General
Preferred name
asciminib
Synonyms
ABL001 ()
AY7 ()
ABL-001 ()
Asciminib (hydrochloride) ()
ABL001 (hydrochloride) ()
Asciminib (ABL001) ()
ABL-0013-Pyridinecarboxamide, N-[4-(chlorodifluoromethoxy)phenyl]-6-[(3R)-3-hydroxy-1-pyrrolidinyl]-5-(1H-pyrazol-3-yl)- ()
ASCIMINIB HYDROCHLORIDE ()
ABL001-NX ()
NVP-ABL001 ()
ABL001-AAA ()
Scemblix ()
P&D ID
PD047351
CAS
1492952-76-7
2119669-71-3
Tags
available
probe
drug
Approved by
EMA
PMDA
FDA
First approval
2020
2021
Drug indication
chronic myelogenous leukemia
Chronic myeloid leukaemia
acute lymphoblastic leukemia
Drug Status
approved
investigational
Max Phase
4.0
Probe info
Probe type
P&D approved
experimental probe
Probe selectivity
protein-selective
Probe sources
Probe targets
[[ compound.targets[t].gene_name ]]
Probe control
Probe control not defined
Orthogonal probes
50
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
COMMENT
ABL001 (Asciminib) is an allosteric inhibitor of ABL kinase, and binds the myristate pocket similar to previous generations of allosteric inhibitors such as GNF-2 and GNF-5. ABL001 is ~100-fold more potent than GNF-2, but retains exquisite selectivity for ABL kinase compared to other kinases and also outside the kinase family. This probe retains potency for inhibition of BCR-ABL even in the context of all catalytic site mutations including T315I. ABL001 is efficacious as a single agent for use in both cells and animal models, and is currently being explored in combinations with active site inhibitors such as nilotinib, imatinib, and dasatinib. It should provide a valuable tool to the field for the study of BCR-ABL in the context of CML. Reviewer Probe testing: ABL001 has been tested in our lab in the ABL1 NanoBRET TE assay using tracer K4. It demonstrated an IC50 of 2nM in HEK293 cells. This is consistent with recommended concentrations of up to 250nM. Jan 7 2021 - 11:33am; NMR and X-Ray crystallography studies confirmed that ABL001 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; GNF-2 displayed a profile analogous to ABL001 but is ~100-fold less potent. Jan 19 2021 - 12:26pm
DESCRIPTION
Asciminib (ABL001) is a negative allosteric modulator of BCR-ABL1 , that induces the kinase to adopt an autoinhibitory, and thereby inactive, conformation . The compound is the result of a structure-guided medicinal chemistry program targeting the vestigial myristoyl pocket of the ABL1 kinase. The acronym STAMP inhibitor is used to descrobe this class of compound, which specifically targets the ABL myristoyl pocket. The structure of ABL001 was disclosed at the American Society of Hematology's (ASH) 57th Annual Meeting and Exposition in Orlando, Florida (Dec., 2015)- see Abstract 1565. Mechanisms by which resistance to asciminib can develop are reported by Qiang et al. (2017) , including the development of T315I (confers resistance to )-inclusive compound mutations. Combining ponatinib + asciminib has been shown to be effective against such compound mutations .
Asciminib-based PROTACs have been reported . (GtoPdb)
Asciminib-based PROTACs have been reported . (GtoPdb)
DESCRIPTION
ABL001 is a negative allosteric modulator of BCR-ABL1 , that induces an autoinhibitory conformation. The compound is the result of a structure-guided medicinal chemistry program targeting the vestigial myristoyl pocket of the ABL1 kinase. The structure of AB001 was disclosed at the American Society of Hematology's (ASH) 57th Annual Meeting and Exposition in Orlando, Florida (Dec., 2015)- see Abstract 1565.
DESCRIPTION
Asciminib (ABL001) is a potent and selective allosteric BCR-ABL1 inhibitor, which inhibits Ba/F3 cells grown with an IC50 of 0.25 nM[1].
PRICE
183
DESCRIPTION
Asciminib (ABL001) (ABL001) is a potent and selective Bcr-Abl inhibitor (Kd: 0.5?C0.8nM).
DESCRIPTION
Asciminib (ABL001) hydrochloride is a potent and selective allosteric BCR-ABL1 inhibitor, which inhibits Ba/F3 cells grown with an IC50 of 0.25 nM[1].
MOA
Inhibitor
(Chemical Probes.org)
DESCRIPTION
On October 2021, FDA approved asciminib To treat Philadelphia chromosome-positive chronic myeloid leukemia with disease that meets certain criteria
(PKIDB)
DESCRIPTION
Asciminib (ABL001) (ABL001) is a potent and selective Bcr-Abl inhibitor (Kd: 0.5–0.8nM).
(TargetMol Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
2
Organisms
0
Compound Sets
20
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Chemical Probes.org
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
EUbOPEN Chemogenomics Library
Guide to Pharmacology
High-quality chemical probes
MedChem Express Bioactive Compound Library
NIH Approved Oncology Drugs
PKIDB
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
31
Molecular Weight
449.11
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
3
Rotatable Bonds
6
Ring Count
4
Aromatic Ring Count
3
cLogP
3.46
TPSA
103.37
Fraction CSP3
0.25
Chiral centers
1.0
Largest ring
6.0
QED
0.5
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
ABL1
Bcr-Abl
MOA
Bcr-Abl kinase inhibitor
Orthogonal probe
GNF-5
Target class
Protein kinase
Kinase
Pathway
Protein Tyrosine Kinase/RTK
Angiogenesis
Cytoskeletal Signaling
Tyrosine Kinase/Adaptors
Target subclass
TK
Recommended Cell Concentration
100 nM
Source data
