CAS 898280-07-4|XL228

Introduction：Basic information about CAS 898280-07-4|XL228, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. XL228 BiologicalActivity
3. Chemical & Physical Properties
4. Synonyms

Common Name	XL228
CAS Number	898280-07-4	Molecular Weight	437.541
Density	1.3±0.1 g/cm3	Boiling Point	715.7±70.0 °C at 760 mmHg
Molecular Formula	C₂₂H₃₁N₉O	Melting Point	/
MSDS	/	Flash Point	386.6±35.7 °C

Names

Name	4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine
Synonym	More Synonyms

XL228 BiologicalActivity

Description	XL228 is a multi-targeted tyrosine kinase inhibitor with IC50s of 5, 3.1, 1.6, 6.1, 2 nM for Bcr-Abl, Aurora A, IGF-1R, Src and Lyn, respectively.
Related Catalog	Signaling Pathways >>Protein Tyrosine Kinase/RTK >>Bcr-AblSignaling Pathways >>Protein Tyrosine Kinase/RTK >>IGF-1RSignaling Pathways >>Protein Tyrosine Kinase/RTK >>SrcResearch Areas >>Cancer
Target	Aurora A:3.1 nM (IC50) IGF-1R:1.6 nM (IC50)
In Vitro	XL228 shows a broad pattern of protein kinase inhibition, including the tyrosine kinases IGF1R, SRC, ABL, FGFR1‐3, and ALK and the serine/threonine kinases Aurora A and Aurora B. A panel of kinase inhibitors including XL228 is profiled against a series of cancer cell lines with known alterations in major signaling pathways. Approximately 30% of the lines demonstrate XL228 IC50 values of <100nM in viability assays, including many lines with characterized ALK or FGFR mutations or amplifications. XL228 eliminates the phosphorylation of Aurora A and B at concentrations above 10 nM. Short‐term treatment of HeLa cells leads to disruption of mitotic spindle formation, with the majority of mitotic cells exhibiting a unipolar spindle and disorganized chromosomes[2]. It displays low nanomolar biochemical activity against wild type Abl kinase (Ki=5 nM), as well as the T315I form of Abl resistant to imatinib and dasatinib (Ki=1.4 nM). XL228 inhibits phosphorylation of BCR-ABL and its substrate STAT5 in K562 cells in vitro with IC50s of 33 and 43 nM, respectively[3].
In Vivo	Single-dose pharmacodynamics studies demonstrate a potent effect of XL228 on BCR-ABL signaling in K562 xenograft tumors. Phosphorylation of BCR-ABL is decreased by 50% at XL228 plasma concentrations of 3.5 μM; a similar decrease in phospho-STAT5 occurred at 0.8 μM plasma concentration[3].
References	[1]. Cortes J, et al. Preliminary Clinical Activity in a Phase I Trial of the BCR-ABL/IGF- 1R/Aurora Kinase Inhibitor XL228 in Patients with Ph++ Leukemias with Either Failure to Multiple TKI Therapies or with T315I Mutation. Blood 2008 112:3232 [2]. Douglas O, et al. Abstract C192: Characterization of the target profile of XL228, a multi‐targeted protein kinase inhibitor in phase 1 clinical development. Mol Cancer Ther 2009;8(12 Suppl):C192. [3]. Shah N, et al. Targeting Drug-Resistant CML and Ph+-ALL with the Spectrum Selective Protein Kinase Inhibitor XL228. Blood 2007 110:474;

Chemical & Physical Properties

Density	1.3±0.1 g/cm3
Boiling Point	715.7±70.0 °C at 760 mmHg
Molecular Formula	C₂₂H₃₁N₉O
Molecular Weight	437.541
Flash Point	386.6±35.7 °C
Exact Mass	437.265167
PSA	117.49000
LogP	1.35
Vapour Pressure	0.0±2.3 mmHg at 25°C
Index of Refraction	1.669
InChIKey	ALKJNCZNEOTEMP-UHFFFAOYSA-N
SMILES	CC(C)c1cc(CNc2nc(Nc3cc(C4CC4)[nH]n3)cc(N3CCN(C)CC3)n2)on1
Storage condition	2-8℃

Synonyms

xl-228

unii-33m2xsk003

2,4-Pyrimidinediamine, N-(5-cyclopropyl-1H-pyrazol-3-yl)-N-[[3-(1-methylethyl)-5-isoxazolyl]methyl]-6-(4-methyl-1-piperazinyl)-

N-(5-Cyclopropyl-1H-pyrazol-3-yl)-N-[(3-isopropyl-1,2-oxazol-5-yl)methyl]-6-(4-methyl-1-piperazinyl)-2,4-pyrimidinediamine

XL228

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