NAV
Explore a selection of essential drug information below, or:
Unlock enhanced features & extensive drug insights. Create a free account.
Explore the full scope of our drug knowledge tailored for pharmaceutical research needs in our data library. Learn more.

Navitoclax

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

Explore a selection of our essential drug information below, or:

CREATE FREE ACCOUNT
Full Drug Profiles
Unlock enhanced features & extensive drug insights, including detailed interaction data & regulatory status. Create a free account.
SUBSCRIBERECOMMENDED FOR PHARMA
Data Packages
Explore the full scope of our drug knowledge tailored for pharmaceutical research needs in our data library. Learn more.

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
Similar Structures
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
Unlock the secrets to drugging the undruggable
Discover how groundbreaking research is turning "undruggable" targets into therapeutic opportunities.
Download eBook
Unlock the secrets to drugging the undruggable
Download eBook

Pharmacology

Indication

Not Available

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
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
ABcl-2-like protein 1
inhibitor
Humans
AG1/S-specific cyclin-D1
inhibitor
Humans
AApoptosis regulator Bcl-2
inhibitor
Humans
ABcl-2-like protein 2
inhibitor
Humans
UBcl2-associated agonist 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
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
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
Integrate drug-drug
interactions in your software
AmbroxolThe risk or severity of methemoglobinemia can be increased when Navitoclax is combined with Ambroxol.
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.
Food Interactions
Not Available

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Navitoclax dihydrochlorideW8FZ00AY2S1093851-28-5WDVGRPCSLPVWKC-VROLVAQFSA-N

Categories

ATC Codes
L01XX78 — Navitoclax
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
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Unlock 175K+ rows when you subscribe.View sample data
3Active Not RecruitingTreatmentMyelofibrosis2somestatusstop reasonjust information to hide
2Active Not RecruitingTreatmentMyelofibrosis1somestatusstop reasonjust information to hide
2Active Not RecruitingTreatmentRefractory Mantle Cell Lymphoma1somestatusstop reasonjust information to hide
2CompletedBasic ScienceChronic Lymphocytic Leukemia1somestatusstop reasonjust information to hide
2CompletedTreatmentChronic Lymphocytic Leukemia1somestatusstop reasonjust information to hide

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/MSsplash10-00di-0040000019-886a9ecb5d9b751f3a90
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0910000024-d982bf539473c89afa44
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-0000100109-66af35397b351a58f651
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-1900000211-bdb59775d9a3ec214adc
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0032-1710000239-c82f72d78e0972c9c4a6
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0kh9-5301310289-8c8a98b3c6372b5ba1cd
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-284.64337
predicted
DeepCCS 1.0 (2019)
[M+H]+286.3671
predicted
DeepCCS 1.0 (2019)
[M+Na]+292.59152
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details1. Bcl-2-like protein 1
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Potent inhibitor of cell death. Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis
Specific Function
Bh domain binding
Gene Name
BCL2L1
Uniprot ID
Q07817
Uniprot Name
Bcl-2-like protein 1
Molecular Weight
26048.8 Da
References
  1. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Details2. G1/S-specific cyclin-D1
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:33854235, PubMed:8114739, PubMed:8302605). Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:8114739, PubMed:8302605). Hypophosphorylates RB1 in early G(1) phase (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:8114739, PubMed:8302605). Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:8302605). Also a substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity (PubMed:15241418). Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex (PubMed:9106657). Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner (PubMed:16569215, PubMed:18417529)
Specific Function
Cyclin-dependent protein serine/threonine kinase activator activity
Gene Name
CCND1
Uniprot ID
P24385
Uniprot Name
G1/S-specific cyclin-D1
Molecular Weight
33728.74 Da
References
  1. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Details3. Apoptosis regulator Bcl-2
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells (PubMed:1508712, PubMed:8183370). Regulates cell death by controlling the mitochondrial membrane permeability (PubMed:11368354). Appears to function in a feedback loop system with caspases (PubMed:11368354). Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1) (PubMed:11368354). Also acts as an inhibitor of autophagy: interacts with BECN1 and AMBRA1 during non-starvation conditions and inhibits their autophagy function (PubMed:18570871, PubMed:20889974, PubMed:21358617). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785)
Specific Function
Bh domain binding
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]
  2. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Details4. Bcl-2-like protein 2
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX
Specific Function
Bh domain binding
Gene Name
BCL2L2
Uniprot ID
Q92843
Uniprot Name
Bcl-2-like protein 2
Molecular Weight
20746.24 Da
References
  1. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Details5. Bcl2-associated agonist of cell death
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General 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 repressor activity of Bcl-X(L), but not that of Bcl-2 (By similarity). Appears to act as a link between growth factor receptor signaling and the apoptotic pathways
Specific Function
Cysteine-type endopeptidase activator activity involved in apoptotic process
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 August 26, 2024 19:23