NAVITOCLAX

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Synonyms
Status
Molecule Category Free-form
UNII XKJ5VVK2WD
EPA CompTox DTXSID2042640

Structure

InChI Key JLYAXFNOILIKPP-KXQOOQHDSA-N
Smiles CC1(C)CCC(c2ccc(Cl)cc2)=C(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(N[C@H](CCN5CCOCC5)CSc5ccccc5)c(S(=O)(=O)C(F)(F)F)c4)cc3)CC2)C1
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

Physicochemical Descriptors

Property Name Value
Molecular Formula C47H55ClF3N5O6S3
Molecular Weight 974.63
AlogP 8.83
Hydrogen Bond Acceptor 11.0
Hydrogen Bond Donor 2.0
Number of Rotational Bond 16.0
Polar Surface Area 128.36
Molecular species ACID
Aromatic Rings 4.0
Heavy Atoms 65.0

Bioactivity

Mechanism of Action Action Reference
Apoptosis regulator Bcl-2 inhibitor INHIBITOR PubMed PubMed
Protein: Apoptosis regulator Bcl-2
Description: Apoptosis regulator Bcl-2
Organism : Homo sapiens
P10415 ENSG00000171791
Protein: Apoptosis regulator Bcl-X
Description: Bcl-2-like protein 1
Organism : Homo sapiens
Q07817 ENSG00000171552
Protein: Apoptosis regulator Bcl-W
Description: Bcl-2-like protein 2
Organism : Homo sapiens
Q92843 ENSG00000129473
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Oxidoreductase
- 800-1330 - - 90
Ion channel Other ion channel Miscellaneous ion channel Bcl-2 family
- 3-60 21-1803 0-48 -
Other cytosolic protein
- 500 - 245 -
Unclassified protein
- 4 - - -
Assay Description Organism Bioactivity Reference
Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay None 1.0 nM
Displacement of fluorescein labeled Bax peptide from Bcl2 by fluorescence polarization assay None 1.0 nM
Cytotoxicity against IL3-dependent mouse FL5.12 cells overexpressing human Bcl2 assessed as cell viability after 24 hrs by MTS assay in absence of serum Mus musculus 5.9 nM
Cytotoxicity against IL3-dependent mouse FL5.12 cells overexpressing human Bcl-XL assessed as cell viability after 24 hrs by MTS assay in absence of serum Mus musculus 4.2 nM
Cytotoxicity against human NCI-H146 cells assessed as cell viability after 48 hrs in presence of 10% human serum Homo sapiens 86.7 nM
Binding affinity to BH3 binding groove of BclXL None 0.5 nM
Binding affinity to Bcl-xL by competitive fluorescence polarization assay None 1.0 nM
Binding affinity to Bcl-xl None 36.0 nM
Cytotoxicity against human NCI-H146 after 48 hrs by MTS assay in presence of 10% human serum Homo sapiens 80.0 nM
Cytotoxicity against human NCI-H889 after 48 hrs by MTS assay in presence of 10% human serum Homo sapiens 120.0 nM
Cytotoxicity against human NCI-H1963 after 48 hrs by MTS assay in presence of 10% human serum Homo sapiens 51.0 nM
Cytotoxicity against human NCI-H1417 cells assessed as growth inhibition after 4 days by WST assay Homo sapiens 54.2 nM
Cytotoxicity against human NCI-H187 cells assessed as growth inhibition after 4 days by WST assay Homo sapiens 38.4 nM
Cytotoxicity against human NCI-H1963 cells assessed as growth inhibition after 4 days by WST assay Homo sapiens 26.6 nM
SANGER: Inhibition of human NCI-H209 cell growth in a cell viability assay. Homo sapiens 87.04 nM
SANGER: Inhibition of human NCI-H720 cell growth in a cell viability assay. Homo sapiens 40.11 nM
SANGER: Inhibition of human NH-12 cell growth in a cell viability assay. Homo sapiens 107.44 nM
SANGER: Inhibition of human NKM-1 cell growth in a cell viability assay. Homo sapiens 16.99 nM
SANGER: Inhibition of human NMC-G1 cell growth in a cell viability assay. Homo sapiens 811.21 nM
