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Compound Detail

CHEMBL3301610

ABEMACICLIB
💊 Approved Drug
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💊 Approved Drug
CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4cc(F)c5nc(C)n(C(C)C)c5c4)n3)nc2)CC1

Basic Information

ChEMBL ID CHEMBL3301610
Name ABEMACICLIB
Phase Approved
Structure Type MOL
InChI Key UZWDCWONPYILKI-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Abemaciclib Ly-2835219 LY2835219 Verzenio Verzenios
114
Targets
295
Activities
4
Assay Types
30
PK Parameters
20
Publications
5
Known Names
20
Indications
2
Mechanisms

Molecular Properties

506.6
MW (Da)
4.94
ALogP
8
HBA
1
HBD
75.0
PSA (Ų)
0.38
QED
1
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2017
Availability Prescription
Chirality Achiral

Routes of Administration

Oral

Flags

Chemical Probe
USAN Stem -ciclib
USAN Year 2014

Extended Properties

Molecular Formula C27H32F2N8
MW 506.61
Aromatic Rings 4
Heavy Atoms 37
NP-Likeness -1.56

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Cyclin-dependent kinase 4 inhibitor INHIBITOR Cyclin-dependent kinase 4
Cyclin-dependent kinase 6 inhibitor INHIBITOR Cyclin-dependent kinase 6

Indications

Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Neoplasms Neoplasms Carcinoma, Non-Small-Cell Lung Liposarcoma Biliary Tract Neoplasms Brain Neoplasms Breast Neoplasms, Male Carcinoma, Hepatocellular Carcinoma, Pancreatic Ductal Carcinoma, Squamous Cell Endometrial Neoplasms Genital Neoplasms, Female Glioblastoma Head and Neck Neoplasms Hemangiosarcoma Lung Neoplasms

ATC Classification

L01EF03
abemaciclib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 237 meas. best 9.59
Kd 39 meas. best 9.07
Ki 10 meas. best 9.22
EC50 9 meas. best 7.7

