Compound Detail

CHEMBL1944698

ZOTIRACICLIB

🧪 Phase II

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🧪 Phase II

CN1C/C=C/CCOc2cccc(c2)-c2ccnc(n2)Nc2cccc(c2)C1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL1944698
Name	ZOTIRACICLIB
Phase	Phase II
Structure Type	MOL
InChI Key	VXBAJLGYBMTJCY-NSCUHMNNSA-N

Known Names

Ex 45 EX45 SB-1317 Sb-1317 free base SB1317 Tg-02 Tg02 Zotiraciclib

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

372.5

MW (Da)

4.66

ALogP

HBA

HBD

50.3

PSA (Å²)

0.58

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Achiral

Flags

Natural Product

USAN Stem	-ciclib
USAN Year	2019

Extended Properties

Molecular Formula	C23H24N4O
MW	372.47
Aromatic Rings	3
Heavy Atoms	28
NP-Likeness	0.65

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Cyclin-dependent kinase 1 inhibitor	INHIBITOR	Cyclin-dependent kinase 1	✓	✓
Cyclin-dependent kinase 2 inhibitor	INHIBITOR	Cyclin-dependent kinase 2	✓	✓
Cyclin-dependent kinase 7 inhibitor	INHIBITOR	Cyclin-dependent kinase 7	✓	✓
Cyclin-dependent kinase 9 inhibitor	INHIBITOR	Cyclin-dependent kinase 9	✓	✓
Tyrosine-protein kinase receptor FLT3 inhibitor	INHIBITOR	Receptor-type tyrosine-protein kinase FLT3	✓	✓
Tyrosine-protein kinase JAK2 inhibitor	INHIBITOR	Tyrosine-protein kinase JAK2	✓	✓

Indications

Carcinoma, Hepatocellular Glioblastoma Gliosarcoma Hematologic Neoplasms Leukemia, Lymphocytic, Chronic, B-Cell Neoplasms Rectal Neoplasms