SANGER: Inhibition of human NTERA-S-cl-D1 cell growth in a cell viability assay. Homo sapiens 500.19 nM
SANGER: Inhibition of human OAW-28 cell growth in a cell viability assay. Homo sapiens 783.7 nM
SANGER: Inhibition of human OAW-42 cell growth in a cell viability assay. Homo sapiens 961.46 nM
SANGER: Inhibition of human P12-ICHIKAWA cell growth in a cell viability assay. Homo sapiens 77.78 nM
SANGER: Inhibition of human PA-1 cell growth in a cell viability assay. Homo sapiens 956.42 nM
SANGER: Inhibition of human QIMR-WIL cell growth in a cell viability assay. Homo sapiens 42.87 nM
SANGER: Inhibition of human RD cell growth in a cell viability assay. Homo sapiens 758.99 nM
SANGER: Inhibition of human RH-18 cell growth in a cell viability assay. Homo sapiens 60.48 nM
SANGER: Inhibition of human RMG-I cell growth in a cell viability assay. Homo sapiens 494.64 nM
SANGER: Inhibition of human RPMI-8226 cell growth in a cell viability assay. Homo sapiens 456.52 nM
SANGER: Inhibition of human RS4-11 cell growth in a cell viability assay. Homo sapiens 25.87 nM
SANGER: Inhibition of human SK-NEP-1 cell growth in a cell viability assay. Homo sapiens 72.13 nM
SANGER: Inhibition of human SW1417 cell growth in a cell viability assay. Homo sapiens 554.38 nM
SANGER: Inhibition of human 697 cell growth in a cell viability assay. Homo sapiens 108.39 nM
SANGER: Inhibition of human A427 cell growth in a cell viability assay. Homo sapiens 930.22 nM
SANGER: Inhibition of human A704 cell growth in a cell viability assay. Homo sapiens 426.7 nM
SANGER: Inhibition of human ALL-PO cell growth in a cell viability assay. Homo sapiens 219.88 nM
SANGER: Inhibition of human ATN-1 cell growth in a cell viability assay. Homo sapiens 47.33 nM
SANGER: Inhibition of human BE-13 cell growth in a cell viability assay. Homo sapiens 364.59 nM
SANGER: Inhibition of human BEN cell growth in a cell viability assay. Homo sapiens 239.68 nM
SANGER: Inhibition of human BV-173 cell growth in a cell viability assay. Homo sapiens 23.14 nM
SANGER: Inhibition of human TGBC24TKB cell growth in a cell viability assay. Homo sapiens 457.78 nM
SANGER: Inhibition of human TGW cell growth in a cell viability assay. Homo sapiens 46.33 nM
SANGER: Inhibition of human WM-115 cell growth in a cell viability assay. Homo sapiens 277.38 nM
SANGER: Inhibition of human CCRF-CEM cell growth in a cell viability assay. Homo sapiens 335.29 nM
SANGER: Inhibition of human CHP-134 cell growth in a cell viability assay. Homo sapiens 163.06 nM
SANGER: Inhibition of human COR-L88 cell growth in a cell viability assay. Homo sapiens 365.4 nM
SANGER: Inhibition of human D-283MED cell growth in a cell viability assay. Homo sapiens 176.86 nM
SANGER: Inhibition of human DB cell growth in a cell viability assay. Homo sapiens 570.8 nM
SANGER: Inhibition of human DOHH-2 cell growth in a cell viability assay. Homo sapiens 410.23 nM
SANGER: Inhibition of human DU-145 cell growth in a cell viability assay. Homo sapiens 899.23 nM
SANGER: Inhibition of human DU-4475 cell growth in a cell viability assay. Homo sapiens 654.27 nM
SANGER: Inhibition of human ECC10 cell growth in a cell viability assay. Homo sapiens 37.92 nM
SANGER: Inhibition of human EM-2 cell growth in a cell viability assay. Homo sapiens 199.18 nM
SANGER: Inhibition of human EW-13 cell growth in a cell viability assay. Homo sapiens 583.41 nM
