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Compound Detail

CHEMBL443684

NAVITOCLAX
🧪 Phase III
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🧪 Phase III
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

Basic Information

ChEMBL ID CHEMBL443684
Name NAVITOCLAX
Phase Phase III
Structure Type MOL
InChI Key JLYAXFNOILIKPP-KXQOOQHDSA-N

Known Names

A-855071.0 ABT-263 Navitoclax
488
Targets
653
Activities
4
Assay Types
16
PK Parameters
20
Publications
3
Known Names
16
Indications
3
Mechanisms

Molecular Properties

974.6
MW (Da)
8.83
ALogP
11
HBA
2
HBD
128.4
PSA (Ų)
0.10
QED
3
Ro5 Violations
16
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer
USAN Stem -toclax
USAN Year 2009

Extended Properties

Molecular Formula C47H55ClF3N5O6S3
MW 974.63
Aromatic Rings 4
Heavy Atoms 65
NP-Likeness -1.00

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Apoptosis regulator Bcl-2 inhibitor INHIBITOR Apoptosis regulator Bcl-2
Apoptosis regulator Bcl-X inhibitor INHIBITOR Bcl-2-like protein 1
Apoptosis regulator Bcl-W inhibitor INHIBITOR Bcl-2-like protein 2

Indications

Neoplasms Neoplasms Primary Myelofibrosis Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Mantle-Cell Ovarian Neoplasms Prostatic Neoplasms, Castration-Resistant Hematologic Neoplasms Leukemia Leukemia, Lymphoid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Precursor Cell Lymphoblastic Leukemia-Lymphoma Precursor Cell Lymphoblastic Leukemia-Lymphoma Small Cell Lung Carcinoma

ATC Classification

L01XX78
navitoclax
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 585 meas. best 8.7
EC50 46 meas. best 8.38
Kd 12 meas. best 9.19
Ki 10 meas. best 10.36

