Details of the Drug

General Information of Drug (ID: DM7EVUF)

Drug Name

ABL001

Synonyms

asciminib; ABL-001; 1492952-76-7; Asciminib free base; ABL001-NX; UNII-L1F3R18W77; L1F3R18W77; NVP-ABL001; (R)-N-(4-(Chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)nicotinamide; 1492952-76-7 (free base); N-[4-[chloro(difluoro)methoxy]phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-5-yl)pyridine-3-carboxamide; Asciminib [USAN]; Asciminib (ABL001); Asciminib (USAN/INN); GTPL8962; CHEMBL4208229; SCHEMBL15388306; TQP0925; EX-A3030; BDBM50459091; NSC789925; s8555; ZINC150275965; CCG-269232; CS-7655; DB12597; NSC-789925; SB18878; BS-15538; HY-104010; D11403; Q27074535; (R)-N-(4-(Chloro difluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)nicotinamide; AY7

Indication

Disease Entry	ICD 11	Status	REF
Chronic myeloid leukaemia	2A20	Phase 3	[1]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

449.8

Topological Polar Surface Area (xlogp)

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 15112 mcgh/L [2]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 1781 mcg/L [2]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2.5 h [2]
Clearance: The clearance of drug is 6.7 L/h [2]
Elimination: Following oral administration, approximately 80% and 11% of an asciminib dose was recovered in the feces and urine, respectively [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 5.5 hours [2]
Metabolism: The drug is metabolized via the CYP3A4 [2]
Vd: The volume of distribution (Vd) of drug is 151 L [2]

Chemical Identifiers

Formula: C20H18ClF2N5O3
IUPAC Name: N-[4-[chloro(difluoro)methoxy]phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-5-yl)pyridine-3-carboxamide
Canonical SMILES: C1CN(C[C@@H]1O)C2=C(C=C(C=N2)C(=O)NC3=CC=C(C=C3)OC(F)(F)Cl)C4=CC=NN4
InChI: 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
InChIKey: VOVZXURTCKPRDQ-CQSZACIVSA-N

Cross-matching ID

PubChem CID: 72165228
CAS Number: 1492952-76-7
DrugBank ID: DB12597
TTD ID: DSHT18

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fusion protein Bcr-Abl (Bcr-Abl)	TTS7G69	BCR_HUMAN-ABL1_HUMAN	Inhibitor	[3]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

References

1	ClinicalTrials.gov (NCT03106779) Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs. U.S. National Institutes of Health.
2	FDA Approved Drug Products: Scemblix (asciminib) tablets for oral use
3	Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. N Engl J Med. 2019 Dec 12;381(24):2315-2326.
4	A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
5	2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
6	Danusertib, an aurora kinase inhibitor.Expert Opin Investig Drugs.2012 Mar;21(3):383-93.
7	ABL001, a Potent Allosteric Inhibitor of BCR-ABL, Prevents Emergence of Resistant Disease When Administered in Combination with Nilotinib in an in Vivo Murine Model of Chronic Myeloid Leukemia, NorthBuilding, 2014, 120-125.
8	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
9	Design, synthesis and preclinical evaluation of NRC-AN-019. Int J Oncol. 2013 Jan;42(1):168-78.
10	Preclinical development of HQP1351, a multikinase inhibitor targeting a broad spectrum of mutant KIT kinases, for the treatment of imatinib-resistant gastrointestinal stromal tumors. Cell Biosci. 2019 Oct 26;9:88.
11	NPB001-05 inhibits Bcr-Abl kinase leading to apoptosis of imatinib-resistant cells. Front Biosci (Elite Ed). 2011 Jun 1;3:1273-88.
12	Effects of the Bcr/abl kinase inhibitors STI571 and adaphostin (NSC 680410) on chronic myelogenous leukemia cells in vitro. Blood. 2002 Jan 15;99(2):664-71.