Activity Summary

Kd 47 meas. best 9.0

IC50 39 meas. best 8.7

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Cyclin-dependent kinase 9 CHEMBL3116	Kd	9.0	9.0	1.0	1
Cyclin-dependent kinase 9 CHEMBL3116	IC50	8.7	8.61	2.0	2
Cyclin-dependent kinase 5 CHEMBL4036	IC50	8.52	8.46	3.0	2
Cyclin-dependent kinase 2 CHEMBL301	IC50	8.52	7.9	3.0	4
CDK3/Cyclin E CHEMBL3038471	IC50	8.52	8.24	3.0	3
CDK7/Cyclin H/MNAT1 CHEMBL3038473	IC50	8.52	7.975	3.0	2
CDK9/Cyclin K CHEMBL3038475	IC50	8.52	8.52	3.0	1
Cyclin-dependent kinase 1 CHEMBL308	IC50	8.52	8.285	3.0	2
Cyclin-dependent kinase 5/CDK5 activator 1 CHEMBL1907600	IC50	8.4	8.4	4.0	1
Cyclin-dependent kinase 2/cyclin E1 CHEMBL1907605	IC50	8.3	8.3	5.0	1
Cyclin-dependent kinase 1/cyclin B1 CHEMBL1907602	IC50	8.05	8.05	9.0	1
Cyclin-dependent kinase 2/cyclin A CHEMBL2094128	IC50	7.89	7.89	13.0	1
CDK2/Cyclin A2 CHEMBL3038469	IC50	7.89	7.89	13.0	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	IC50	7.68	7.39	21.0	4
AarF domain-containing protein kinase 1 CHEMBL4105885	Kd	7.64	7.64	23.0	1
Ramos CHEMBL614629	IC50	7.48	7.48	33.0	1
Cyclin-dependent kinase 16 CHEMBL4597	Kd	7.46	7.46	35.0	1
Cyclin-dependent kinase 7 CHEMBL3055	IC50	7.43	7.43	37.0	1
Mitogen-activated protein kinase 7 CHEMBL5332	Kd	7.37	7.37	43.0	1
Mitogen-activated protein kinase 7 CHEMBL5332	IC50	7.37	7.37	43.0	1
HL-60 CHEMBL383	IC50	7.23	7.23	59.0	1
COLO 205 CHEMBL614561	IC50	7.14	7.14	72.0	1
Tyrosine-protein kinase JAK2 CHEMBL2971	IC50	7.14	7.066	73.0	5
HCT-116 CHEMBL394	IC50	7.1	7.1	79.0	1
Serine/threonine-protein kinase N2 CHEMBL3032	Kd	6.85	6.85	141.0	1
DU-145 CHEMBL613508	IC50	6.85	6.85	140.0	1
Ferrochelatase, mitochondrial CHEMBL3879831	Kd	6.61	6.61	243.0	1
Cyclin-dependent kinase 2 CHEMBL301	Kd	6.61	6.61	243.0	1
Interleukin-1 receptor-associated kinase 3 CHEMBL5081	Kd	6.54	6.54	286.0	1
Serine/threonine-protein kinase 3 CHEMBL4708	Kd	6.51	6.51	311.0	1
General transcription and DNA repair factor IIH helicase subunit XPD CHEMBL4105743	Kd	6.5	6.5	319.0	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	Kd	6.38	6.38	418.0	1
Glycogen synthase kinase-3 beta CHEMBL262	Kd	6.35	6.35	447.0	1
Cyclin-dependent kinase 7 CHEMBL3055	Kd	6.33	6.33	473.0	1
Serine/threonine-protein kinase D2 CHEMBL4900	Kd	6.32	6.32	474.0	1
Serine/threonine-protein kinase D3 CHEMBL2595	Kd	6.25	6.25	557.0	1
Glycogen synthase kinase-3 alpha CHEMBL2850	Kd	6.24	6.24	579.0	1
Mitogen-activated protein kinase kinase kinase kinase 3 CHEMBL5432	Kd	6.07	6.07	850.0	1
Protein kinase C alpha type CHEMBL299	Kd	6.05	6.05	885.0	1
Cyclin-dependent kinase 5 CHEMBL4036	Kd	6.03	6.03	930.0	1
Cytochrome P450 2D6 CHEMBL289	IC50	6.02	6.02	950.0	2
Protein kinase C delta type CHEMBL2996	Kd	6.0	6.0	996.0	1
Mitogen-activated protein kinase 15 CHEMBL5198	Kd	5.97	5.97	1073.0	1
Serine/threonine-protein kinase TAO2 CHEMBL1075195	Kd	5.97	5.97	1070.0	1
Serine/threonine-protein kinase SIK3 CHEMBL6149	Kd	5.89	5.89	1300.0	1
Mitogen-activated protein kinase kinase kinase kinase 2 CHEMBL5330	Kd	5.87	5.87	1364.0	1
Mitogen-activated protein kinase 8 CHEMBL2276	Kd	5.84	5.84	1457.0	1
Cyclin-dependent kinase 6 CHEMBL2508	Kd	5.8	5.8	1597.0	1
Serine/threonine-protein kinase N1 CHEMBL3384	Kd	5.77	5.77	1689.0	1
Tyrosine-protein kinase Fer CHEMBL3982	Kd	5.77	5.77	1695.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	752.0	ng.hr.mL-1	Mus musculus
AUC	2523.0	ng.hr.mL-1	Mus musculus
CL	110.0	mL.min-1.kg-1	Mus musculus
Cmax	2762.64	nM	Mus musculus
F	24.0	%	Mus musculus
F	4.0	%	Rattus norvegicus
F	37.0	%	Canis lupus familiaris
T1/2	0.75	hr	Homo sapiens
T1/2	0.2	hr	Mus musculus
T1/2	0.1833	hr	Rattus norvegicus
T1/2	0.55	hr	Canis lupus familiaris
T1/2	4.6	hr	Mus musculus
T1/2	6.1	hr	Mus musculus
T1/2	0.75	hr	Homo sapiens
T1/2	0.2	hr	Mus musculus
Tmax	0.5	hr	Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Cyclin-dependent kinase 9	Kd	=	1.0	nM	9.0	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Cyclin-dependent kinase 9	IC50	=	2.0	nM	8.7	Inhibition of human CDK9	32866383
CDK9/Cyclin K	IC50	=	3.0	nM	8.52	Inhibition of human recombinant full length His-tagged CDK9/cyclin K expressed i...	30543440
Cyclin-dependent kinase 2	IC50	=	3.0	nM	8.52	Inhibition of CDK2 (unknown origin)	27171036
Cyclin-dependent kinase 9	IC50	=	3.0	nM	8.52	Inhibition of human GST-tagged CDK9	27171036
CDK3/Cyclin E	IC50	=	3.0	nM	8.52	Inhibition of recombinant human full length C-terminal His6-tagged CDK3/N-termin...	27171036
Cyclin-dependent kinase 5	IC50	=	3.0	nM	8.52	Inhibition of human GST-tagged CDK5	27171036
Cyclin-dependent kinase 1	IC50	=	3.0	nM	8.52	Inhibition of CDK1 (unknown origin)	27171036
CDK7/Cyclin H/MNAT1	IC50	=	3.0	nM	8.52	Inhibition of recombinant human full length C-terminal His6-tagged CDK7/cyclin H...	27171036
Cyclin-dependent kinase 5	IC50	=	4.0	nM	8.4	Inhibition of human CDK5	32866383
Cyclin-dependent kinase 5/CDK5 activator 1	IC50	=	4.0	nM	8.4	Inhibition of human recombinant full-length GST/His-tagged CDK5/p25 expressed in...	30543440
Cyclin-dependent kinase 2/cyclin E1	IC50	=	5.0	nM	8.3	Inhibition of human recombinant GST-tagged CDK2/cyclin E1	30543440
Cyclin-dependent kinase 2	IC50	=	5.0	nM	8.3	Inhibition of human CDK2	32866383
CDK3/Cyclin E	IC50	=	8.0	nM	8.1	Inhibition of recombinant human full-length C-terminal His6-tagged CDK3/full-len...	30543440
CDK3/Cyclin E	IC50	=	8.0	nM	8.1	Inhibition of C-terminal His6-tagged human CDK3/N-terminal GST-tagged human cycl...	32866383
Cyclin-dependent kinase 1/cyclin B1	IC50	=	9.0	nM	8.05	Inhibition of human recombinant full-length His-tagged CDK1/cyclin B1 expressed ...	30543440
Cyclin-dependent kinase 1	IC50	=	9.0	nM	8.05	Inhibition of human CDK1	32866383
Cyclin-dependent kinase 2/cyclin A	IC50	=	13.0	nM	7.89	Inhibition of recombinant Cdk2/cyclin A using RbING as substrate after 2 hrs by ...	22148278
CDK2/Cyclin A2	IC50	=	13.0	nM	7.89	Inhibition of CDK2/Cyclin A (unknown origin)	35485642
Cyclin-dependent kinase 2	IC50	=	13.0	nM	7.89	Inhibition of CDK2 (unknown origin) by LANCE ULight TR-FRET assay	38389874

