Pilaralisib

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Pilaralisib
Accession Number
DB11772  (DB05240)
Type
Small Molecule
Groups
Investigational
Description

Pilaralisib is an orally available small molecule that selectively inhibits the activity of phosphoinositide-3 kinase (PI3K). Pilaralisib has been used in trials studying the treatment of Cancer, Lymphoma, Solid Tumors, Glioblastoma, and Breast Cancer, among others.

Structure
Thumb
Synonyms
Not Available
External IDs
SAR-245408 / SAR245408 / XL-147 / XL147
Categories
UNII
60ES45KTMK
CAS number
934526-89-3
Weight
Average: 541.02
Monoisotopic: 540.1346522
Chemical Formula
C25H25ClN6O4S
InChI Key
QINPEPAQOBZPOF-UHFFFAOYSA-N
InChI
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)
IUPAC Name
2-amino-N-[3-({3-[(2-chloro-5-methoxyphenyl)amino]quinoxalin-2-yl}sulfamoyl)phenyl]-2-methylpropanamide
SMILES
COC1=CC=C(Cl)C(NC2=C(NS(=O)(=O)C3=CC(NC(=O)C(C)(C)N)=CC=C3)N=C3C=CC=CC3=N2)=C1

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics

In preclinical studies, Pilaralisib slowed tumor growth or caused tumor shrinkage in multiple preclinical cancer models, including breast, lung, ovarian, and prostate cancers, and gliomas. Pilaralisib has also been shown to enhance the anti- tumor effects of several chemotherapeutic agents and an inhibitor of epidermal growth factor receptor (EGFR) in preclinical cancer models.

Mechanism of action

Pilaralisib is an orally available small molecule that selectively inhibits the activity of phosphoinositide-3 kinase (PI3K). Activation of PI3K is a frequent event in human tumors, promoting tumor cell growth, survival, and resistance to chemotherapy and radiotherapy. Inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells.

TargetActionsOrganism
UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoformNot AvailableHuman
Absorption

Orally available

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
56599306
PubChem Substance
347828124
ChemSpider
29340997
ChEMBL
CHEMBL3360203

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableTumors, Solid1
1CompletedTreatmentAstrocytoma, Grade IV / Glioblastomas1
1CompletedTreatmentCancers / Endometrial Carcinoma / Lung Cancer Non-Small Cell Cancer (NSCLC) / Ovarian Carcinoma1
1CompletedTreatmentCancers / Lung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedTreatmentCancers / Malignant Lymphomas1
1CompletedTreatmentNeoplasms Malignant2
1CompletedTreatmentSolid Tumor Cancers1
1WithdrawnTreatmentCancer, Breast / Cancers / Lung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2Active Not RecruitingTreatmentNeoplasms Malignant1
1, 2CompletedTreatmentCancer, Breast1
1, 2CompletedTreatmentCancer, Breast / Neoplasms, Breast1
2CompletedTreatmentEndometrial Cancers / Neoplasms, Endometrial1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0048 mg/mLALOGPS
logP3.98ALOGPS
logP3.27ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)5.99ChemAxon
pKa (Strongest Basic)8.48ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area148.33 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity142.09 m3·mol-1ChemAxon
Polarizability52.89 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acid amides
Alternative Parents
Benzenesulfonamides / Quinoxalines / Benzenesulfonyl compounds / Anilides / Methoxyanilines / Phenoxy compounds / Anisoles / Methoxybenzenes / N-arylamides / Alkyl aryl ethers
show 14 more
Substituents
Alpha-amino acid amide / Quinoxaline / Benzenesulfonamide / Anilide / Benzenesulfonyl group / Methoxyaniline / Phenoxy compound / Phenol ether / N-arylamide / Aniline or substituted anilines
show 37 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific Function
Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate...
Gene Name
PIK3CA
Uniprot ID
P42336
Uniprot Name
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Molecular Weight
124283.025 Da

Drug created on October 20, 2016 14:46 / Updated on December 01, 2017 16:23