U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C25H25ClN6O4S
Molecular Weight 541.0238
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PILARALISIB

SMILES

CC(C)(C(=Nc1cccc(c1)S(=O)(=O)N=c2c(=Nc3cc(ccc3Cl)OC)[nH]c4ccccc4[nH]2)O)N

InChI

InChIKey=QINPEPAQOBZPOF-UHFFFAOYSA-N
InChI=1S/C25H25ClN6O4S/c1-25(2,27)24(33)28-15-7-6-8-17(13-15)37(34,35)32-23-22(29-19-9-4-5-10-20(19)30-23)31-21-14-16(36-3)11-12-18(21)26/h4-14H,27H2,1-3H3,(H,28,33)(H,29,31)(H,30,32)

HIDE SMILES / InChI

Molecular Formula C25H25ClN6O4S
Molecular Weight 541.0238
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 https://www.ncbi.nlm.nih.gov/pubmed/25637314

Pilaralisib (XL147, SAR245408) is a potent and highly selective inhibitor of class I phosphatidylinositol 3-kinase (PI3K) (α, β, γ, and δ). In cellular assays, XL147 inhibits the formation of PIP3 in the membrane, and inhibits phosphorylation of AKT, p70S6K, and S6 in multiple tumor cell lines with diverse genetic alterations affecting the PI3K pathway. In a panel of tumor cell lines, XL147 inhibits proliferation with a wide range of potencies, with evidence of an impact of genotype on sensitivity. Repeat-dose administration of XL147 results in significant tumor growth inhibition in multiple human xenograft models in nude mice. Pilaralisib, was being developed by Exelixis and its licensee, Sanofi (formerly sanofi-aventis), for the treatment of solid tumours. However, the product was not listed on Sanofi's early stage pipeline as of end of July 2015 and there have been no recent reports on development identified.

CNS Activity

Curator's Comment:: Brain penetration of pilaralisib (XL147, SAR245408) is not known, however it was effective in glioma xenograft model. In addition effect pilaralisib (XL147, SAR245408) on tumor tissue was studied in subjects with recurrent glioblastoma who are candidates for surgical resection (NCT01240460).

Originator

Curator's Comment:: # Exelixis

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
39.0 nM [IC50]
36.0 nM [IC50]
23.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
600 mg 1 times / day multiple, oral (unknown)
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 25
Health Status: unhealthy
Condition: Refractory Lymphoma, chronic lymphocytic leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources:
DLT: rash...
Disc. AE: Maculopapular rash, diarrhea...
Dose limiting toxicities:
rash (grade 3, 4%)
AEs leading to
discontinuation/dose reduction:
Maculopapular rash (grade 3, 1 pt)
diarrhea (grade 1-3, 1 pt)
pruritus (grade 3, 1 pt)
Lipase increased (grade 2, 1 pt)
diarrhea (grade 3, 1 pt)
increases in transaminase level (grade 2, 1 pt)
ALT increased (grade 1, 1 pt)
neutropenia (grade 3, 1 pt)
pyrexia (grade 2, 1 pt)
pruritic rash (grade 3, 1 pt)
macular rash (grade 3, 1 pt)
vomiting (grade 2, 1 pt)
Nausea (grade 2, 1 pt)
Sources:
600 mg 1 times / day multiple, oral (unknown)
Studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 12
Health Status: unhealthy
Condition: lymphoma
Food Status: UNKNOWN
Population Size: 12
Sources:
DLT: rash generalized, Lipase increased...
Dose limiting toxicities:
rash generalized (grade 3, 1 pt)
Lipase increased (grade 4, 1 pt)
rash maculopapular (grade 3, 1 pt)
Sources:
AEs

AEs

AESignificanceDosePopulation
ALT increased grade 1, 1 pt
Disc. AE
600 mg 1 times / day multiple, oral (unknown)
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 25
Health Status: unhealthy
Condition: Refractory Lymphoma, chronic lymphocytic leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources:
diarrhea grade 1-3, 1 pt
Disc. AE
600 mg 1 times / day multiple, oral (unknown)
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 25
Health Status: unhealthy
Condition: Refractory Lymphoma, chronic lymphocytic leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources:
Lipase increased grade 2, 1 pt
Disc. AE
600 mg 1 times / day multiple, oral (unknown)
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 25
Health Status: unhealthy
Condition: Refractory Lymphoma, chronic lymphocytic leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources:
Nausea grade 2, 1 pt
Disc. AE
600 mg 1 times / day multiple, oral (unknown)
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 25
Health Status: unhealthy
Condition: Refractory Lymphoma, chronic lymphocytic leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources:
increases in transaminase level grade 2, 1 pt
Disc. AE
600 mg 1 times / day multiple, oral (unknown)
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 25
Health Status: unhealthy
Condition: Refractory Lymphoma, chronic lymphocytic leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources:
pyrexia grade 2, 1 pt
Disc. AE
600 mg 1 times / day multiple, oral (unknown)
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 25
Health Status: unhealthy
Condition: Refractory Lymphoma, chronic lymphocytic leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources:
vomiting grade 2, 1 pt
Disc. AE
600 mg 1 times / day multiple, oral (unknown)
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 25
Health Status: unhealthy
Condition: Refractory Lymphoma, chronic lymphocytic leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources:
Maculopapular rash grade 3, 1 pt
Disc. AE
600 mg 1 times / day multiple, oral (unknown)
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 25
Health Status: unhealthy
Condition: Refractory Lymphoma, chronic lymphocytic leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources:
diarrhea grade 3, 1 pt
Disc. AE
600 mg 1 times / day multiple, oral (unknown)
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 25
Health Status: unhealthy
Condition: Refractory Lymphoma, chronic lymphocytic leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources:
macular rash grade 3, 1 pt
Disc. AE
600 mg 1 times / day multiple, oral (unknown)
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 25
Health Status: unhealthy
Condition: Refractory Lymphoma, chronic lymphocytic leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources:
neutropenia grade 3, 1 pt
Disc. AE
600 mg 1 times / day multiple, oral (unknown)
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 25
Health Status: unhealthy
Condition: Refractory Lymphoma, chronic lymphocytic leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources:
pruritic rash grade 3, 1 pt
Disc. AE
600 mg 1 times / day multiple, oral (unknown)
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 25
Health Status: unhealthy
Condition: Refractory Lymphoma, chronic lymphocytic leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources:
pruritus grade 3, 1 pt
Disc. AE
600 mg 1 times / day multiple, oral (unknown)
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 25
Health Status: unhealthy
Condition: Refractory Lymphoma, chronic lymphocytic leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources:
rash grade 3, 4%
DLT
600 mg 1 times / day multiple, oral (unknown)
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 25
Health Status: unhealthy
Condition: Refractory Lymphoma, chronic lymphocytic leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 25
Sources:
rash generalized grade 3, 1 pt
DLT
600 mg 1 times / day multiple, oral (unknown)
Studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 12
Health Status: unhealthy
Condition: lymphoma
Food Status: UNKNOWN
Population Size: 12
Sources:
rash maculopapular grade 3, 1 pt
DLT, Disc. AE
600 mg 1 times / day multiple, oral (unknown)
Studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 12
Health Status: unhealthy
Condition: lymphoma
Food Status: UNKNOWN
Population Size: 12
Sources:
Lipase increased grade 4, 1 pt
DLT, Disc. AE
600 mg 1 times / day multiple, oral (unknown)
Studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy
n = 12
Health Status: unhealthy
Condition: lymphoma
Food Status: UNKNOWN
Population Size: 12
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Patents

