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Details

Stereochemistry ABSOLUTE
Molecular Formula C29H35NO8
Molecular Weight 525.5912
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of SONOLISIB

SMILES

C=CCN(CC=C)/C(/[H])=C/1\C2=C(C(=O)C3=C([C@@]([H])(C[C@@]4(C)[C@@]3([H])CCC4=O)OC(=O)C)[C@@]2(C)[C@@]([H])(COC)OC1=O)O

InChI

InChIKey=QIUASFSNWYMDFS-NILGECQDSA-N
InChI=1S/C29H35NO8/c1-7-11-30(12-8-2)14-17-23-26(34)25(33)22-18-9-10-20(32)28(18,4)13-19(37-16(3)31)24(22)29(23,5)21(15-36-6)38-27(17)35/h7-8,14,18-19,21,34H,1-2,9-13,15H2,3-6H3/b17-14+/t18-,19+,21+,28-,29-/m0/s1

HIDE SMILES / InChI

Molecular Formula C29H35NO8
Molecular Weight 525.5912
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 1
Optical Activity UNSPECIFIED

Description
Curator's Comment:: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18269228 | https://clinicaltrials.gov/ct2/show/record/NCT01252628 | https://www.ncbi.nlm.nih.gov/pubmed/27118441 | https://clinicaltrials.gov/ct2/show/record/NCT01259869 | https://www.ncbi.nlm.nih.gov/pubmed/25605819

Sonolisib (PX-866) is a small-molecule inhibitor of the alpha, gamma, and delta isoforms of phosphoinositide 3-kinase (PI3K) with potential antineoplastic activity. Sonolisib inhibits the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) and activation of the PI3K/Akt signaling pathway, which may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Inhibition of the PI3K pathway with Sonolisib leads to inhibition of cell growth and decreased activation of downstream targets in GBM, both in vitro and in vivo, using U87–tumor-bearing mice, including Akt, S6, and mTOR. Sonolisib was in phase II clinical trials by Oncothyreon for the treatment of glioblastoma multiforme and castration-resistant prostate cancer (CRPC). It was in phase I/II clinical trials for the treatment of malignant melanoma, non-small cell lung cancer and Head and neck cancer. In clinical trials, Sonolisib was well tolerated, with common side effects being diarrhea, nausea, vomiting, and elevated liver enzymes. However, no recent development has been reported.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
88.0 nM [IC50]
3100.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.76 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1.21 ng/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2.86 ng/mL
10 mg 10 times / 2 weeks multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2.86 ng/mL
12 mg 10 times / 2 weeks multiple, oral
dose: 12 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4.02 ng/mL
8 mg 10 times / 2 weeks multiple, oral
dose: 8 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
0.73 ng/mL
8 mg 1 times / day multiple, oral
dose: 8 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
2.39 ng/mL
8 mg 1 times / day multiple, oral
dose: 8 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.44 ng/mL
16 mg 10 times / 2 weeks multiple, oral
dose: 16 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2.7 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4.88 ng × h/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
5.53 ng × h/mL
10 mg 10 times / 2 weeks multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
6.82 ng × h/mL
12 mg 10 times / 2 weeks multiple, oral
dose: 12 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
8.77 ng × h/mL
8 mg 10 times / 2 weeks multiple, oral
dose: 8 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3.21 ng × h/mL
8 mg 1 times / day multiple, oral
dose: 8 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
6.47 ng × h/mL
8 mg 1 times / day multiple, oral
dose: 8 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
7.91 ng × h/mL
16 mg 10 times / 2 weeks multiple, oral
dose: 16 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.22 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3.88 h
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
17-OH-PX-866 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
PubMed

PubMed

TitleDatePubMed
Molecular pharmacology and antitumor activity of PX-866, a novel inhibitor of phosphoinositide-3-kinase signaling.
2004 Jul
Synthesis and structure-activity relationships of ring-opened 17-hydroxywortmannins: potent phosphoinositide 3-kinase inhibitors with improved properties and anticancer efficacy.
2008 Mar 13
Cellular and in vivo activity of a novel PI3K inhibitor, PX-866, against human glioblastoma.
2010 Jun
Patents