SANGER: Inhibition of human EW-16 cell growth in a cell viability assay. Homo sapiens 813.28 nM
SANGER: Inhibition of human EW-18 cell growth in a cell viability assay. Homo sapiens 68.41 nM
SANGER: Inhibition of human EW-22 cell growth in a cell viability assay. Homo sapiens 466.71 nM
SANGER: Inhibition of human EW-3 cell growth in a cell viability assay. Homo sapiens 80.53 nM
SANGER: Inhibition of human EoL-1-cell cell growth in a cell viability assay. Homo sapiens 6.693 nM
SANGER: Inhibition of human HAL-01 cell growth in a cell viability assay. Homo sapiens 725.49 nM
SANGER: Inhibition of human HCC1569 cell growth in a cell viability assay. Homo sapiens 251.06 nM
SANGER: Inhibition of human HCC38 cell growth in a cell viability assay. Homo sapiens 801.9 nM
SANGER: Inhibition of human HL-60 cell growth in a cell viability assay. Homo sapiens 29.08 nM
SANGER: Inhibition of human HPAF-II cell growth in a cell viability assay. Homo sapiens 926.28 nM
SANGER: Inhibition of human HuO9 cell growth in a cell viability assay. Homo sapiens 267.15 nM
SANGER: Inhibition of human IST-SL1 cell growth in a cell viability assay. Homo sapiens 353.43 nM
SANGER: Inhibition of human J-RT3-T3-5 cell growth in a cell viability assay. Homo sapiens 608.08 nM
SANGER: Inhibition of human KARPAS-45 cell growth in a cell viability assay. Homo sapiens 78.15 nM
SANGER: Inhibition of human KE-37 cell growth in a cell viability assay. Homo sapiens 113.7 nM
SANGER: Inhibition of human KG-1 cell growth in a cell viability assay. Homo sapiens 44.86 nM
SANGER: Inhibition of human KNS-81-FD cell growth in a cell viability assay. Homo sapiens 440.17 nM
SANGER: Inhibition of human KP-N-YN cell growth in a cell viability assay. Homo sapiens 235.73 nM
SANGER: Inhibition of human KY821 cell growth in a cell viability assay. Homo sapiens 29.75 nM
SANGER: Inhibition of human LAMA-84 cell growth in a cell viability assay. Homo sapiens 592.07 nM
SANGER: Inhibition of human LU-134-A cell growth in a cell viability assay. Homo sapiens 186.71 nM
SANGER: Inhibition of human LU-135 cell growth in a cell viability assay. Homo sapiens 185.52 nM
SANGER: Inhibition of human LU-139 cell growth in a cell viability assay. Homo sapiens 204.98 nM
SANGER: Inhibition of human MEG-01 cell growth in a cell viability assay. Homo sapiens 583.2 nM
SANGER: Inhibition of human ML-2 cell growth in a cell viability assay. Homo sapiens 19.83 nM
SANGER: Inhibition of human MOLT-13 cell growth in a cell viability assay. Homo sapiens 466.13 nM
SANGER: Inhibition of human MOLT-16 cell growth in a cell viability assay. Homo sapiens 652.64 nM
SANGER: Inhibition of human MOLT-4 cell growth in a cell viability assay. Homo sapiens 151.69 nM
SANGER: Inhibition of human MS-1 cell growth in a cell viability assay. Homo sapiens 469.33 nM
SANGER: Inhibition of human MV-4-11 cell growth in a cell viability assay. Homo sapiens 15.86 nM
SANGER: Inhibition of human NB12 cell growth in a cell viability assay. Homo sapiens 231.15 nM
SANGER: Inhibition of human NB13 cell growth in a cell viability assay. Homo sapiens 82.03 nM
SANGER: Inhibition of human NB17 cell growth in a cell viability assay. Homo sapiens 71.24 nM
SANGER: Inhibition of human NCI-H1048 cell growth in a cell viability assay. Homo sapiens 509.53 nM
SANGER: Inhibition of human NCI-H1092 cell growth in a cell viability assay. Homo sapiens 102.75 nM
SANGER: Inhibition of human NCI-H1304 cell growth in a cell viability assay. Homo sapiens 461.57 nM