Patents

Sample Use Guides

Interim data from a phase I study showed that eight of 23 evaluable patients with non-small cell lung cancer, basal cell carcinoma, chondrosarcoma, or prostate cancer receiving pilaralisib treatment achieved a stable disease for >3 months and six of whom subsequently progressed. In this trial, patients were treated with one of seven dose levels of Pilaralisib (XL147, SAR245408), ranging from 30mg to 900mg daily, on 28-day cycles with a 21 days on and seven days off schedule
Route of Administration: Oral
Pilaralisib (XL147, SAR245408) inhibits B16 melanoma cell migration (370-3333 nM), PC-3 cell migration (13-3333 nM), and VEGF-induced HMVEC tubule formation (370-1000 nM)
Substance Class Chemical
Created
by admin
on Sat Jun 26 05:00:09 UTC 2021
Edited
by admin
on Sat Jun 26 05:00:09 UTC 2021
Record UNII
60ES45KTMK
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PILARALISIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
PILARALISIB [INN]
Common Name English
SAR245408
Code English
SAR-245408
Code English
XL147
Code English
PILARALISIB [WHO-DD]
Common Name English
2-AMINO-N-(3-(N-(3-((2-CHLORO-5-METHOXYPHENYL)AMINO)QUINOXALIN-2-YL)SULFAMOYL)PHENYL)-2-METHYLPROPANAMIDE
Systematic Name English
PILARALISIB [USAN]
Common Name English
2-AMINO-N-(3-((3-(2-CHLORO-5-METHOXYANILINO)QUINOXALIN-2-YL)SULFAMOYL(PHENYL)-2-METHYLPROPANAMIDE
Common Name English
XL-147
Code English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 05:00:09 UTC 2021 , Edited by admin on Sat Jun 26 05:00:09 UTC 2021
NCI_THESAURUS C2152
Created by admin on Sat Jun 26 05:00:09 UTC 2021 , Edited by admin on Sat Jun 26 05:00:09 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL3360203
Created by admin on Sat Jun 26 05:00:09 UTC 2021 , Edited by admin on Sat Jun 26 05:00:09 UTC 2021
PRIMARY
DRUG BANK
DB11772
Created by admin on Sat Jun 26 05:00:09 UTC 2021 , Edited by admin on Sat Jun 26 05:00:09 UTC 2021
PRIMARY
EVMPD
SUB32908
Created by admin on Sat Jun 26 05:00:09 UTC 2021 , Edited by admin on Sat Jun 26 05:00:09 UTC 2021
PRIMARY
CAS
934526-89-3
Created by admin on Sat Jun 26 05:00:09 UTC 2021 , Edited by admin on Sat Jun 26 05:00:09 UTC 2021
PRIMARY
FDA UNII
60ES45KTMK
Created by admin on Sat Jun 26 05:00:09 UTC 2021 , Edited by admin on Sat Jun 26 05:00:09 UTC 2021
PRIMARY
NCI_THESAURUS
C71705
Created by admin on Sat Jun 26 05:00:09 UTC 2021 , Edited by admin on Sat Jun 26 05:00:09 UTC 2021
PRIMARY
PUBCHEM
56599306
Created by admin on Sat Jun 26 05:00:09 UTC 2021 , Edited by admin on Sat Jun 26 05:00:09 UTC 2021
PRIMARY
INN
9708
Created by admin on Sat Jun 26 05:00:09 UTC 2021 , Edited by admin on Sat Jun 26 05:00:09 UTC 2021
PRIMARY
CAS
1033110-57-4
Created by admin on Sat Jun 26 05:00:09 UTC 2021 , Edited by admin on Sat Jun 26 05:00:09 UTC 2021
SUPERSEDED
Related Record Type Details
ACTIVE MOIETY