Compound Detail

CHEMBL428690

ALVOCIDIB

🧪 Phase III

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🧪 Phase III

CN1CC[C@H](c2c(O)cc(O)c3c(=O)cc(-c4ccccc4Cl)oc23)[C@H](O)C1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL428690
Name	ALVOCIDIB
Phase	Phase III
Structure Type	MOL
InChI Key	BIIVYFLTOXDAOV-YVEFUNNKSA-N

Known Names

Alvocidib Alvocidib freebase Flavopiridol HL 275 HL-275 HMR 1275 HMR-1275 L 86 8275 L-868275 L86-8275 MDL 107,826A MDL-107826A +1 more

219

Targets

602

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

401.9

MW (Da)

3.30

ALogP

HBA

HBD

94.1

PSA (Å²)

0.61

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Single Enantiomer

Flags

Natural Product

USAN Year

2010

Extended Properties

Molecular Formula	C21H20ClNO5
MW	401.85
Aromatic Rings	3
Heavy Atoms	28
NP-Likeness	0.84

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Cyclin-dependent kinase 2 inhibitor	INHIBITOR	Cyclin-dependent kinase 2	✓	✓
Cyclin-dependent kinase 4 inhibitor	INHIBITOR	Cyclin-dependent kinase 4	✓	✓
Cyclin-dependent kinase 6 inhibitor	INHIBITOR	Cyclin-dependent kinase 6	✓	✓
Cyclin-dependent kinase 9 inhibitor	INHIBITOR	Cyclin-dependent kinase 9	✓	✓
Cyclin-dependent kinase 1 inhibitor	INHIBITOR	Cyclin-dependent kinase 1	✓	✓
Cyclin-dependent kinase 7 inhibitor	INHIBITOR	Cyclin-dependent kinase 7	✓	✓

Indications

Endometrial Neoplasms Esophageal Neoplasms Kidney Neoplasms Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Myeloid, Acute Leukemia, Prolymphocytic Liver Neoplasms Lymphoma Melanoma Multiple Myeloma Pancreatic Neoplasms Prostatic Neoplasms, Castration-Resistant Sarcoma Breast Neoplasms Breast Neoplasms, Male Hematologic Neoplasms Leukemia Leukemia, Lymphoid Neoplasms

