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Compound Detail

CHEMBL5095094

CULMERCICLIB
🧪 Phase II
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🧪 Phase II
CC(C)c1c2cc(-c3nc(Nc4ccc(N5CCNCC5)cn4)ncc3F)ccc2nn1C

Basic Information

ChEMBL ID CHEMBL5095094
Name CULMERCICLIB
Phase Phase II
Structure Type MOL
InChI Key LLFOBMRPWNABCB-UHFFFAOYSA-N

Known Names

Culmerciclib
16
Targets
18
Activities
1
Assay Types
25
PK Parameters
20
Publications
1
Known Names
1
Indications

Molecular Properties

446.5
MW (Da)
3.84
ALogP
8
HBA
2
HBD
83.8
PSA (Ų)
0.48
QED
0
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral
USAN Stem -ciclib

Extended Properties

Molecular Formula C24H27FN8
MW 446.53
Aromatic Rings 4
Heavy Atoms 33
NP-Likeness -1.42

Indications

Neoplasms

Activity Summary

IC50 18 meas. best 9.46

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Cyclin-dependent kinase 4/cyclin D1
CHEMBL1907601
IC50 9.46 8.87 0.3 2
CDK6/cyclin D1
CHEMBL2111455
IC50 9.31 8.265 0.5 2
Cyclin-dependent kinase 6
CHEMBL2508
IC50 8.62 8.62 2.4 1
Cyclin-dependent kinase 2
CHEMBL301
IC50 8.62 8.62 2.4 1
Cyclin-dependent kinase 4
CHEMBL331
IC50 8.62 8.62 2.4 1
Unchecked
CHEMBL612545
IC50 8.62 8.62 2.4 1
CDK9/cyclin T1
CHEMBL2111389
IC50 7.9 7.9 12.5 1
MCF7
CHEMBL387
IC50 7.49 7.49 32.1 1
Cyclin-dependent kinase 5/CDK5 activator 1
CHEMBL1907600
IC50 7.45 7.45 35.3 1
Cyclin-dependent kinase 1/cyclin B1
CHEMBL1907602
IC50 6.61 6.61 246.0 1
MDA-MB-436
CHEMBL4296465
IC50 6.32 6.32 484.0 1
Cyclin-dependent kinase 2/cyclin E1
CHEMBL1907605
IC50 6.25 6.25 556.0 1
CDK1/Cyclin E
CHEMBL3038468
IC50 5.68 5.68 2092.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.28 5.28 5300.0 1
Cytochrome P450 2C19
CHEMBL3622
IC50 5.03 5.03 9330.0 1
Cytochrome P450 2C9
CHEMBL3397
IC50 4.64 4.64 23000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 610.41 ng.hr.mL-1 Mus musculus
AUC 2625.6 ng.hr.mL-1 Rattus norvegicus
AUC 553.7 ng.hr.mL-1 Canis lupus familiaris
CL 0.1164 mL.min-1.kg-1 Mus musculus
CL 0.0378 mL.min-1.kg-1 Rattus norvegicus
CL 0.0386 mL.min-1.kg-1 Canis lupus familiaris
CL 0.0489 mL.min-1.kg-1 Macaca mulatta
CL 0.0125 mL.min-1.kg-1 Homo sapiens
CL 31.3 mL.min-1.kg-1 Mus musculus
CL 30.4 mL.min-1.kg-1 Rattus norvegicus
CL 32.0 mL.min-1.kg-1 Canis lupus familiaris
Cmax 248.0 nM Mus musculus
Cmax 415.0 nM Rattus norvegicus
Cmax 109.0 nM Canis lupus familiaris
F 65.0 % Mus musculus
F 74.9 % Rattus norvegicus
F 56.0 % Canis lupus familiaris
Fu 0.026 - Mus musculus
Fu 0.025 - Rattus norvegicus
Fu 0.051 - Canis lupus familiaris
Fu 0.061 - Macaca mulatta
Fu 0.08 - Homo sapiens
T1/2 2.3 hr Mus musculus
T1/2 4.2 hr Rattus norvegicus
T1/2 7.8 hr Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Cyclin-dependent kinase 4/cyclin D1 IC50 = 0.35 nM 9.46 Inhibition of CDK4/Cyclin D1 (unknown origin) 38670537
CDK6/cyclin D1 IC50 = 0.49 nM 9.31 Inhibition of CDK6/Cyclin D1 (unknown origin) 38670537
Cyclin-dependent kinase 2 IC50 = 2.4 nM 8.62 Inhibition of CDK2 (unknown origin) 38569434
Cyclin-dependent kinase 4 IC50 = 2.4 nM 8.62 Inhibition of CDK4 (unknown origin) 38569434
Cyclin-dependent kinase 6 IC50 = 2.4 nM 8.62 Inhibition of CDK6 (unknown origin) 38569434
Unchecked IC50 = 2.4 nM 8.62 Inhibition of CDK2/Cyclin A (unknown origin) 38670537
Cyclin-dependent kinase 4/cyclin D1 IC50 = 5.2 nM 8.28 Inhibition of CDK4/Cyclin D1 (unknown origin) transfected in HEK293 cells by Nan... 38670537
CDK9/cyclin T1 IC50 = 12.5 nM 7.9 Inhibition of CDK9/cyclin T1 (unknown origin) in presence of 33P-gamma-ATP by sc... 38670537
MCF7 IC50 = 32.1 nM 7.49 Antiproliferative activity against Rb-proficient human MCF7 cells assessed as in... 38670537
Cyclin-dependent kinase 5/CDK5 activator 1 IC50 = 35.3 nM 7.45 Inhibition of CDK5/p25 (unknown origin) in presence of 33P-gamma-ATP by scintill... 38670537
CDK6/cyclin D1 IC50 = 60.3 nM 7.22 Inhibition of CDK6/Cyclin D1 (unknown origin) transfected in HEK293 cells by Nan... 38670537
Cyclin-dependent kinase 1/cyclin B1 IC50 = 246.0 nM 6.61 Inhibition of CDK1/cyclin B (unknown origin) in presence of 33P-gamma-ATP by sci... 38670537
MDA-MB-436 IC50 = 484.0 nM 6.32 Antiproliferative activity against Rb-deficient human MDA-MB-436 cells assessed ... 38670537
Cyclin-dependent kinase 2/cyclin E1 IC50 = 556.0 nM 6.25 Inhibition of CDK2/Cyclin E1 (unknown origin) transfected in HEK293 cells by Nan... 38670537
CDK1/Cyclin E IC50 = 2092.0 nM 5.68 Inhibition of CDK1/Cyclin E1 (unknown origin) transfected in HEK293 cells by Nan... 38670537
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 5300.0 nM 5.28 Inhibition of hERG 38670537
Cytochrome P450 2C19 IC50 = 9330.0 nM 5.03 Inhibition of CYP2C19 (unknown origin) using midazolam as substrate 38670537
Cytochrome P450 2C9 IC50 = 23000.0 nM 4.64 Inhibition of CYP2C9 (unknown origin) using midazolam as substrate 38670537

