XL765
Identification
- Generic Name
- XL765
- DrugBank Accession Number
- DB05241
- Background
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.
- Type
- Small Molecule
- Groups
- Investigational
- Synonyms
- Not Available
Pharmacology
- Indication
For the treatment of various forms of cancer.
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- 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.
Target Actions Organism UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Not Available Humans UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Not Available Humans UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Not Available Humans UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Not Available Humans USerine/threonine-protein kinase mTOR Not Available Humans - 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
- Adverse Effects
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- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- Not Available
- CAS number
- Not Available
- InChI Key
- Not Available
- InChI
- Not Available
- IUPAC Name
- Not Available
- SMILES
- Not Available
References
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 1 Completed Treatment Astrocytoma, Grade IV / High Grade Glioma: Glioblastoma (GBM) 1 1 Completed Treatment Cancer 1 1 Completed Treatment Cancer / Non-Small Cell Lung Cancer (NSCLC) 1 1 Completed Treatment Glioblastoma Multiforme (GBM) / Malignant Glioma / Mixed Gliomas 1 1, 2 Completed Treatment Breast Cancer 1
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
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- 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
- Humans
- 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
- Humans
- 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
- Humans
- 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
- Humans
- 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 at October 21, 2007 22:24 / Updated at June 12, 2020 16:52