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Details

Stereochemistry ABSOLUTE
Molecular Formula C25H28N6O2
Molecular Weight 444.5298
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of XL-019

SMILES

C1C[C@@]([H])(C(=O)Nc2ccc(cc2)-c3ccnc(Nc4ccc(cc4)N5CCOCC5)n3)NC1

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 444.5298
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

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

XL-019 is a potent inhibitor of JAK2 (IC50 = 2 nM), and is selective for JAK2 versus the other members of the JAK kinase family (JAK1 IC50 = 130 nM, JAK3 IC50 = 250 nM, TYK2 IC50 = 340 nM). It is active against both wild type and mutationally activated forms of JAK2, and showed good oral bioavailability and pharmacodynamic properties in preclinical studies. Activating mutations in JAK2 are frequently observed in patients with myeloproliferative disorders such as myelofibrosis, polycythemia vera and essential thrombocythemia. JAK2 activity is also upregulated via multiple mechanisms in many lymphomas and solid tumors. XL-019 was being developed by Exelixis for the treatment of myelofibrosis and polycythaemia vera.

Approval Year

T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
21 h
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

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​
PubMed

PubMed

TitleDatePubMed
SAR and in vivo evaluation of 4-aryl-2-aminoalkylpyrimidines as potent and selective Janus kinase 2 (JAK2) inhibitors.
2012 Dec 15
Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application.
2013 Jan 16
Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor.
2014 Mar
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: Due to emerging safety data, however, enrollment of further patients was paused in November 2008, and formally closed in May 2009.
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
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 Sat Jun 26 10:54:05 UTC 2021
Edited
by admin
on Sat Jun 26 10:54:05 UTC 2021
Record UNII
4L1AM42NVA
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
XL-019
Common Name English
2-PYRROLIDINECARBOXAMIDE, N-(4-(2-((4-(4-MORPHOLINYL)PHENYL)AMINO)-4-PYRIMIDINYL)PHENYL)-, (2S)-
Systematic Name English
XL019
Code English
Code System Code Type Description
CAS
945755-56-6
Created by admin on Sat Jun 26 10:54:05 UTC 2021 , Edited by admin on Sat Jun 26 10:54:05 UTC 2021
PRIMARY
DRUG BANK
DB05243
Created by admin on Sat Jun 26 10:54:05 UTC 2021 , Edited by admin on Sat Jun 26 10:54:05 UTC 2021
PRIMARY
ChEMBL
CHEMBL3545328
Created by admin on Sat Jun 26 10:54:05 UTC 2021 , Edited by admin on Sat Jun 26 10:54:05 UTC 2021
PRIMARY
FDA UNII
4L1AM42NVA
Created by admin on Sat Jun 26 10:54:05 UTC 2021 , Edited by admin on Sat Jun 26 10:54:05 UTC 2021
PRIMARY
PUBCHEM
57990869
Created by admin on Sat Jun 26 10:54:05 UTC 2021 , Edited by admin on Sat Jun 26 10:54:05 UTC 2021
PRIMARY
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TARGET -> INHIBITOR
TARGET -> INHIBITOR
TARGET -> INHIBITOR
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ACTIVE MOIETY