XL-019

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H28N6O2
Molecular Weight	444.5288
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C(NC1=CC=C(C=C1)C2=NC(NC3=CC=C(C=C3)N4CCOCC4)=NC=C2)[C@@H]5CCCN5

InChI

InChIKey=ISOCDPQFIXDIMS-QHCPKHFHSA-N

InChI=1S/C25H28N6O2/c32-24(23-2-1-12-26-23)28-19-5-3-18(4-6-19)22-11-13-27-25(30-22)29-20-7-9-21(10-8-20)31-14-16-33-17-15-31/h3-11,13,23,26H,1-2,12,14-17H2,(H,28,32)(H,27,29,30)/t23-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C25H28N6O2
Molecular Weight	444.5288
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24374145
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/24252238 | https://www.ncbi.nlm.nih.gov/pubmed/23127890

XL019 is a potent and selective JAK2 inhibitor. XL019 shows 50-fold or greater selectivity for JAK2, versus a panel of over 100 serine/threonine and tyrosine kinases, including other members of the JAK family. XL019 is non-selective for JAK2V617F or wild-type JAK2 and potently inhibits STAT3 and STAT5 phosphorylation in cells harboring either JAK2V617F or wild-type JAK2. Unfortunately, XL019 treatment was associated with the unexpected occurrence of neurotoxicity. Phase I clinical trials have been terminated.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tyrosine-protein kinase JAK2 59 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23127890	Inhibitor 8504		2.2 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Polycythemia vera 18 Sources: https://clinicaltrials.gov/ct2/show/NCT00595829	Primary	Phase I 438	Unknown Approved Use Unknown
Myelofibrosis 15 Sources: https://clinicaltrials.gov/ct2/show/NCT00522574	Primary	Phase I 438	Unknown Approved Use Unknown
Thrombocythemia 4 Sources: https://clinicaltrials.gov/ct2/show/NCT00522574	Primary	Phase I 438	Unknown Approved Use Unknown

T_1/2

Value	Dose	Co-administered	Analyte	Population
21 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24374145/	300 mg 1 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		XL-019 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741

Drug as perpetrator

Target	Modality	Activity
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363680792	inconclusive [IC50 23.9185 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363680792	no
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29187454/ \| https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363680792	yes [IC50 14.581 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363680792	yes [IC50 2.1317 uM]

PubMed

Title	Date	PubMed
Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor.	2014-03	24374145
Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application.	2013-01-16	24252238
SAR and in vivo evaluation of 4-aryl-2-aminoalkylpyrimidines as potent and selective Janus kinase 2 (JAK2) inhibitors.	2012-12-15	23127890

Patents

Sample Use Guides

In Vivo Use Guide

21 patients were treated in 28-day cycles with XL019 in subsequent order: 25 mg continuously daily (n = 8), 25 mg Monday/Wednesday/Friday (25 mg TIW, n = 8), and 50 mg continuously daily (n = 5).

Route of Administration: Oral

In Vitro Use Guide

XL019 activity was evaluated in HEL 92.1.7 cells as STAT1 (IC50=386.4nM) and STAT3 (IC50=695nM) phosphorylation.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:25:06 GMT 2025` Edited by `admin` on `Mon Mar 31 21:25:06 GMT 2025`
Record UNII	4L1AM42NVA
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

XL-019

Common Name

English

XL019

Preferred Name

English

2-PYRROLIDINECARBOXAMIDE, N-(4-(2-((4-(4-MORPHOLINYL)PHENYL)AMINO)-4-PYRIMIDINYL)PHENYL)-, (2S)-

Systematic Name

English

Code System Code Type Description

NCI_THESAURUS

C90573