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Apoptosis regulator Bcl-2
CHEMBL4860
Ki 10.36 10.36 0.0 3
Bcl-2-like protein 1
CHEMBL4625
Ki 10.26 8.82 0.1 4
Apoptosis regulator Bcl-2
CHEMBL4860
Kd 9.19 7.4 0.7 6
Apoptosis regulator Bcl-2
CHEMBL4860
IC50 8.7 8.2267 2.0 3
Bcl-2-like protein 1
CHEMBL4625
Kd 8.68 7.7333 2.1 3
Bcl-2-like protein 1
CHEMBL4625
IC50 8.48 7.93 3.3 3
NON-PROTEIN TARGET
CHEMBL3879801
EC50 8.38 7.6925 4.2 4
Bcl-xL/Bcl-2-like protein 11
CHEMBL3883287
IC50 8.37 8.37 4.3 1
EOL1
CHEMBL614489
IC50 8.17 8.17 6.7 1
Unchecked
CHEMBL612545
IC50 8.09 7.695 8.2 2
GDM-1
CHEMBL2366157
EC50 7.96 7.96 11.0 1
OCI-AML2
CHEMBL2366220
EC50 7.96 7.96 11.0 1
SIG-M5
CHEMBL2366251
EC50 7.96 7.96 11.0 1
EOL1
CHEMBL614489
EC50 7.96 7.96 11.0 1
RS4-11
CHEMBL2366159
EC50 7.85 7.2533 14.0 3
MV4-11
CHEMBL613835
IC50 7.8 7.8 15.9 1
NKM-1
CHEMBL2366133
IC50 7.77 7.77 17.0 1
ML-2
CHEMBL614356
IC50 7.7 7.7 19.8 1
Bcl-2-like protein 2
CHEMBL4677
Ki 7.68 7.145 21.0 2
BV-173
CHEMBL2366145
IC50 7.64 7.64 23.1 1
RS4-11
CHEMBL2366159
IC50 7.59 7.48 25.9 2
NCI-H1963
CHEMBL2366075
IC50 7.58 7.58 26.6 1
Unchecked
CHEMBL612545
Kd 7.56 7.535 27.8 2
HL-60
CHEMBL383
IC50 7.54 7.54 29.1 1
KY821
CHEMBL2366190
IC50 7.53 7.53 29.8 1
MOLM-13
CHEMBL3706572
EC50 7.52 7.52 30.0 1
Unchecked
CHEMBL612545
EC50 7.52 6.9286 30.0 7
Kasumi 1
CHEMBL613988
EC50 7.52 7.52 30.0 1
NCI-H187
CHEMBL2366276
EC50 7.43 7.43 37.0 1
ECC10
CHEMBL2366117
IC50 7.42 7.42 37.9 1
NCI-H187
CHEMBL2366276
IC50 7.42 7.42 38.4 1
NCI-H720
CHEMBL2366105
IC50 7.4 7.4 40.1 1
HL-60
CHEMBL383
EC50 7.4 7.4 40.0 1
MV4-11
CHEMBL613835
EC50 7.4 7.4 40.0 1
QIMR-WIL
CHEMBL2366337
IC50 7.37 7.37 42.9 1
KG-1
CHEMBL612264
IC50 7.35 7.35 44.9 1
TGW
CHEMBL1075600
IC50 7.33 7.33 46.3 1
ATN-1
CHEMBL2366277
IC50 7.33 7.33 47.3 1
ML-2
CHEMBL614356
EC50 7.3 7.3 50.0 1
NCI-H1963
CHEMBL2366075
EC50 7.29 7.29 51.0 1
NCI-H889
CHEMBL2366169
EC50 7.28 7.1 53.0 2
NCI-H1417
CHEMBL2366149
IC50 7.27 7.27 54.2 1
Bcl2-associated agonist of cell death
CHEMBL3817
Kd 7.26 7.26 55.0 1
RH-18
CHEMBL2366350
IC50 7.22 7.22 60.5 1
SET-2
CHEMBL4523566
EC50 7.22 7.22 60.0 1
EW-18
CHEMBL2366097
IC50 7.17 7.17 68.4 1
Bcl-2-like protein 2
CHEMBL4677
IC50 7.16 7.16 70.0 1
HEL
CHEMBL613888
EC50 7.16 7.16 70.0 1
NB17
CHEMBL2366064
IC50 7.15 7.15 71.2 1
SK-NEP-1
CHEMBL1075580
IC50 7.14 7.14 72.1 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 6101.18 ng.hr.mL-1 Rattus norvegicus
AUC 55261.52 ng.hr.mL-1 Mus musculus
AUC 27094.71 ng.hr.mL-1 Canis lupus familiaris
AUC 6442.3 ng.hr.mL-1 Macaca fascicularis
CL 9.77 uL.min-1.(10^6cells)-1 Rattus norvegicus
F 20.0 % Mus musculus
F 20.0 % Canis lupus familiaris
F 20.0 % Macaca fascicularis
F 20.0 % Rattus norvegicus
F 20.0 % Rattus norvegicus
F 48.0 % Canis lupus familiaris
F 57.0 % Mus musculus
T1/2 4.0 hr Rattus norvegicus
T1/2 4.0 hr Mus musculus
T1/2 4.0 hr Canis lupus familiaris
T1/2 4.0 hr Macaca fascicularis