Literature References

PubMed	DOI	Target Context	# Activities
22148278	10.1021/jm201112g	Mus musculus	9
22148278	10.1021/jm201112g	Cyclin-dependent kinase 2	5
29191878	10.1126/science.aan4368	Unchecked	4
22148278	10.1021/jm201112g	HCT-116	4
22148278	10.1021/jm201112g	Ramos	4
-	10.6019/CHEMBL4495565	SARS-CoV-2	4
22148278	10.1021/jm201112g	Plasma	3
22148278	10.1021/jm201112g	Caco-2	3
38389874	10.1039/d3md00457k	ADMET	3
22148278	10.1021/jm201112g	Liver microsomes	2
22148278	10.1021/jm201112g	Liver	2
-	10.6019/CHEMBL4495564	Replicase polyprotein 1ab	2
-	10.6019/CHEMBL4808148	Histone deacetylase 6	2
37002872	10.1021/acs.jmedchem.3c00072	Mitogen-activated protein kinase 7	2
22148278	10.1021/jm201112g	DU-145	1
38389874	10.1039/d3md00457k	Cyclin-dependent kinase 2	1
22148278	10.1021/jm201112g	Cytochrome P450 3A4	1
22148278	10.1021/jm201112g	HL-60	1
22148278	10.1021/jm201112g	No relevant target	1
22148278	10.1021/jm201112g	Tyrosine-protein kinase JAK2	1

Data from ChEMBL 36 via Core Engine