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

Identification
NamePilaralisib
Accession NumberDB11772  (DB05240)
TypeSmall Molecule
GroupsInvestigational
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
SynonymsNot Available
External IDs SAR-245408 / SAR245408 / XL-147 / XL147
Product Ingredients Not Available
ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII60ES45KTMK
CAS number934526-89-3
WeightAverage: 541.02
Monoisotopic: 540.1346522
Chemical FormulaC25H25ClN6O4S
InChI KeyQINPEPAQOBZPOF-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
IndicationNot 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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoformProteinunknownNot AvailableHumanP42336 details
Related Articles
Absorption

Orally available

Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableTumors, Solid1
1CompletedTreatmentAstrocytoma, Grade IV / Glioblastomas1
1CompletedTreatmentCancers / Endometrial Carcinoma / Non-Small-Cell Lung Carcinoma (NSCLC) / Ovarian Carcinoma1
1CompletedTreatmentCancers / Malignant Lymphomas1
1CompletedTreatmentCancers / Non-Small-Cell Lung Carcinoma (NSCLC)1
1CompletedTreatmentNeoplasms Malignant2
1CompletedTreatmentSolid Tumor Cancers1
1WithdrawnTreatmentCancer, Breast / Cancers / Non-Small-Cell Lung Cancer (NSCLC)1
1, 2Active Not RecruitingTreatmentNeoplasms Malignant1
1, 2CompletedTreatmentCancer, Breast1
1, 2CompletedTreatmentCancer, Breast / Neoplasms, Breast1
2CompletedTreatmentEndometrial Cancers / Neoplasms, Endometrial1
Properties
StateNot Available
Experimental PropertiesNot 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 featuresNot Available
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acid amides
Alternative ParentsBenzenesulfonamides / Quinoxalines / Benzenesulfonyl compounds / Anilides / Methoxyanilines / Phenoxy compounds / Anisoles / Methoxybenzenes / N-arylamides / Alkyl aryl ethers
SubstituentsAlpha-amino acid amide / Quinoxaline / Benzenesulfonamide / Anilide / Benzenesulfonyl group / Methoxyaniline / Phenoxy compound / Phenol ether / N-arylamide / Aniline or substituted anilines
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot 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 phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in...
Gene Name:
PIK3CA
Uniprot ID:
P42336
Molecular Weight:
124283.025 Da
Drug created on October 20, 2016 14:46 / Updated on June 24, 2017 13:35