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

Identification

Generic Name
Navitoclax
DrugBank Accession Number
DB12340
Background

Navitoclax has been used in trials studying the treatment and basic science of Solid Tumors, Non-Hodgkin's Lymphoma, EGFR Activating Mutation, Chronic Lymphoid Leukemia, and Hematological Malignancies, among others.

Navitoclax is an orally bioavailable small molecule inhibitor of Bcl-2 family proteins. It is a substance being studied in the treatment of lymphomas and other types of cancer. It blocks some of the enzymes that keep cancer cells from dying.

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 974.613
Monoisotopic: 973.295508909
Chemical Formula
C47H55ClF3N5O6S3
Synonyms
  • (R)-4-(3-Morpholin-4-Yl-1-Phenylsulfanylmethyl-Propylamino)-N-(4-{4-[2-(4-Chlorophenyl)-5,5-Dimethylcyclohex-1-Enylmethyl]-Piperazin-1-Yl}-Benzoyl)-3-Trifluoromethanesulfonylbenzenesulfonamide
  • Navitoclax
External IDs
  • A-855071.0
  • ABT-263

Pharmacology

Indication

Not Available

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

Navitoclax targets the Bcl-2 family of proteins, the major negative regulators of apoptosis. The Bcl-2 proteins, including Bcl-2, Bcl-xL, and Bcl-w, work by binding to two other groups of proteins-the executioners (Bax, Bak) that actually start the destruction pathway, and the sentinel proteins. Cancer cells frequently overexpress the Bcl-2-like proteins, and thus, when they sustain DNA damage-from radiation, for example-they continue growing. Preventing the Bcl-2-like proteins from binding to the executioners might be able to trigger cell death in the tumor.

TargetActionsOrganism
AApoptosis regulator Bcl-2
inhibitor
Humans
UBcl-2-like protein 2Not AvailableHumans
UBcl2 antagonist of cell deathNot AvailableHumans
Absorption

Not 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.
DrugInteraction
ArticaineThe risk or severity of methemoglobinemia can be increased when Navitoclax is combined with Articaine.
BenzocaineThe risk or severity of methemoglobinemia can be increased when Navitoclax is combined with Benzocaine.
Benzyl alcoholThe risk or severity of methemoglobinemia can be increased when Navitoclax is combined with Benzyl alcohol.
BupivacaineThe risk or severity of methemoglobinemia can be increased when Navitoclax is combined with Bupivacaine.
ButacaineThe risk or severity of methemoglobinemia can be increased when Navitoclax is combined with Butacaine.
ButambenThe risk or severity of methemoglobinemia can be increased when Navitoclax is combined with Butamben.
CapsaicinThe risk or severity of methemoglobinemia can be increased when Navitoclax is combined with Capsaicin.
ChloroprocaineThe risk or severity of methemoglobinemia can be increased when Navitoclax is combined with Chloroprocaine.
CinchocaineThe risk or severity of methemoglobinemia can be increased when Navitoclax is combined with Cinchocaine.
CocaineThe risk or severity of methemoglobinemia can be increased when Navitoclax is combined with Cocaine.
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Food Interactions
Not Available

Products

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Product Ingredients
IngredientUNIICASInChI Key
Navitoclax Bis-HydrochlorideNot AvailableNot AvailableNot applicable

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Phenylpiperazines
Alternative Parents
N-arylpiperazines / Aminobenzenesulfonamides / Aminobenzoic acids and derivatives / Benzenesulfonyl compounds / Thiophenol ethers / Aniline and substituted anilines / Phenylalkylamines / Benzoyl derivatives / Dialkylarylamines / Alkylarylthioethers
show 21 more
Substituents
Alkyl fluoride / Alkyl halide / Alkylarylthioether / Amine / Amino acid or derivatives / Aminobenzenesulfonamide / Aminobenzoic acid or derivatives / Aminosulfonyl compound / Aniline or substituted anilines / Aromatic heteromonocyclic compound
show 48 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
XKJ5VVK2WD
CAS number
923564-51-6
InChI Key
JLYAXFNOILIKPP-KXQOOQHDSA-N
InChI
InChI=1S/C47H55ClF3N5O6S3/c1-46(2)20-18-42(34-8-12-37(48)13-9-34)36(31-46)32-55-22-24-56(25-23-55)39-14-10-35(11-15-39)45(57)53-65(60,61)41-16-17-43(44(30-41)64(58,59)47(49,50)51)52-38(19-21-54-26-28-62-29-27-54)33-63-40-6-4-3-5-7-40/h3-17,30,38,52H,18-29,31-33H2,1-2H3,(H,53,57)/t38-/m1/s1
IUPAC Name
4-(4-{[2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-(4-{[(2R)-4-(morpholin-4-yl)-1-(phenylsulfanyl)butan-2-yl]amino}-3-trifluoromethanesulfonylbenzenesulfonyl)benzamide
SMILES
[H][C@@](CCN1CCOCC1)(CSC1=CC=CC=C1)NC1=C(C=C(C=C1)S(=O)(=O)NC(=O)C1=CC=C(C=C1)N1CCN(CC2=C(CCC(C)(C)C2)C2=CC=C(Cl)C=C2)CC1)S(=O)(=O)C(F)(F)F

