Compound Detail

CHEMBL3545085

XL-228

Phase I

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Phase I

CC(C)c1cc(CNc2nc(Nc3cc(C4CC4)[nH]n3)cc(N3CCN(C)CC3)n2)on1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL3545085
Name	XL-228
Phase	Phase I
Structure Type	MOL
InChI Key	ALKJNCZNEOTEMP-UHFFFAOYSA-N

Known Names

Exel-2280 Xl-228 XL228

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

437.6

MW (Da)

3.30

ALogP

HBA

HBD

111.0

PSA (Å²)

0.49

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Achiral

Extended Properties

Molecular Formula	C22H31N9O
MW	437.55
Aromatic Rings	3
Heavy Atoms	32
NP-Likeness	-1.72

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Tyrosine-protein kinase ABL inhibitor	INHIBITOR	Tyrosine-protein kinase ABL1	✓	✓
Insulin-like growth factor I receptor inhibitor	INHIBITOR	Insulin-like growth factor 1 receptor	✓	✓
SRC inhibitor	INHIBITOR	SRC	✓	✓

Indications

Leukemia, Myelogenous, Chronic, BCR-ABL Positive Lymphoma Neoplasms Precursor Cell Lymphoblastic Leukemia-Lymphoma

Activity Summary

Kd 82 meas. best 8.52

IC50 7 meas. best 8.51

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Aurora kinase A CHEMBL4722	Kd	8.52	8.52	3.0	1
Breakpoint cluster region protein CHEMBL5146	Kd	8.52	8.52	3.0	1
Serine/threonine-protein kinase PLK4 CHEMBL3788	Kd	8.52	8.52	3.0	1
Non-receptor tyrosine-protein kinase TNK1 CHEMBL5334	Kd	8.52	8.52	3.0	1
Aurora kinase A CHEMBL4722	IC50	8.51	8.51	3.1	1
Aurora kinase B CHEMBL2185	Kd	8.4	8.4	4.0	1
Tyrosine-protein kinase ABL1 CHEMBL1862	IC50	8.3	8.075	5.0	2
Cyclin-dependent kinase 17 CHEMBL5790	Kd	8.3	8.3	5.0	1
Ephrin type-A receptor 1 CHEMBL5810	Kd	8.3	8.3	5.0	1
Activin receptor type-1 CHEMBL5903	Kd	8.3	8.3	5.0	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	Kd	8.3	8.3	5.0	1
High affinity nerve growth factor receptor CHEMBL2815	Kd	8.22	8.22	6.0	1
Tyrosine-protein kinase ABL2 CHEMBL4014	Kd	8.1	8.1	8.0	1
Proto-oncogene tyrosine-protein kinase receptor Ret CHEMBL2041	Kd	8.05	8.05	9.0	1
Fibroblast growth factor receptor 1 CHEMBL3650	Kd	8.05	8.05	9.0	1
Serine/threonine-protein kinase N1 CHEMBL3384	Kd	7.96	7.96	11.0	1
BMP-2-inducible protein kinase CHEMBL4522	Kd	7.85	7.85	14.0	1
Mitogen-activated protein kinase kinase kinase kinase 1 CHEMBL5749	Kd	7.82	7.82	15.0	1
Ephrin type-A receptor 7 CHEMBL4602	Kd	7.77	7.77	17.0	1
Focal adhesion kinase 1 CHEMBL2695	Kd	7.66	7.66	22.0	1
Tyrosine-protein kinase Fyn CHEMBL1841	Kd	7.64	7.64	23.0	1
Ephrin type-B receptor 6 CHEMBL5836	Kd	7.58	7.58	26.0	1
Ephrin type-A receptor 2 CHEMBL2068	Kd	7.5	7.5	32.0	1
K562 CHEMBL385	IC50	7.48	7.425	33.0	2
Tyrosine-protein kinase Tec CHEMBL4246	Kd	7.35	7.35	45.0	1
Insulin-like growth factor 1 receptor CHEMBL1957	IC50	7.3	7.3	50.0	1
Tyrosine-protein kinase ABL1 CHEMBL1862	Kd	7.12	7.12	75.0	1
Activated CDC42 kinase 1 CHEMBL4599	Kd	7.12	7.12	76.0	1
Interleukin-1 receptor-associated kinase 3 CHEMBL5081	Kd	7.1	7.1	80.0	1
Ephrin type-A receptor 5 CHEMBL3987	Kd	7.09	7.09	81.0	1
Tyrosine-protein kinase Fer CHEMBL3982	Kd	6.98	6.98	105.0	1
Protein-tyrosine kinase 2-beta CHEMBL5469	Kd	6.93	6.93	118.0	1
MAP/microtubule affinity-regulating kinase 3 CHEMBL5600	Kd	6.88	6.88	133.0	1
STE20-like serine/threonine-protein kinase CHEMBL4202	Kd	6.86	6.86	138.0	1
AP2-associated protein kinase 1 CHEMBL3830	Kd	6.86	6.86	138.0	1
Insulin receptor CHEMBL1981	Kd	6.84	6.84	144.0	1
Tyrosine-protein kinase Lck CHEMBL258	Kd	6.78	6.78	166.0	1
Ephrin type-A receptor 4 CHEMBL3988	Kd	6.78	6.78	167.0	1
Tyrosine-protein kinase Yes CHEMBL2073	Kd	6.77	6.77	171.0	1
TRAF2 and NCK-interacting protein kinase CHEMBL4527	Kd	6.74	6.74	184.0	1
Serine/threonine-protein kinase MARK2 CHEMBL3831	Kd	6.71	6.71	196.0	1
Uncharacterized protein FLJ45252 CHEMBL4105933	Kd	6.69	6.69	204.0	1
Bone morphogenetic protein receptor type-1A CHEMBL5275	Kd	6.69	6.69	203.0	1
Bone morphogenetic protein receptor type-1B CHEMBL5476	Kd	6.67	6.67	212.0	1
Epithelial discoidin domain-containing receptor 1 CHEMBL5319	Kd	6.66	6.66	221.0	1
Serine/threonine-protein kinase 4 CHEMBL4598	Kd	6.64	6.64	229.0	1
TGF-beta receptor type-1 CHEMBL4439	Kd	6.64	6.64	231.0	1
Ephrin type-B receptor 4 CHEMBL5147	Kd	6.54	6.54	292.0	1
Mitogen-activated protein kinase kinase kinase kinase 2 CHEMBL5330	Kd	6.45	6.45	352.0	1
5'-AMP-activated protein kinase catalytic subunit alpha-1 CHEMBL4045	Kd	6.42	6.42	380.0	1