Literature References

PubMed DOI Target Context # Activities
38670537 10.1016/j.bmcl.2024.129769 ADMET 34
38670537 10.1016/j.bmcl.2024.129769 Unchecked 6
38670537 10.1016/j.bmcl.2024.129769 MCF7 6
38670537 10.1016/j.bmcl.2024.129769 MDA-MB-436 4
38670537 10.1016/j.bmcl.2024.129769 Retinoblastoma-associated protein 3
38670537 10.1016/j.bmcl.2024.129769 No relevant target 2
38670537 10.1016/j.bmcl.2024.129769 Cyclin-dependent kinase 4/cyclin D1 2
38670537 10.1016/j.bmcl.2024.129769 CDK6/cyclin D1 2
38670537 10.1016/j.bmcl.2024.129769 Cyclin-dependent kinase 1/cyclin B1 1
38670537 10.1016/j.bmcl.2024.129769 SNU1 1
38670537 10.1016/j.bmcl.2024.129769 MKN-45 1
38670537 10.1016/j.bmcl.2024.129769 NCI-H460 1
38670537 10.1016/j.bmcl.2024.129769 NCI-H1299 1
38670537 10.1016/j.bmcl.2024.129769 T47D 1
38670537 10.1016/j.bmcl.2024.129769 CDK9/cyclin T1 1
38670537 10.1016/j.bmcl.2024.129769 Cyclin-dependent kinase 5/CDK5 activator 1 1
38569434 10.1016/j.ejmech.2024.116333 Cyclin-dependent kinase 2 1
38670537 10.1016/j.bmcl.2024.129769 Cytochrome P450 1A2 1
38670537 10.1016/j.bmcl.2024.129769 Cyclin-dependent kinase 2/cyclin E1 1
38569434 10.1016/j.ejmech.2024.116333 Cyclin-dependent kinase 6 1

Data from ChEMBL 36 via Core Engine