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Cyclin-dependent kinase 4
CHEMBL331
IC50 9.59 8.7425 0.3 12
CDK6/cyclin D1
CHEMBL2111455
IC50 9.37 8.5067 0.4 6
Cyclin-dependent kinase 4/cyclin D1
CHEMBL1907601
IC50 9.34 8.7018 0.5 11
Cyclin-dependent kinase 4/cyclin D1
CHEMBL1907601
Ki 9.22 9.0467 0.6 3
Dual specificity protein kinase CLK1
CHEMBL4224
Kd 9.07 8.61 0.9 2
CDK4/Cyclin D3
CHEMBL3038472
IC50 8.82 8.2275 1.5 8
Cyclin-dependent kinase 6
CHEMBL2508
IC50 8.72 8.0671 1.9 14
Cyclin-dependent kinase 4/G1/S-specific cyclin-E1
CHEMBL3885554
IC50 8.7 8.265 2.0 2
Unchecked
CHEMBL612545
IC50 8.7 7.1775 2.0 8
CDK6/cyclin D1
CHEMBL2111455
Ki 8.62 8.31 2.4 2
Calcium/calmodulin-dependent protein kinase type II subunit delta
CHEMBL2801
IC50 8.59 8.59 2.6 1
Dual specificity tyrosine-phosphorylation-regulated kinase 1A
CHEMBL2292
Kd 8.47 7.58 3.3 2
Calcium/calmodulin-dependent protein kinase type II subunit beta
CHEMBL4121
IC50 8.46 8.46 3.5 1
Dual specificity tyrosine-phosphorylation-regulated kinase 1B
CHEMBL5543
IC50 8.46 8.175 3.5 2
CDK6/cyclin D3
CHEMBL2111448
IC50 8.42 7.928 3.8 10
Serine/threonine-protein kinase pim-1
CHEMBL2147
IC50 8.41 7.855 3.9 4
Unchecked
CHEMBL612545
Kd 8.4 8.4 4.0 1
Cyclin-dependent kinase 1/ G1/S-specific cyclin-D3
CHEMBL4296065
IC50 8.29 8.03 5.1 4
Serine/threonine-protein kinase pim-1
CHEMBL2147
Kd 8.15 8.15 7.0 1
Glycogen synthase kinase-3 beta
CHEMBL262
Kd 8.12 8.005 7.7 2
CDK6/cyclin D3
CHEMBL2111448
Ki 8.09 8.09 8.2 1
Glycogen synthase kinase-3 beta
CHEMBL262
IC50 8.06 7.1725 8.7 4
Glycogen synthase kinase-3 alpha
CHEMBL2850
Kd 7.89 7.89 13.0 1
Dual specificity protein kinase CLK4
CHEMBL4203
Kd 7.89 7.89 13.0 1
Dual specificity tyrosine-phosphorylation-regulated kinase 1A
CHEMBL2292
IC50 7.79 7.635 16.3 2
Calcium/calmodulin-dependent protein kinase type II subunit gamma
CHEMBL3829
Kd 7.75 7.75 18.0 1
Calcium/calmodulin-dependent protein kinase type II subunit delta
CHEMBL2801
Kd 7.72 7.72 19.0 1
Casein kinase II subunit alpha'
CHEMBL4070
Kd 7.72 7.72 19.0 1
MDA-MB-361
CHEMBL614129
EC50 7.7 7.7 20.0 1
Dual specificity tyrosine-phosphorylation-regulated kinase 3
CHEMBL4575
IC50 7.69 7.69 20.6 1
Cyclin-dependent kinase 4/6
CHEMBL3885553
IC50 7.66 7.276 22.0 5
Dual specificity tyrosine-phosphorylation-regulated kinase 2
CHEMBL4376
IC50 7.59 7.3367 25.4 3
Homeodomain-interacting protein kinase 2
CHEMBL4576
IC50 7.51 7.51 31.0 2
CDK9/cyclin T1
CHEMBL2111389
IC50 7.46 7.1629 34.6 7
Cyclin-dependent kinase 9
CHEMBL3116
IC50 7.46 6.905 34.5 4
T47D
CHEMBL614361
IC50 7.46 7.15 34.3 2
CDK2/Cyclin A2
CHEMBL3038469
IC50 7.41 7.19 39.0 5
AarF domain-containing protein kinase 1
CHEMBL4105885
Kd 7.4 7.4 40.0 1
U-87 MG
CHEMBL614247
IC50 7.32 6.54 48.1 3
Cyclin-dependent kinase 16
CHEMBL4597
Kd 7.3 7.3 50.0 1
Serine/threonine-protein kinase ICK
CHEMBL1163126
Kd 7.28 7.28 53.0 1
Cyclin-dependent kinase 2
CHEMBL301
IC50 7.28 6.895 52.2 4
Calcium/calmodulin-dependent protein kinase type II subunit gamma
CHEMBL3829
IC50 7.28 7.28 52.0 1
CDK1/Cyclin A
CHEMBL3038467
IC50 7.25 7.25 56.0 1
CDK9/cyclin T1
CHEMBL2111389
Ki 7.24 7.24 57.0 1
Cyclin-dependent kinase 6
CHEMBL2508
Kd 7.23 7.23 59.0 1
MDA-MB-231
CHEMBL400
IC50 7.21 6.37 62.0 4
CDK9/Cyclin K
CHEMBL3038475
IC50 7.19 7.19 65.0 1
Dual specificity protein kinase CLK1
CHEMBL4224
IC50 7.19 7.14 64.7 2
COLO 205
CHEMBL614561
EC50 7.14 7.14 72.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 3275.0 ng.hr.mL-1 Rattus norvegicus
AUC 179.5 ng.hr.mL-1 Mus musculus
AUC 225.9 ng.hr.mL-1 Mus musculus
AUC 830.0 ng.hr.mL-1 Mus musculus
AUC 2174.0 ng.hr.mL-1 Mus musculus
AUC 487.2 ng.hr.mL-1 Mus musculus
AUC 451.39 ng.hr.mL-1 Mus musculus
CL 24.0 mL.min-1.g-1 Rattus norvegicus
CL 50.0 mL.min-1.g-1 Homo sapiens
CL 137.0 mL.min-1.g-1 Mus musculus
CL 44.71 mL.min-1.kg-1 Mus musculus
CL 60.0 mL.min-1.kg-1 Mus musculus
CL 172.13 mL.min-1.kg-1 Homo sapiens
CL 62.91 mL.min-1.kg-1 Rattus norvegicus
CL 42.96 mL.min-1.kg-1 Mus musculus
CL 32.9 mL.min-1.kg-1 Mus musculus
Cmax 615.86 nM Rattus norvegicus
Cmax 434.26 nM Mus musculus
Cmax 83.5 nM Mus musculus
Cmax 1510.04 nM Mus musculus
Cmax 1138.94 nM Mus musculus
Cmax 226.0 nM Mus musculus
F 62.9 % Mus musculus
F 78.6 % Mus musculus
F 48.4 % Mus musculus
F 45.0 % Homo sapiens
MRT 7.97 hr Rattus norvegicus
T1/2 4.07 hr Rattus norvegicus
T1/2 1.483 hr Rattus norvegicus
T1/2 0.7 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Cyclin-dependent kinase 4 IC50 = 0.26 nM 9.59 CDK4 Inhibition Assay: Test compounds (compound of the present invention, refere... -
Cyclin-dependent kinase 4 IC50 = 0.26 nM 9.59 CDK4 Inhibition Assay: Test compounds (compound of the present invention, refere... -
CDK6/cyclin D1 IC50 = 0.43 nM 9.37 Inhibition of human CDK6/cyclin D1 preincubated with compound for 20 mins follow... 29133594
Cyclin-dependent kinase 4/cyclin D1 IC50 = 0.46 nM 9.34 Inhibition of human CDK4/cyclin D1 preincubated with compound for 20 mins follow... 29133594
Cyclin-dependent kinase 4/cyclin D1 Ki = 0.6 nM 9.22 Competitive inhibition of human CDK4/cyclin D1 expressed in insect cells assesse... 26115571
Cyclin-dependent kinase 4/cyclin D1 IC50 = 0.6 nM 9.22 Inhibition of CDK4/cyclin D1 (unknown origin) 29133594
Cyclin-dependent kinase 4/cyclin D1 Ki = 0.6 nM 9.22 ATP competitive inhibition of recombinant human N-terminal GST-fused CDK4 (S4 to... 24919854
Dual specificity protein kinase CLK1 Kd = 0.851 nM 9.07 Binding affinity to human CLK1 assessed as equilibrium dissociation constant mea... 36876904
Cyclin-dependent kinase 4/cyclin D1 IC50 = 1.07 nM 8.97 Inhibition of CDK4/Cyclin D1 (unknown origin) 38670537
CDK6/cyclin D1 IC50 = 1.26 nM 8.9 Inhibition of CDK6/Cyclin D1 (unknown origin) 38670537
CDK4/Cyclin D3 IC50 = 1.5 nM 8.82 Inhibition of recombinant N-terminal GST/His6-fusion tagged human CDK4/Cyclin D3... 35447031
Cyclin-dependent kinase 4 IC50 = 1.7 nM 8.77 Inhibition of CDK4 (unknown origin) after 90 mins by ADP-Glo assay 29429832
CDK4/Cyclin D3 IC50 = 1.8 nM 8.74 Inhibition of recombinant human full-length N-terminal GST-fused CDK4 (1 to 303 ... 32200202
CDK4/Cyclin D3 IC50 = 1.82 nM 8.74 Inhibition of recombinant human full length N-terminal GST-tagged CDK4 (1 to 303... 31200237
Cyclin-dependent kinase 6 IC50 = 1.9 nM 8.72 Inhibition of CDK6 (unknown origin) using U-light as substrate preincubated for ... 29074254
Cyclin-dependent kinase 4 IC50 = 1.9 nM 8.72 Inhibition of CDK4 (unknown origin) using U-light as substrate preincubated for ... 29074254
Cyclin-dependent kinase 4 IC50 = 2.0 nM 8.7 Inhibition of CDK4 (unknown origin) 30639897
Cyclin-dependent kinase 4 IC50 = 2.0 nM 8.7 Inhibition of CDK4 (unknown origin) 30978559
Cyclin-dependent kinase 4 IC50 = 2.0 nM 8.7 Inhibition of human CDK4 incubated for 18 hrs by microscopic analysis 33650861
Unchecked IC50 = 2.0 nM 8.7 Inhibition of CDK4/cyclin D (unknown origin) 35485642

