Identification

Name
XL765
Accession Number
DB05241
Type
Small Molecule
Groups
Investigational
Description

XL765 is an orally available small molecule that has been shown in preclinical studies to selectively inhibit the activity of phosphoinositide-3 kinase (PI3K) and mammalian target of rapamycin (mTOR). It is being developed by Exelixis, Inc.

Synonyms
Not Available
Categories
UNII
Not Available
CAS number
Not Available
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

For the treatment of various forms of cancer.

Structured Indications
Not Available
Pharmacodynamics

XL765 is an orally available small molecule that has been shown in preclinical studies to selectively inhibit the activity of phosphoinositide-3 kinase (PI3K) and mammalian target of rapamycin (mTOR). Activation of PI3K is a frequent event in human tumors, promoting tumor cell growth, survival, and resistance to chemotherapy and radiotherapy. mTOR is also frequently activated in human tumors and plays a central role in tumor cell growth. mTOR can be activated via upregulation of PI3K, or via PI3K-independent mechanisms. Inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells, whereas inactivation of mTOR has been shown to inhibit the growth of tumor cells. In preclinical studies, XL765 slowed tumor growth or caused tumor shrinkage in multiple preclinical cancer models, including breast, lung, ovarian, and prostate cancers, and gliomas. XL765 has also been shown to enhance the anti-tumor effects of several chemotherapeutic agents in preclinical cancer models. XL765 has at least a 24-hour duration of action against both PI3K and mTOR readouts in tumors in vivo following a single oral (PO) dose of 30-100 mg/kg.

Mechanism of action

XL765 inhibits the activity of phosphoinositide-3 kinase (PI3K), which is frequently activated in tumors and promotes cell growth, survival and resistance to chemotherapy and radiotherapy. XL765 also inhibits mammalian target of rapamycin (mTOR), which also is activated frequently in human tumors and plays a central role in tumor cell growth. XL765 potently inhibits Class I PI3K isoforms and mTOR.

TargetActionsOrganism
UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoformNot AvailableHuman
UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoformNot AvailableHuman
UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoformNot AvailableHuman
UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoformNot AvailableHuman
USerine/threonine-protein kinase mTORNot 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
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Link [Link]
External Links
PubChem Substance
347910044

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAstrocytoma, Grade IV / Glioblastomas1
1CompletedTreatmentCancers1
1CompletedTreatmentCancers / Lung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedTreatmentGlioblastoma Multiforme / Malignant Gliomas / Mixed Gliomas1
1, 2CompletedTreatmentCancer, Breast1

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific Function
Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recr...
Gene Name
PIK3CG
Uniprot ID
P48736
Uniprot Name
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Molecular Weight
126452.625 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Phosphatidylinositol-4,5-bisphosphate 3-kinase activity
Specific Function
Phosphoinositide-3-kinase (PI3K) that phosphorylates PftdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by rec...
Gene Name
PIK3CD
Uniprot ID
O00329
Uniprot Name
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
Molecular Weight
119478.065 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Phosphatidylinositol-4,5-bisphosphate 3-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
PIK3CB
Uniprot ID
P42338
Uniprot Name
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
Molecular Weight
122761.225 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Tfiiic-class transcription factor binding
Specific Function
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. MTOR directly...
Gene Name
MTOR
Uniprot ID
P42345
Uniprot Name
Serine/threonine-protein kinase mTOR
Molecular Weight
288889.05 Da

Drug created on October 21, 2007 16:24 / Updated on November 06, 2017 06:45