Details of the Drug

General Information of Drug (ID: DMMZOYN)

Drug Name

ABT-348

Synonyms

ILORASERTIB; ABT-348; 1227939-82-3; UNII-6L5D03D975; ABT 348; ABT348; 6L5D03D975; A-968660; Abbott-969660; Ilorasertib [USAN:INN]; Ilorasertib (USAN); Kinome_405; GTPL9914; A-968660.0; SCHEMBL3381224; CHEMBL1980297; DTXSID10153718; WPHKIQPVPYJNAX-UHFFFAOYSA-N; BCP07256; ZINC63298074; BDBM50381716; SB16853; CS-6804; DB11694; KB-74395; HY-16018; US8722890, 1; Z-3287; US8722890, 2; D10423; N-(4-{4-amino-7-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl}phenyl)-N'-(3-fluorophenyl)urea

Indication

Disease Entry	ICD 11	Status	REF
Haematological malignancy	2B33.Y	Phase 2	[1]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

488.5

Topological Polar Surface Area (xlogp)

3

Rotatable Bond Count (rotbonds)

6

Hydrogen Bond Donor Count (hbonddonor)

4

Hydrogen Bond Acceptor Count (hbondacc)

7

Chemical Identifiers

Formula: C25H21FN6O2S
IUPAC Name: 1-[4-[4-amino-7-[1-(2-hydroxyethyl)pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl]phenyl]-3-(3-fluorophenyl)urea
Canonical SMILES: C1=CC(=CC(=C1)F)NC(=O)NC2=CC=C(C=C2)C3=CSC4=C3C(=NC=C4C5=CN(N=C5)CCO)N
InChI: InChI=1S/C25H21FN6O2S/c26-17-2-1-3-19(10-17)31-25(34)30-18-6-4-15(5-7-18)21-14-35-23-20(12-28-24(27)22(21)23)16-11-29-32(13-16)8-9-33/h1-7,10-14,33H,8-9H2,(H2,27,28)(H2,30,31,34)
InChIKey: WPHKIQPVPYJNAX-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 46207586
CAS Number: 1227939-82-3
DrugBank ID: DB11694
TTD ID: D08HOM

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aurora kinase A (AURKA)	TTPS3C0	AURKA_HUMAN	Modulator	[2]
Aurora kinase B (AURKB)	TT5LS6T	AURKB_HUMAN	Modulator	[2]
Aurora kinase C (AURKC)	TTLYXIT	AURKC_HUMAN	Modulator	[2]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Haematological malignancy

ICD Disease Classification

2B33.Y

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Aurora kinase A (AURKA)	DTT	AURKA	9.41E-46	-1.78	-2.05
Aurora kinase B (AURKB)	DTT	AURKB	3.52E-36	-0.82	-1.62

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	ClinicalTrials.gov (NCT02478320) Phase II Study of Ilorasertib (ABT348) in Patients With CDKN2A Deficient Solid Tumors.
2	Preclinical characterization of ABT-348, a kinase inhibitor targeting the aurora, vascular endothelial growth factor receptor/platelet-derived growth factor receptor, and Src kinase families. J Pharmacol Exp Ther. 2012 Dec;343(3):617-27.
3	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.
4	A phase I trial of AT9283 (a selective inhibitor of aurora kinases) in children and adolescents with solid tumors: a Cancer Research UK study. Clin Cancer Res. 2015 Jan 15;21(2):267-73.
5	Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
6	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1936).
7	Clinical pipeline report, company report or official report of Cyclacel.
8	Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res. 2010 Dec 1;70(23):9846-54.
9	SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.
10	doi: 10.1158/1535-7163.TARG-13-B281
11	Preclinical characterization of Aurora kinase inhibitor R763/AS703569 identified through an image-based phenotypic screen. J Cancer Res Clin Oncol. 2010 Jan;136(1):99-113.
12	Effect of Aurora A kinase inhibitor MLN8237 combined with rituximab on antitumor activity in preclinical B-cell non-Hodgkin's lymphoma models. Journal of Clinical Oncology, 2009:8553.
13	Aurora A-Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy. Mol Cancer Ther. 2019 Dec;18(12):2207-2219.
14	Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem. 2005 Apr 21;48(8):3080-4.
15	Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. J Med Chem. 2010 May 27;53(10):3973-4001.
16	Clinical experience with aurora kinase inhibitors: a review. Oncologist. 2009 Aug;14(8):780-93.
17	An integrated computational approach to the phenomenon of potent and selective inhibition of aurora kinases B and C by a series of 7-substituted in... J Med Chem. 2007 Aug 23;50(17):4027-37.
18	The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.