Patents

Sample Use Guides

8mg PO Daily
Route of Administration: Oral
The antiproliferative effect of PX-866 on cells growing in culture was determined using the sulforhodamine B assay. U251, U87, LN229, and LN18 glioblastoma cells (3 x 10^5) were plated per well on 60-mm plates (Costar, Cambridge, Massachusetts) and maintained in 10% fetal bovine serum-containing medium overnight. The next day, the cells were treated with 0.4 and 0.8 mM PX-866. Seventy-two hours later, cells were pelleted, resuspended in 1 mL of 50 mg/mL propidium iodide in phosphate-buffered saline (PBS) containing 20 mg/mL RNase for a further 30 minutes, and then analyzed for DNA content using a FACSCalibur Flow Cytometer and CellQuest software (BD Biosciences, San Jose, California) for any cell-cycle change.
Substance Class Chemical
Created
by admin
on Sat Jun 26 04:59:45 UTC 2021
Edited
by admin
on Sat Jun 26 04:59:45 UTC 2021
Record UNII
987796874T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SONOLISIB
INN   WHO-DD  
INN  
Official Name English
SONOLISIB [INN]
Common Name English
PX-866
Code English
(4E)-4-(((BIS(PROP-2-EN-1-YL)AMINO)METHYLIDENE)-6-HYDROXY-1.ALPHA.-(METHOXYMETHYL)-3,7,17-TRIOXO-2-OXAANDROSTA-5,8-DIEN-11.ALPHA.-YL ACETATE
Common Name English
SONOLISIB [WHO-DD]
Common Name English
CYCLOPENTA(5,6)NAPHTHO(1,2-C)PYRAN-2,7,10(1H)-TRIONE, 5-(ACETYLOXY)-1-((DI-2-PROPEN-1-YLAMINO)METHYLENE)-4,4A,5,6,6A,8,9,9A-OCTAHYDRO-11-HYDROXY-4-(METHOXYMETHYL)-4A,6A-DIMETHYL-, (1E,4S,4AR,5R,6AS,9AR)-
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 04:59:45 UTC 2021 , Edited by admin on Sat Jun 26 04:59:45 UTC 2021
NCI_THESAURUS C2152
Created by admin on Sat Jun 26 04:59:45 UTC 2021 , Edited by admin on Sat Jun 26 04:59:45 UTC 2021
Code System Code Type Description
DRUG BANK
DB12601
Created by admin on Sat Jun 26 04:59:45 UTC 2021 , Edited by admin on Sat Jun 26 04:59:45 UTC 2021
PRIMARY
ChEMBL
CHEMBL411907
Created by admin on Sat Jun 26 04:59:45 UTC 2021 , Edited by admin on Sat Jun 26 04:59:45 UTC 2021
PRIMARY
CAS
502632-66-8
Created by admin on Sat Jun 26 04:59:45 UTC 2021 , Edited by admin on Sat Jun 26 04:59:45 UTC 2021
PRIMARY
EPA CompTox
502632-66-8
Created by admin on Sat Jun 26 04:59:45 UTC 2021 , Edited by admin on Sat Jun 26 04:59:45 UTC 2021
PRIMARY
FDA UNII
987796874T
Created by admin on Sat Jun 26 04:59:45 UTC 2021 , Edited by admin on Sat Jun 26 04:59:45 UTC 2021
PRIMARY
PUBCHEM
9849735
Created by admin on Sat Jun 26 04:59:45 UTC 2021 , Edited by admin on Sat Jun 26 04:59:45 UTC 2021
PRIMARY
INN
9630
Created by admin on Sat Jun 26 04:59:45 UTC 2021 , Edited by admin on Sat Jun 26 04:59:45 UTC 2021
PRIMARY
NCI_THESAURUS
C78848
Created by admin on Sat Jun 26 04:59:45 UTC 2021 , Edited by admin on Sat Jun 26 04:59:45 UTC 2021
PRIMARY