References

General References
  1. Lock R, Carol H, Houghton PJ, Morton CL, Kolb EA, Gorlick R, Reynolds CP, Maris JM, Keir ST, Wu J, Smith MA: Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008 Jun;50(6):1181-9. [Article]
PubChem Compound
24978538
PubChem Substance
347828599
ChemSpider
21864722
BindingDB
50270877
ChEBI
131174
ChEMBL
CHEMBL443684
ZINC
ZINC000150338726
PDBe Ligand
1XJ
Wikipedia
Navitoclax
PDB Entries
4lvt / 4qnq / 6qgh

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentMyelofibrosis1
3RecruitingTreatmentMyelofibrosis1
2Active Not RecruitingTreatmentMyelofibrosis1
2CompletedBasic ScienceChronic Lymphocytic Leukemia (CLL)1
2CompletedTreatmentChronic Lymphocytic Leukemia (CLL)1
2CompletedTreatmentPlatinum-resistant or Refractory Ovarian Cancer1
2TerminatedTreatmentProstate Cancer1
2WithdrawnTreatmentB-Cell Chronic Lymphocytic Leukemia (B-CLL)1
2WithdrawnTreatmentDiffuse Large B-Cell Lymphoma (DLBCL)1
1Active Not RecruitingTreatmentAdvanced Lung Non-Squamous Non-Small Cell Carcinoma / Metastatic Non-Squamous Non-Small Cell Lung Carcinoma / Stage III Non-Small Cell Lung Cancer AJCC v7 / Stage IIIA Non-Small Cell Lung Cancer AJCC v7 / Stage IIIB Non-Small Cell Lung Cancer AJCC v7 / Stage IV Non-Small Cell Lung Cancer AJCC v71

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 Solubility0.000212 mg/mLALOGPS
logP7.77ALOGPS
logP7.93Chemaxon
logS-6.7ALOGPS
pKa (Strongest Acidic)4.26Chemaxon
pKa (Strongest Basic)8.3Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count10Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area128.36 Å2Chemaxon
Rotatable Bond Count16Chemaxon
Refractivity256.36 m3·mol-1Chemaxon
Polarizability99.45 Å3Chemaxon
Number of Rings7Chemaxon
Bioavailability0Chemaxon
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

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appea...
Gene Name
BCL2
Uniprot ID
P10415
Uniprot Name
Apoptosis regulator Bcl-2
Molecular Weight
26265.66 Da
References
  1. Hoffman-Luca CG, Ziazadeh D, McEachern D, Zhao Y, Sun W, Debussche L, Wang S: Elucidation of Acquired Resistance to Bcl-2 and MDM2 Inhibitors in Acute Leukemia In Vitro and In Vivo. Clin Cancer Res. 2015 Jun 1;21(11):2558-68. doi: 10.1158/1078-0432.CCR-14-2506. Epub 2015 Mar 9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein homodimerization activity
Specific Function
Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX.
Gene Name
BCL2L2
Uniprot ID
Q92843
Uniprot Name
Bcl-2-like protein 2
Molecular Weight
20746.24 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein kinase binding
Specific Function
Promotes cell death. Successfully competes for the binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of heterodimerization of these proteins with BAX. Can reverse the death represso...
Gene Name
BAD
Uniprot ID
Q92934
Uniprot Name
Bcl2-associated agonist of cell death
Molecular Weight
18391.765 Da

Drug created at October 20, 2016 22:00 / Updated at December 01, 2022 11:27