Literature References

PubMed DOI Target Context # Activities
24919854 10.1007/s10637-014-0120-7 Unchecked 41
24919854 10.1007/s10637-014-0120-7 MV4-11 29
24919854 10.1007/s10637-014-0120-7 COLO 205 24
29133594 10.1158/1541-7786.mcr-17-0468 Glycogen synthase kinase-3 beta 22
31200237 10.1016/j.ejmech.2019.06.005 ADMET 19
24919854 10.1007/s10637-014-0120-7 ADMET 17
30978559 10.1016/j.ejmech.2019.03.064 ADMET 16
29133594 10.1158/1541-7786.mcr-17-0468 Calcium/calmodulin-dependent protein kinase type II subunit gamma 16
29133594 10.1158/1541-7786.mcr-17-0468 Serine/threonine-protein kinase 24 16
34875521 10.1016/j.ejmech.2021.114024 RPMI-8226 13
29133594 10.1158/1541-7786.mcr-17-0468 Serine/threonine-protein kinase MARK2 12
29133594 10.1158/1541-7786.mcr-17-0468 Calcium/calmodulin-dependent protein kinase type II subunit delta 12
29133594 10.1158/1541-7786.mcr-17-0468 Mitogen-activated protein kinase 8 12
29133594 10.1158/1541-7786.mcr-17-0468 Mitogen-activated protein kinase 14 12
29133594 10.1158/1541-7786.mcr-17-0468 Casein kinase I isoform alpha 12
29133594 10.1158/1541-7786.mcr-17-0468 Glycogen synthase kinase-3 alpha 12
- 10.6019/CHEMBL5303304 HEK-293T 10
29133594 10.1158/1541-7786.mcr-17-0468 Casein kinase II subunit alpha 10
29133594 10.1158/1541-7786.mcr-17-0468 Serine/threonine-protein kinase 10 9
29133594 10.1158/1541-7786.mcr-17-0468 Serine/threonine-protein kinase D3 9

Data from ChEMBL 36 via Core Engine