Activity Summary

Kd 314 meas. best 9.16

IC50 265 meas. best 8.6

EC50 12 meas. best 7.82

Ki 11 meas. best 8.52

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Serine/threonine-protein kinase ICK CHEMBL1163126	Kd	9.16	9.16	0.7	1
CDK9/cyclin T1 CHEMBL2111389	IC50	8.6	7.9946	2.5	13
CDK9/cyclin T1 CHEMBL2111389	Ki	8.52	8.52	3.0	1
Cyclin-dependent kinase 9 CHEMBL3116	IC50	8.52	7.918	3.0	15
Cyclin-dependent kinase 9 CHEMBL3116	Ki	8.52	8.52	3.0	1
La-related protein 7 CHEMBL4523314	Ki	8.52	8.52	3.0	1
Cyclin-dependent kinase 4 CHEMBL331	Kd	8.48	8.265	3.3	2
Cyclin-dependent kinase 17 CHEMBL5790	Kd	8.22	6.9533	6.0	3
Cyclin-dependent kinase 9 CHEMBL3116	Kd	8.19	8.1767	6.4	3
Cyclin-dependent kinase-like 5 CHEMBL1163112	Kd	8.15	8.15	7.1	1
NON-PROTEIN TARGET CHEMBL3879801	IC50	8.15	7.425	7.0	2
Cyclin-dependent kinase 2 CHEMBL301	IC50	8.0	6.9812	10.0	17
Cyclin-dependent kinase 7 CHEMBL3055	IC50	8.0	7.2567	10.0	6
Cyclin-dependent kinase 1 CHEMBL308	IC50	8.0	7.5613	10.0	16
Cyclin-dependent kinase 4 CHEMBL331	IC50	8.0	7.1133	10.0	15
Unchecked CHEMBL612545	IC50	7.92	6.7636	12.0	22
Human immunodeficiency virus 1 CHEMBL378	EC50	7.82	7.82	15.0	1
LNCaP CHEMBL612518	IC50	7.8	7.8	16.0	1
HCT-116 CHEMBL394	IC50	7.77	7.2183	17.0	6
Calcium/calmodulin-dependent protein kinase kinase 1 CHEMBL5256	Kd	7.72	7.3067	19.0	3
Cyclin-dependent kinase 4/cyclin D1 CHEMBL1907601	IC50	7.7	7.0142	20.0	12
Cyclin-dependent kinase 6 CHEMBL2508	IC50	7.7	7.2333	20.0	9
Cyclin-dependent kinase 7 CHEMBL3055	Kd	7.64	7.15	23.0	3
MCF7 CHEMBL387	IC50	7.58	6.8025	26.0	4
Cyclin-dependent kinase 1/cyclin B1 CHEMBL1907602	IC50	7.57	7.3189	27.0	9
Serine/threonine-protein kinase MAK CHEMBL1163106	Kd	7.55	7.55	28.0	1
Cyclin-dependent kinase 1/cyclin B CHEMBL2094127	IC50	7.52	7.0057	30.0	7
Unchecked CHEMBL612545	Kd	7.52	6.515	30.0	2
NON-PROTEIN TARGET CHEMBL3879801	EC50	7.47	7.35	34.0	2
Non-receptor tyrosine-protein kinase TYK2 CHEMBL3553	Kd	7.46	6.5567	35.0	3
A2780 CHEMBL614004	IC50	7.42	6.87	38.0	7
Cyclin-dependent kinase 2 CHEMBL301	Ki	7.4	7.06	40.0	2
Cyclin-dependent kinase 1 CHEMBL308	Ki	7.4	7.28	40.0	2
Cyclin-dependent kinase 4 CHEMBL331	Ki	7.4	7.4	40.0	1
Cyclin-dependent kinase 1/cyclin B1 CHEMBL1907602	Ki	7.39	7.39	41.0	1
Cyclin-dependent kinase 5 CHEMBL4036	Kd	7.37	7.065	43.0	4
ABAE CHEMBL613546	IC50	7.35	7.35	45.0	1
HL-60 CHEMBL383	IC50	7.34	7.34	46.0	1
HS27 CHEMBL614666	IC50	7.29	7.29	51.0	1
CCRF-CEM CHEMBL382	IC50	7.28	7.28	52.0	1
OVCAR-3 CHEMBL614213	IC50	7.27	7.27	54.0	1
Cyclin-dependent kinase 4/6 CHEMBL3885553	EC50	7.26	7.26	55.0	1
Serine/threonine-protein kinase TNNI3K CHEMBL5260	Kd	7.26	7.26	55.0	2
Cyclin-dependent kinase 19 CHEMBL6002	Kd	7.24	7.24	57.0	2
Eukaryotic translation initiation factor 2-alpha kinase 1 CHEMBL6029	Kd	7.24	6.65	58.0	2
HCT-116 CHEMBL394	EC50	7.23	7.23	59.0	1
Cyclin-dependent kinase 5/CDK5 activator 1 CHEMBL1907600	IC50	7.22	6.866	60.0	5
MDA-MB-231 CHEMBL400	IC50	7.22	7.22	60.0	1
Serine/threonine-protein kinase VRK2 CHEMBL1649059	Kd	7.2	7.2	63.0	1
Unchecked CHEMBL612545	Ki	7.19	7.19	65.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	5304.42	ng.hr.mL-1	Mus musculus
CL	6.1	mL.min-1.kg-1	Homo sapiens
Cmax	6900.0	nM	Mus musculus
Fu	0.06	-	Homo sapiens
Fu	0.0442	-	Rattus norvegicus
Fu	1.0	-	Rattus norvegicus
Fu	0.147	-	Rattus norvegicus
Fu	0.0624	-	Rattus norvegicus
Fu	0.021	-	Rattus norvegicus
Fu	0.033	-	Rattus norvegicus
Fu	0.051	-	Rattus norvegicus
Fu	0.057	-	Rattus norvegicus
MRT	2.0	hr	Mus musculus
MRT	4.0	hr	Homo sapiens
T1/2	1.1	hr	Mus musculus
T1/2	5.2	hr	Homo sapiens
Tmax	0.5	hr	Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Serine/threonine-protein kinase ICK	Kd	=	0.69	nM	9.16	Binding constant for ICK kinase domain	22037378
CDK9/cyclin T1	IC50	=	2.5	nM	8.6	Inhibition of human His6-tagged CDK9/cyclin T1 expressed in baculovirus infected...	27171036
Cyclin-dependent kinase 9	IC50	=	3.0	nM	8.52	Inhibition of CDK9 (unknown origin)	37234044
Cyclin-dependent kinase 9	IC50	=	3.0	nM	8.52	Inhibition of CDK9 (unknown origin)	35814933
Cyclin-dependent kinase 9	IC50	=	3.0	nM	8.52	Inhibition of CDK9 (unknown origin)	32866383
CDK9/cyclin T1	Ki	=	3.0	nM	8.52	Inhibition of CDK9/Cyclin T (1 to 330 amino acid residues) (unknown origin) by d...	23252711
Cyclin-dependent kinase 9	Ki	=	3.0	nM	8.52	Inhibition of CDK9 (unknown origin)	23252711
La-related protein 7	Ki	=	3.0	nM	8.52	Inhibition of human recombinant P-TEFb expressed in baculovirus expression syste...	30733087
Cyclin-dependent kinase 4	Kd	=	3.3	nM	8.48	Binding constant for CDK4-cyclinD3 kinase domain	22037378
CDK9/cyclin T1	IC50	=	3.7	nM	8.43	Inhibition of CDK9/cyclin T (unknown origin) using YSPTSPSYSPTSPSYSPTSPKKK as su...	29144137
Cyclin-dependent kinase 9	IC50	=	4.5	nM	8.35	Inhibition of CDK9 (unknown origin) incubated for 10 mins	36087428
CDK9/cyclin T1	IC50	=	4.59	nM	8.34	Inhibition of CDK9/Cyclin-T1 (unknown origin) using UlightCFFKNIVTPRTPPPSQGK-ami...	25914804
CDK9/cyclin T1	IC50	=	5.0	nM	8.3	Inhibition of CDK9/Cyclin T1 (unknown origin) using ULight MBP peptide as substr...	24102143
CDK9/cyclin T1	IC50	=	6.0	nM	8.22	Inhibition of CDK9/CycT1 (unknown origin)	24742150
CDK9/cyclin T1	IC50	=	6.0	nM	8.22	Inhibition of CDK9/Cyclin T (unknown origin)	19169685
Cyclin-dependent kinase 17	Kd	=	6.0	nM	8.22	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Cyclin-dependent kinase 9	IC50	=	6.1	nM	8.21	Inhibition of CDK9 (unknown origin) in presence of ATP by ADP-Glo kinase assay	37672930
Cyclin-dependent kinase 9	Kd	=	6.4	nM	8.19	Binding constant for full-length CDK9	18183025
Cyclin-dependent kinase 9	Kd	=	6.4	nM	8.19	Binding constant for CDK9 kinase domain	22037378
Cyclin-dependent kinase 9	Kd	=	7.0	nM	8.15	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878

