib.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P00519 Gene ID: 25.0 Gene Symbol: ABL1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/28329763 |
1.3 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Sample Use Guides
40 mg ABL001 twice a day administered in adult patients with Chronic Myelogenous Leukemia
Route of Administration:
Oral
In Vitro Use Guide
Sources: http://www.bloodjournal.org/content/128/22/2747
BL001 potently inhibited the proliferation of Ba/F3 cells expressing native BCR-ABL1 or a variety of BCR-ABL1 point mutations (IC50 range: 1.3-113.5 nM), with no observed toxicity to parental Ba/F3 cells up to 10 uM. Interestingly, however, ABL001 demonstrated little to no activity against a small panel of BCR-ABL1 compound mutations tested (G250E/T315I, E255K/T315I, E255V/T315I).
Substance Class |
Chemical
Created
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Edited
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Record UNII |
L1F3R18W77
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Record Status |
Validated (UNII)
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NCI_THESAURUS |
C1967
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FDA ORPHAN DRUG |
556416
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C129825
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Related Record | Type | Details | ||
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SALT/SOLVATE -> PARENT | |||
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TARGET -> INHIBITOR |
ALLOSTERIC INHIBITOR
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ACTIVE MOIETY |
Originator: Novartis; Developer: Novartis Oncology; Class: Anti-neoplastic, Small molecule; Mechanism of Action: Bcr-abl tyrosine kinase inhibitor; Orphan Drug Status: No; On Fast track: No; New Molecular Entity: Yes; Highest Development Phases: Phase I for Acute lymphoblastic leukaemia, Chronic myeloid leukaemia; Most Recent Events: 30 Apr 2014 Phase-I clinical trials in Chronic myeloid leukaemia (Second-line therapy or greater) in Australia, Germany, the Netherlands, Japan and South Korea (PO), 30 Apr 2014 Phase-I clinical trials in Acute lymphoblastic leukaemia (Second-line therapy or greater) in Australia, Germany, the Netherlands, Japan and South Korea (PO), 05 Mar 2014 Novartis plans a phase I trial for Chronic myeloid leukaemia & Acute lymphoblastic leukaemia in USA, Australia, Germany, France, Italy, the Netherlands, Spain, Japan, South Korea & Singapore (NCT02081378)
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