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Apoptosis regulator Bcl-2 Ki = 0.044 nM 10.36 Inhibition of Bcl2 (unknown origin) 28926247
Apoptosis regulator Bcl-2 Ki = 0.044 nM 10.36 Inhibition of Bcl2 (unknown origin) 31188592
Apoptosis regulator Bcl-2 Ki = 0.044 nM 10.36 Binding affinity to Bcl-2 (unknown origin) assessed as dissociation constant inc... 25787766
Bcl-2-like protein 1 Ki = 0.055 nM 10.26 Inhibition of Bcl-xL (unknown origin) 28926247
Bcl-2-like protein 1 Ki = 0.055 nM 10.26 Binding affinity to Bcl-xl (unknown origin) assessed as dissociation constant in... 25787766
Apoptosis regulator Bcl-2 Kd = 0.65 nM 9.19 Displacement of biotin-tagged MRPEPATIAQELRRIGDEFNA from C-terminal His-tagged h... 34533954
Apoptosis regulator Bcl-2 IC50 = 2.0 nM 8.7 Inhibition of recombinant human C-terminal 6xHis-tagged Bcl-2 (M1 to F212 residu... 31606346
Bcl-2-like protein 1 Kd = 2.07 nM 8.68 Displacement of biotin-tagged LWAAQRYGRELRRMSDEFEGSFKGL from human BCL-XL expres... 34533954
Bcl-2-like protein 1 IC50 = 3.3 nM 8.48 Displacement of FITC-Bid from GST-tagged human Bcl-xL expressed in Escherichia c... 24215352
NON-PROTEIN TARGET EC50 = 4.2 nM 8.38 Cytotoxicity against IL3-dependent mouse FL5.12 cells overexpressing human Bcl-X... 18841882
Bcl-xL/Bcl-2-like protein 11 IC50 = 4.3 nM 8.37 Inhibition of Bcl-xL/Bim (unknown origin) by ELISA 25437618
NON-PROTEIN TARGET EC50 = 5.9 nM 8.23 Cytotoxicity against IL3-dependent mouse FL5.12 cells overexpressing human Bcl2 ... 18841882
EOL1 IC50 = 6.693 nM 8.17 SANGER: Inhibition of human EoL-1-cell cell growth in a cell viability assay. -
Bcl-2-like protein 1 IC50 = 8.2 nM 8.09 Displacement of Bad-derived peptide from Bcl-XL (unknown origin) by fluorescence... 29229225
Unchecked IC50 = 8.2 nM 8.09 Inhibition of GST fused Bcl-xL (unknown origin) incubated for 5 min by TR-FRET a... 37713805
Apoptosis regulator Bcl-2 IC50 = 10.3 nM 7.99 Displacement of Bax-derived peptide from Bcl-2 (unknown origin) by fluorescence ... 29229225
Apoptosis regulator Bcl-2 IC50 = 10.3 nM 7.99 Inhibition of Bcl-2 (unknown origin) by fluorescence polarization assay 37713805
OCI-AML2 EC50 = 11.0 nM 7.96 Antiproliferative activity against human OCI-AML2 assessed as reduction in cell ... 25787766
SIG-M5 EC50 = 11.0 nM 7.96 Antiproliferative activity against human SIG-M5 assessed as reduction in cell vi... 25787766
EOL1 EC50 = 11.0 nM 7.96 Antiproliferative activity against human EOL1 assessed as reduction in cell viab... 25787766

Literature References

PubMed DOI Target Context # Activities
25787766 10.1126/scitranslmed.aaa4642 Unchecked 16
26288699 10.1021/acsmedchemlett.5b00128 NON-PROTEIN TARGET 8
33069066 10.1016/j.bmc.2020.115675 Aspartyl/asparaginyl beta-hydroxylase 5
18841882 10.1021/jm800669s NON-PROTEIN TARGET 4
23030453 10.1021/jm3010306 NCI-H146 4
25787766 10.1126/scitranslmed.aaa4642 ZR-75-1 4
25787766 10.1126/scitranslmed.aaa4642 MDA-MB-231 4
18841882 10.1021/jm800669s Mus musculus 4
18841882 10.1021/jm800669s Rattus norvegicus 4
- 10.6019/CHEMBL4651402 SARS-CoV-2 4
18841882 10.1021/jm800669s Cynomolgus monkey 3
18841882 10.1021/jm800669s Canis familiaris 3
31606346 10.1016/j.bmcl.2019.126682 Bcl-2-like protein 1 3
25787766 10.1126/scitranslmed.aaa4642 MDA-MB-468 3
32388279 10.1016/j.ejmech.2020.112397 Unchecked 2
- 10.6019/CHEMBL4651402 Vero C1008 2
34533954 10.1021/acs.jmedchem.1c00517 von Hippel-Lindau disease tumor suppressor/Bcl-2-like protein 1 2
34533954 10.1021/acs.jmedchem.1c00517 Unchecked 2
22608961 10.1016/j.bmcl.2012.04.103 SUD4 2
33197310 10.1021/acs.jmedchem.0c01290 Apoptosis regulator Bcl-2 2

Data from ChEMBL 36 via Core Engine