Literature References

PubMed	DOI	Target Context	# Activities
9677190	10.1126/science.281.5376.533	Saccharomyces cerevisiae	67
31732255	10.1016/j.ejmech.2019.111813	ADMET	19
-	10.1007/s00044-011-9867-y	Molecular identity unknown	16
22037378	10.1038/nbt.1990	Tyrosine-protein kinase ABL1	15
23301767	10.1021/jm301475f	A2780	14
22037378	10.1038/nbt.1990	Epidermal growth factor receptor	12
29407975	10.1016/j.ejmech.2018.01.004	KOPN-8	11
27363938	10.1016/j.bmcl.2016.06.046	No relevant target	10
22037378	10.1038/nbt.1990	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	10
18183025	10.1038/nbt1358	Epidermal growth factor receptor	10
24919854	10.1007/s10637-014-0120-7	COLO 205	10
12190313	10.1021/jm0201520	Cyclin-dependent kinase 2	10
24919854	10.1007/s10637-014-0120-7	U2OS	9
26254279	10.18632/oncotarget.4214	Unchecked	9
22037378	10.1038/nbt.1990	Mast/stem cell growth factor receptor Kit	8
-	10.1007/s00044-011-9867-y	NON-PROTEIN TARGET	8
24102143	10.1111/bph.12408	Unchecked	8
32402934	10.1016/j.ejmech.2020.112355	Unchecked	8
22037378	10.1038/nbt.1990	Receptor-type tyrosine-protein kinase FLT3	7
15711537	10.1038/nbt1068	Tyrosine-protein kinase ABL1	7

Data from ChEMBL 36 via Core Engine