Displacement of FITC-Bid from GST-tagged human Bcl-xL expressed in Escherichia coli after 2 hrs by TR-FRET assay Homo sapiens 3.3 nM
Induction of apoptosis in human RS4:11 cells overexpressing BCL-2 assessed as caspase 3/7 activation after 6 hrs by quantitative luminescence assay Homo sapiens 14.0 nM
Inhibition of human BCL-2 overexpressed in mouse FDC-P1 cells assessed as cell viability after 24 hrs by Cell Titer Glo assay Homo sapiens 15.0 nM
Inhibition of human BCL-xL overexpressed in mouse FDC-P1 cells assessed as cell viability after 24 hrs by Cell Titer Glo assay Homo sapiens 60.0 nM
Inhibition of Bcl-xL/Bim (unknown origin) by ELISA Homo sapiens 4.3 nM
Binding affinity to Bcl-2 (unknown origin) by fluorescence polarization assay Homo sapiens 1.0 nM
Binding affinity to Bcl-XL (unknown origin) by fluorescence polarization assay Homo sapiens 1.0 nM
Binding affinity to BCL2 (unknown origin) by fluorescence polarization assay Homo sapiens 1.0 nM
Binding affinity to MCL1 (unknown origin) by fluorescence polarization assay Homo sapiens 500.0 nM
Binding affinity to Bcl-XL (unknown origin) by fluorescence polarization assay Homo sapiens 0.5 nM
Inhibition of Bcl-2 (unknown origin) by fluorescence polarization assay Homo sapiens 1.0 nM
Inhibition of Bcl-xL (unknown origin) by fluorescence polarization assay Homo sapiens 1.0 nM
Inhibition of Mcl-1 (unknown origin) by fluorescence polarization assay Homo sapiens 550.0 nM
Displacement of Bax-derived peptide from Bcl-2 (unknown origin) by fluorescence polarization assay Homo sapiens 10.3 nM
Displacement of Bad-derived peptide from Bcl-XL (unknown origin) by fluorescence polarization assay Homo sapiens 8.2 nM
Inhibition of Bcl2 (unknown origin) Homo sapiens 0.044 nM
Inhibition of Bcl-xL (unknown origin) Homo sapiens 0.055 nM
Antiproliferative activity against human RS4:11 cells in presence of 10% human serum Homo sapiens 112.0 nM
Antiproliferative activity against human MOLT4 cells in presence of 10% human serum Homo sapiens 303.0 nM
Inhibition of Bcl2 (unknown origin) Homo sapiens 0.044 nM
Inhibition of BCL-XL (unknown origin) by fluorescence polarization assay Homo sapiens 48.0 nM
Inhibition of BCL-2 (unknown origin) by fluorescence polarization assay Homo sapiens 0.01 nM
Inhibition of BCL-W (unknown origin) by fluorescence polarization assay Homo sapiens 245.0 nM
Toxicity in mouse xenografted with human haematological tumor at 12.5 mg/kg, po Mus musculus 83.0 nM
Inhibition of Flu-Bax peptide binding to Bcl2 (unknown origin) by time-resolved fluorescence resonance energy transfer assay Homo sapiens 1.0 nM
Inhibition of Flu-Bax peptide binding to Bcl-xL (unknown origin) by time-resolved fluorescence resonance energy transfer assay Homo sapiens 0.5 nM
Inhibition of Flu-Bax peptide binding to MCl-1 (unknown origin) by time-resolved fluorescence resonance energy transfer assay Homo sapiens 1.0 nM
Inhibition of recombinant human N-terminal GST-tagged Bcl-xl (1 to 209 residues) expressed in Escherichia coli using HyLite Fluor 647-labeled BIM peptide as substrate incubated for 120 to 180 mins by TR-FRET assay Homo sapiens 8.0 nM
Inhibition of recombinant human C-terminal 6xHis-tagged Bcl-2 (M1 to F212 residues) expressed in Escherichia coli using HyLite Fluor 647-labeled BIM peptide as substrate incubated for 120 to 180 mins by TR-FRET assay Homo sapiens 2.0 nM
