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Details

Stereochemistry ABSOLUTE
Molecular Formula C20H18ClF2N5O3.ClH
Molecular Weight 486.299
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ASCIMINIB HYDROCHLORIDE

SMILES

Cl.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=HGCOOPLEWPBLOY-PFEQFJNWSA-N
InChI=1S/C20H18ClF2N5O3.ClH/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);1H/t14-;/m1./s1

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

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

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P00519
Gene ID: 25.0
Gene Symbol: ABL1
Target Organism: Homo sapiens (Human)
1.3 nM [IC50]
Conditions

Conditions

PubMed

PubMed

TitleDatePubMed
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
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 Dec 16 14:44:59 UTC 2023
Edited
by admin
on Sat Dec 16 14:44:59 UTC 2023
Record UNII
C5U34S9XFV
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ASCIMINIB HYDROCHLORIDE
USAN  
Official Name English
ASCIMINIB HYDROCHLORIDE [USAN]
Common Name English
ASCIMINIB HYDROCHLORIDE [JAN]
Common Name English
ABL001-AAA
Code English
Asciminib hydrochloride [WHO-DD]
Common Name English
ASCIMINIB HYDROCHLORIDE [ORANGE BOOK]
Common Name English
SCEMBLIX
Brand Name English
Code System Code Type Description
SMS_ID
300000011169
Created by admin on Sat Dec 16 14:44:59 UTC 2023 , Edited by admin on Sat Dec 16 14:44:59 UTC 2023
PRIMARY
USAN
FG-585
Created by admin on Sat Dec 16 14:44:59 UTC 2023 , Edited by admin on Sat Dec 16 14:44:59 UTC 2023
PRIMARY
FDA UNII
C5U34S9XFV
Created by admin on Sat Dec 16 14:44:59 UTC 2023 , Edited by admin on Sat Dec 16 14:44:59 UTC 2023
PRIMARY
DAILYMED
C5U34S9XFV
Created by admin on Sat Dec 16 14:44:59 UTC 2023 , Edited by admin on Sat Dec 16 14:44:59 UTC 2023
PRIMARY
RXCUI
2584303
Created by admin on Sat Dec 16 14:44:59 UTC 2023 , Edited by admin on Sat Dec 16 14:44:59 UTC 2023
PRIMARY
PUBCHEM
133082086
Created by admin on Sat Dec 16 14:44:59 UTC 2023 , Edited by admin on Sat Dec 16 14:44:59 UTC 2023
PRIMARY
NCI_THESAURUS
C171722
Created by admin on Sat Dec 16 14:44:59 UTC 2023 , Edited by admin on Sat Dec 16 14:44:59 UTC 2023
PRIMARY
CAS
2119669-71-3
Created by admin on Sat Dec 16 14:44:59 UTC 2023 , Edited by admin on Sat Dec 16 14:44:59 UTC 2023
PRIMARY
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