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Non-receptor tyrosine-protein kinase TNK1	Kd	=	3.0	nM	8.52	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Serine/threonine-protein kinase PLK4	Kd	=	3.0	nM	8.52	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Breakpoint cluster region protein	Kd	=	3.0	nM	8.52	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Aurora kinase A	Kd	=	3.0	nM	8.52	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Aurora kinase A	IC50	=	3.1	nM	8.51	Inhibition of Aurora A (unknown origin)	35551036
Aurora kinase B	Kd	=	4.0	nM	8.4	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Activin receptor type-1	Kd	=	5.0	nM	8.3	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Cyclin-dependent kinase 17	Kd	=	5.0	nM	8.3	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Ephrin type-A receptor 1	Kd	=	5.0	nM	8.3	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Receptor-type tyrosine-protein kinase FLT3	Kd	=	5.0	nM	8.3	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Tyrosine-protein kinase ABL1	IC50	=	5.0	nM	8.3	Inhibition of wild type Abl (unknown origin)	35551036
High affinity nerve growth factor receptor	Kd	=	6.0	nM	8.22	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Tyrosine-protein kinase ABL2	Kd	=	8.0	nM	8.1	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Proto-oncogene tyrosine-protein kinase receptor Ret	Kd	=	9.0	nM	8.05	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Fibroblast growth factor receptor 1	Kd	=	9.0	nM	8.05	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Serine/threonine-protein kinase N1	Kd	=	11.0	nM	7.96	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Tyrosine-protein kinase ABL1	IC50	=	14.0	nM	7.85	Inhibition of Abl T315I mutant (unknown origin)	35551036
BMP-2-inducible protein kinase	Kd	=	14.0	nM	7.85	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Mitogen-activated protein kinase kinase kinase kinase 1	Kd	=	15.0	nM	7.82	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Ephrin type-A receptor 7	Kd	=	17.0	nM	7.77	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878

Literature References

PubMed	DOI	Target Context	# Activities
29191878	10.1126/science.aan4368	Unchecked	5
-	10.6019/CHEMBL4495564	Replicase polyprotein 1ab	5
-	10.6019/CHEMBL4495565	SARS-CoV-2	4
35551036	10.1016/j.ejmech.2022.114442	K562	2
-	10.6019/CHEMBL4808148	Histone deacetylase 6	2
35551036	10.1016/j.ejmech.2022.114442	Tyrosine-protein kinase ABL1	2
29191878	10.1126/science.aan4368	Activin receptor type-1	1
29191878	10.1126/science.aan4368	RAC-beta serine/threonine-protein kinase	1
29191878	10.1126/science.aan4368	RAC-alpha serine/threonine-protein kinase	1
-	10.6019/EOS300108	HepG2	1
29191878	10.1126/science.aan4368	Atypical kinase COQ8A, mitochondrial	1
29191878	10.1126/science.aan4368	AarF domain-containing protein kinase 1	1
29191878	10.1126/science.aan4368	Activin receptor type-2B	1
29191878	10.1126/science.aan4368	Activin receptor type-1B	1
29191878	10.1126/science.aan4368	Actin-related protein 2	1
29191878	10.1126/science.aan4368	Long-chain-fatty-acid--CoA ligase 5	1
29191878	10.1126/science.aan4368	Peroxisomal acyl-coenzyme A oxidase 1	1
29191878	10.1126/science.aan4368	Very long-chain specific acyl-CoA dehydrogenase, mitochondrial	1
29191878	10.1126/science.aan4368	Acyl-CoA dehydrogenase family member 11	1
29191878	10.1126/science.aan4368	Tyrosine-protein kinase ABL2	1

Data from ChEMBL 36 via Core Engine