Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C20H18ClF2N5O3 |
Molecular Weight | 449.8391 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
c1cc(ccc1NC(=O)c2cc(-c3cc[nH]n3)c(nc2)N4CC[C@]([H])(C4)O)OC(Cl)(F)F
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 | 449.8391 |
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 |
|||
Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
Second line small molecule therapy options for treating chronic myeloid leukemia. | 2017 Jan |
|
The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. | 2017 Mar 30 |
|
Identification and characterization of activating ABL1 1b kinase mutations: impact on sensitivity to ATP-competitive and allosteric ABL1 inhibitors. | 2017 May |
Patents
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
by
admin
on
Edited
Sat Jun 26 01:28:46 UTC 2021
by
admin
on
Sat Jun 26 01:28:46 UTC 2021
|
Record UNII |
L1F3R18W77
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Code | English | ||
|
Code | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Code | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
NCI_THESAURUS |
C1967
Created by
admin on Sat Jun 26 01:28:46 UTC 2021 , Edited by admin on Sat Jun 26 01:28:46 UTC 2021
|
||
|
NCI_THESAURUS |
C129825
Created by
admin on Sat Jun 26 01:28:46 UTC 2021 , Edited by admin on Sat Jun 26 01:28:46 UTC 2021
|
||
|
FDA ORPHAN DRUG |
556416
Created by
admin on Sat Jun 26 01:28:46 UTC 2021 , Edited by admin on Sat Jun 26 01:28:46 UTC 2021
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
L1F3R18W77
Created by
admin on Sat Jun 26 01:28:46 UTC 2021 , Edited by admin on Sat Jun 26 01:28:46 UTC 2021
|
PRIMARY | |||
|
CHEMBL3545115
Created by
admin on Sat Jun 26 01:28:46 UTC 2021 , Edited by admin on Sat Jun 26 01:28:46 UTC 2021
|
PRIMARY | |||
|
C114494
Created by
admin on Sat Jun 26 01:28:46 UTC 2021 , Edited by admin on Sat Jun 26 01:28:46 UTC 2021
|
PRIMARY | |||
|
1492952-76-7
Created by
admin on Sat Jun 26 01:28:46 UTC 2021 , Edited by admin on Sat Jun 26 01:28:46 UTC 2021
|
PRIMARY | |||
|
DB12597
Created by
admin on Sat Jun 26 01:28:46 UTC 2021 , Edited by admin on Sat Jun 26 01:28:46 UTC 2021
|
PRIMARY | |||
|
72165228
Created by
admin on Sat Jun 26 01:28:46 UTC 2021 , Edited by admin on Sat Jun 26 01:28:46 UTC 2021
|
PRIMARY | |||
|
10267
Created by
admin on Sat Jun 26 01:28:46 UTC 2021 , Edited by admin on Sat Jun 26 01:28:46 UTC 2021
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
SALT/SOLVATE -> PARENT | |||
|
TARGET -> INHIBITOR |
ALLOSTERIC INHIBITOR
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
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)
|