Inhibition of recombinant human N-terminal 6xHis-tagged Bcl-w (M1 to R171) expressed in Escherichia coli using HyLite Fluor 647-labeled Bim peptide as substrate incubated for 120 to 180 mins by TR-FRET assay Homo sapiens 70.0 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 16.33 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.1 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.1 %
Inhibition of BCL2 (unknown origin) by TR-FRET assay Homo sapiens 0.5 nM
Inhibition of N-His6-tagged human AspH (315-755) expressed in Escherichia coli BL21 (DE3) at 20uM using 1 uM hFX-CP as substrate mixture with 3 uM 2OG, 100 uM L-ascorbic acid and 2 uM FAS incubated for 35 mins by MS analysis Homo sapiens 90.1 %
Inhibition of N-His6-tagged human AspH (315-755) expressed in Escherichia coli BL21 (DE3) using 1 uM hFX-CP as substrate mixture with 3 uM 2OG, 100 uM L-ascorbic acid and high 20 uM FAS incubated for 35 mins by MS analysis Homo sapiens 800.0 nM
Binding affinity to human full-length N-terminal His6-tagged Bcl2 (2 to 206 residues) expressed in Escherichia coli S12 extract by isothermal titration calorimetry Homo sapiens 20.6 nM
Binding affinity to human full-length N-terminal His6-tagged Bcl2 R106A/R109A mutant expressed in Escherichia coli S12 extract by isothermal titration calorimetry Homo sapiens 27.8 nM
Binding affinity to human full-length N-terminal His6-tagged prephosphorylated Bcl2 R106A/R109A mutant expressed in Escherichia coli S12 extract by isothermal titration calorimetry Homo sapiens 30.6 nM
Inhibition of F-Bak binding to GST-tagged BCL-XL (unknown origin) measured after 1 hr by TR-FRET assay Homo sapiens 0.1 nM
Inhibition of F-Bak binding to GST-tagged BCL2 (unknown origin) measured after 1 hr by TR-FRET assay Homo sapiens 0.1 nM
Inhibition of F-Bak binding to GST-tagged MCL1 (unknown origin) measured after 1 hr by TR-FRET assay Homo sapiens 224.0 nM
Cytotoxicity against human MOLT-4 cells assessed as reduction in cell viability measured after 48 hrs by celltiter-glo assay Homo sapiens 300.0 nM
Cytotoxicity against human RS4-11 cells assessed as reduction in cell viability measured after 48 hrs by celltiter-glo assay Homo sapiens 110.0 nM
Antiproliferative activity against human MyLa1929 cells assessed as cell viability measured after 72 hrs by MTS assay Homo sapiens 50.0 nM
Cytotoxicity against human platelet assessed as cell viability measured after 72 hrs by MTS assay Homo sapiens 189.0 nM
Cytotoxicity against platelets in human PRP assessed as reduction in cell viability measured after 48 hrs by MTS assay Homo sapiens 325.0 nM
Cytotoxicity against human RS4-11 cells assessed as reduction in cell viability measured after 48 hrs by MTS assay Homo sapiens 42.6 nM
Cytotoxicity against human MOLT-4 cells assessed as reduction in cell viability measured after 48 hrs by MTS assay Homo sapiens 212.3 nM
Displacement of biotin-tagged LWAAQRYGRELRRMSDEFEGSFKGL from human BCL-XL expressed in Escherichia coli measured after 2 hrs by AlphaScreen assay Homo sapiens 2.07 nM
Displacement of biotin-tagged MRPEPATIAQELRRIGDEFNA from C-terminal His-tagged human BCL-2 (1` to 211 residues) expressed in Escherichia coli measured after 2 hrs by AlphaScreen assay Homo sapiens 0.65 nM

Cross References

Resources Reference
ChEBI 131174
ChEMBL CHEMBL443684
DrugBank DB12340
FDA SRS XKJ5VVK2WD
Guide to Pharmacology 8319
PDB 1XJ
PubChem 24978538
SureChEMBL SCHEMBL522847
ZINC ZINC000150338726
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