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Details

Stereochemistry ACHIRAL
Molecular Formula C22H31N9O
Molecular Weight 437.5412
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of XL-228

SMILES

CC(C)C1=NOC(CNC2=NC(=CC(NC3=NNC(=C3)C4CC4)=N2)N5CCN(C)CC5)=C1

InChI

InChIKey=ALKJNCZNEOTEMP-UHFFFAOYSA-N
InChI=1S/C22H31N9O/c1-14(2)17-10-16(32-29-17)13-23-22-25-19(24-20-11-18(27-28-20)15-4-5-15)12-21(26-22)31-8-6-30(3)7-9-31/h10-12,14-15H,4-9,13H2,1-3H3,(H3,23,24,25,26,27,28)

HIDE SMILES / InChI

Molecular Formula C22H31N9O
Molecular Weight 437.5412
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800026676

XL-228 is a third generation inhibitor of Abl that shows efficacy in a variety of cell lines, including those exhibiting T315I mutations. XL-228, a tyrosine kinase inhibitor, is involved in binding to and inhibiting the activities of multiple tyrosine kinases, such as the insulin-like growth factor 1 receptor (IGF1R), Src tyrosine kinase, and Bcr-Abl tyrosine kinase. Blockade of these kinases may result in the inhibition of tumor angiogenesis, cell proliferation, and metastasis. XL-228 is a multitargeted protein kinase inhibitor targeting IGF1R, the aurora kinases, IGF-1R, cSrc, BCR/Abl and SRC kinases. XL-228 displays anticancer chemotherapeutic activity and it was in clinical trials as a potential treatment for chronic myelogenous leukemia (CML). On 22 Feb 2011 phase I clinical studies for chronic myeloid leukaemia and cancer in USA were discontinued.

Originator

Curator's Comment: # Exelixis

Approval Year

Doses

Doses

DosePopulationAdverse events​
6.5 mg/kg 1 times / week multiple, intravenous
MTD
Dose: 6.5 mg/kg, 1 times / week
Route: intravenous
Route: multiple
Dose: 6.5 mg/kg, 1 times / week
Sources:
unhealthy, 60.1
n = 43
Health Status: unhealthy
Condition: Cancer
Age Group: 60.1
Sex: M+F
Population Size: 43
Sources:

Sample Use Guides

XL-228 is administered as weekly 1-hr IV infusions at the MTD of 6.5 mg/kg. The dose escalation phase is complete, with 41 pts treated with XL-228 at dose levels ranging from 0.45 to 8.0 mg/kg. The dose limiting toxicity was Grade 3 and 4 neutropenia occurring at the 8.0 mg/kg dose level.
Route of Administration: Intravenous
XL-228(5-100 nM) reduced cell survival by 10-70% in a dose and time dependent manner and inhibited migration and invasion of two tumors with high propensity to metastasize, FaDu and H460. Treatment with 50 and 100 nM XL-228 abolished the ability of H460, A549 and FaDu cells to form colony. At 10 nM, XL-228 significantly increased the radiosensitivity of H460, A549 and FaDu cells by enhancement factors (EF, at the survival fraction of 0.5) of 1.52, 1.31 and 1.67 respectively.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:37:56 GMT 2023
Edited
by admin
on Fri Dec 15 15:37:56 GMT 2023
Record UNII
33M2XSK003
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
XL-228
Common Name English
2,4-PYRIMIDINEDIAMINE, N(SUP 4)-(5-CYCLOPROPYL-1H-PYRAZOL-3-YL)-N(SUP 2)-((3-(1-METHYLETHYL)-5-ISOXAZOLYL)METHYL)-6-(4-METHYL-1-PIPERAZINYL)-
Common Name English
EXEL-2280
Common Name English
XL228
Code English
Code System Code Type Description
DRUG BANK
DB05184
Created by admin on Fri Dec 15 15:37:56 GMT 2023 , Edited by admin on Fri Dec 15 15:37:56 GMT 2023
PRIMARY
NCI_THESAURUS
C68929
Created by admin on Fri Dec 15 15:37:56 GMT 2023 , Edited by admin on Fri Dec 15 15:37:56 GMT 2023
PRIMARY
CAS
898280-07-4
Created by admin on Fri Dec 15 15:37:56 GMT 2023 , Edited by admin on Fri Dec 15 15:37:56 GMT 2023
PRIMARY
CAS
952306-27-3
Created by admin on Fri Dec 15 15:37:56 GMT 2023 , Edited by admin on Fri Dec 15 15:37:56 GMT 2023
NO STRUCTURE GIVEN
PUBCHEM
59757974
Created by admin on Fri Dec 15 15:37:56 GMT 2023 , Edited by admin on Fri Dec 15 15:37:56 GMT 2023
PRIMARY
ChEMBL
CHEMBL3545085
Created by admin on Fri Dec 15 15:37:56 GMT 2023 , Edited by admin on Fri Dec 15 15:37:56 GMT 2023
PRIMARY
FDA UNII
33M2XSK003
Created by admin on Fri Dec 15 15:37:56 GMT 2023 , Edited by admin on Fri Dec 15 15:37:56 GMT 2023
PRIMARY
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ACTIVE MOIETY