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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
Structure of ASCIMINIB

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

HIDE SMILES / InChI

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

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.

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P00519
Gene ID: 25
Gene Symbol: ABL1
Target Organism: Homo sapiens (Human)
1.30000000000000004 nM [IC50]
Conditions
PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

40 mg ABL001 twice a day administered in adult patients with Chronic Myelogenous Leukemia
Route of Administration: Oral
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 Sat Jun 26 01:28:46 UTC 2021
Edited
by admin
on Sat Jun 26 01:28:46 UTC 2021
Record UNII
L1F3R18W77
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ASCIMINIB
INN   WHO-DD  
USAN   INN  
Official Name English
ABL-001
Code English
ABL001
Code English
N-(4-(CHLORODIFLUOROMETHOXY)PHENYL)-6-((3R)-3- HYDROXYPYRROLIDIN-1-YL)-5-(1H-PYRAZOL-3-YL)PYRIDINE- 3-CARBOXAMIDE
Systematic Name English
ASCIMINIB [INN]
Common Name English
3-PYRIDINECARBOXAMIDE, N-(4-(CHLORODIFLUOROMETHOXY)PHENYL)-6-((3R)-3-HYDROXY-1-PYRROLIDINYL)-5-(1H-PYRAZOL-3-YL)-
Systematic Name English
NVP-ABL001
Code English
ABL001-NX
Code English
ASCIMINIB [USAN]
Common Name English
ASCIMINIB [WHO-DD]
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
FDA UNII
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
ChEMBL
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
NCI_THESAURUS
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
CAS
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
DRUG BANK
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
PUBCHEM
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
INN
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)