Navitoclax

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

Identification

Name
Navitoclax
Accession Number
DB12340  (DB05764)
Type
Small Molecule
Groups
Investigational
Description

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.

Structure
Thumb
Synonyms
Not Available
External IDs
A-855071.0 / ABT-263
Product Ingredients
Not Available
Approved Prescription Products
Not Available
Approved Generic Prescription Products
Not Available
Approved Over the Counter Products
Not Available
Unapproved/Other Products
Not Available
International/Other Brands
Not Available
Brand mixtures
Not Available
Categories
UNII
XKJ5VVK2WD
CAS number
923564-51-6
Weight
Average: 974.613
Monoisotopic: 973.295508909
Chemical Formula
C47H55ClF3N5O6S3
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][[email protected]@](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

Pharmacology

Indication
Not Available
Structured Indications
Not Available
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
UApoptosis regulator Bcl-2Not AvailableHuman
UBcl-2-like protein 2Not AvailableHuman
UBcl2 antagonist of cell deathNot AvailableHuman
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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Navitoclax.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Navitoclax.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Navitoclax.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Navitoclax.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Navitoclax.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Navitoclax.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Navitoclax.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Navitoclax.Approved, Investigational
OleandrinAnvirzel may decrease the cardiotoxic activities of Navitoclax.Experimental
OuabainOuabain may decrease the cardiotoxic activities of Navitoclax.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Navitoclax.Approved, Vet Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Navitoclax.Approved, Investigational
Food Interactions
Not Available

References

Synthesis Reference
Not Available
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. [PubMed:18085673 ]
External Links
ChemSpider
21864722
BindingDB
50270877
ChEBI
94128
ChEMBL
CHEMBL443684
HET
1XJ
ATC Codes
Not Available
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentCD20-Positive Lymphoid Malignancies / Chronic Lymphocytic Leukaemia (CLL) / Haematological Malignancies / Non-Hodgkin's Lymphoma (NHL)1
1CompletedNot AvailableHealthy Female Subjects1
1CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)1
1CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias / Malignant Lymphomas1
1CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Malignant Lymphomas / Tumors, Solid1
1CompletedTreatmentLymphoid Malignancies / Tumors, Solid1
1CompletedTreatmentLymphoma, Including Chronic Lymphocytic Leukemia / Tumors, Solid1
1CompletedTreatmentTumors, Solid5
1Not Yet RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1RecruitingTreatmentChild-Pugh Class A / Child-Pugh Class B / Hepatitis B Infection / Hepatitis C Infection / Liver Cirrhosis / Metastatic Malignant Solid Neoplasm / Recurrent Hepatocellular Carcinoma / Recurrent Malignant Solid Neoplasm / Refractory Malignant Neoplasm / Solid Neoplasms / Stage IV Hepatocellular Carcinoma / Stage IV Hepatocellular Carcinoma AJCC v7 / Unresectable Solid Neoplasm1
1RecruitingTreatmentEGFR Activating Mutation / Recurrent Non-Small Cell Lung Carcinoma / Stage III Non-Small Cell Lung Cancer / Stage III Non-Small Cell Lung Cancer AJCC v7 / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIA Non-Small Cell Lung Cancer AJCC v7 / Stage IIIB Non-Small Cell Lung Cancer / Stage IIIB Non-Small Cell Lung Cancer AJCC v7 / Stage IV Non-Small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer AJCC v71
1, 2CompletedTreatmentLung Cancer Small Cell Lung Cancer (SCLC) / Small Cell Lung Carcinoma1
1, 2RecruitingTreatmentAdvanced Malignant Solid Neoplasm / Extensive Stage Small Cell Lung Carcinoma / KRAS Gene Mutation / Metastatic Malignant Solid Neoplasm / Metastatic Solid Neoplasm / Neoplasms, Advanced Solid / NRAS Gene Mutation / Recurrent Colorectal Carcinoma / Recurrent Lung Carcinoma / Recurrent Non-Small Cell Lung Carcinoma / Recurrent Pancreatic Carcinoma / Recurrent Small Cell Lung Carcinoma / Solid Neoplasms / Stage III Colorectal Cancer / Stage III Colorectal Cancer AJCC v7 / Stage III Lung Cancer / Stage III Lung Cancer AJCC v7 / Stage III Pancreatic Cancer / Stage III Pancreatic Cancer AJCC v6 and v7 / Stage IIIA Colorectal Cancer / Stage IIIA Colorectal Cancer AJCC v7 / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIB Colorectal Cancer / Stage IIIB Colorectal Cancer AJCC v7 / Stage IIIB Non-Small Cell Lung Cancer / Stage IIIC Colorectal Cancer / Stage IIIC Colorectal Cancer AJCC v7 / Stage IV Colorectal Cancer / Stage IV Colorectal Cancer AJCC v7 / Stage IV Lung Cancer / Stage IV Lung Cancer AJCC v7 / Stage IV Non-Small Cell Lung Cancer / Stage IV Pancreatic Cancer / Stage IV Pancreatic Cancer AJCC v6 and v7 / Stage IVA Colorectal Cancer / Stage IVA Colorectal Cancer AJCC v7 / Stage IVB Colorectal Cancer / Stage IVB Colorectal Cancer AJCC v7 / Unresectable Malignant Neoplasm1
1, 2RecruitingTreatmentMetastatic Melanoma / Recurrent Melanoma / Solid Neoplasms / Stage IIIA Cutaneous Melanoma AJCC v7 / Stage IIIA Skin Melanoma / Stage IIIB Cutaneous Melanoma AJCC v7 / Stage IIIB Skin Melanoma / Stage IIIC Cutaneous Melanoma AJCC v7 / Stage IIIC Skin Melanoma / Stage IV Cutaneous Melanoma AJCC v6 and v7 / Stage IV Skin Melanoma1
2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
2Active Not RecruitingTreatmentPlatinum-resistant or Refractory Ovarian Cancer1
2CompletedBasic ScienceChronic Lymphocytic Leukaemia (CLL)1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Follicular Lymphoma (FL) / Lymphoid Malignancies / Mantle Cell Lymphoma (MCL) / Non-Hodgkin's Lymphoma (NHL) / Peripheral T-Cell Lymphoma (PTCL)1
2CompletedTreatmentProstate Cancer1
2Not Yet RecruitingTreatmentMyelofibrosis (MF)1
2WithdrawnTreatmentB-Cell Chronic Lymphocytic Leukemia1
2WithdrawnTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1

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
logP8.06ChemAxon
logS-6.7ALOGPS
pKa (Strongest Acidic)4.23ChemAxon
pKa (Strongest Basic)8.29ChemAxon
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 LC-MS/MS Spectrum - 10V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 10V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, NegativePredicted LC-MS/MSNot Available

Taxonomy

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
Phenylpiperazine / N-arylpiperazine / Aminobenzenesulfonamide / Aminobenzoic acid or derivatives / Benzenesulfonamide / Benzoic acid or derivatives / Benzenesulfonyl group / Aryl thioether / Benzoyl / Tertiary aliphatic/aromatic amine
show 48 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Kind
Protein
Organism
Human
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
Human
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 on October 20, 2016 16:00 / Updated on September 01, 2017 12:19