Compound Detail

CHEMBL573339

PI-103

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Oc1cccc(-c2nc(N3CCOCC3)c3oc4ncccc4c3n2)c1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL573339
Name	PI-103
Phase	Preclinical
Structure Type	MOL
InChI Key	TUVCWJQQGGETHL-UHFFFAOYSA-N

Targets

271

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

348.4

MW (Da)

2.98

ALogP

HBA

HBD

84.5

PSA (Å²)

0.60

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Availability	Unknown
Chirality	Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula	C19H16N4O3
MW	348.36
Aromatic Rings	4
Heavy Atoms	26
NP-Likeness	-1.09

Activity Summary

IC50 207 meas. best 9.22

Kd 58 meas. best 8.89

Ki 6 meas. best 6.1

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
HUVEC CHEMBL613979	IC50	9.22	9.22	0.6	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform CHEMBL4005	Kd	8.89	8.7233	1.3	12
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform CHEMBL3145	Kd	8.77	8.77	1.7	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform CHEMBL4005	IC50	8.75	7.9971	1.8	41
PI3-kinase p110-alpha/p85-alpha CHEMBL2111367	IC50	8.7	8.252	2.0	5
DNA-dependent protein kinase catalytic subunit CHEMBL3142	IC50	8.7	7.9275	2.0	4
TT CHEMBL2366083	IC50	8.66	8.66	2.2	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform CHEMBL3267	IC50	8.6	7.4332	2.5	19
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform CHEMBL3145	IC50	8.52	8.0558	3.0	19
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform CHEMBL3130	IC50	8.52	8.133	3.0	20
Phosphatidylinositol 3-kinase catalytic subunit type 3 CHEMBL1075165	IC50	8.4	8.4	4.0	1
Serine/threonine-protein kinase mTOR CHEMBL2842	IC50	8.28	7.5824	5.3	21
Unchecked CHEMBL612545	IC50	8.13	7.1178	7.4	18
PI3-kinase p110-delta/p85-alpha CHEMBL2111432	IC50	8.02	7.9433	9.6	3
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta CHEMBL5554	Kd	8.0	8.0	10.0	1
Serine/threonine-protein kinase mTOR CHEMBL2842	Kd	7.92	7.92	12.0	1
PI3K p110 beta/p85 alpha CHEMBL3038510	IC50	7.92	7.92	12.0	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform CHEMBL3267	Kd	7.8	7.8	16.0	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform CHEMBL3130	Kd	7.77	7.77	17.0	1
mTORC1 CHEMBL4296661	IC50	7.7	7.7	20.0	3
Lung cancer cell line CHEMBL614103	IC50	7.7	7.7	20.0	1
Melanoma tumor cell line CHEMBL612704	IC50	7.7	7.7	20.0	1
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta CHEMBL5554	IC50	7.58	7.475	26.0	2
Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma CHEMBL1163120	Kd	7.39	7.39	41.0	1
MV4-11 CHEMBL613835	IC50	7.27	7.27	54.0	1
HL-60 CHEMBL383	IC50	7.18	7.115	65.6	2
mTORC2 CHEMBL4523999	IC50	7.08	7.08	83.0	1
KG-1 CHEMBL612264	IC50	7.06	7.06	88.0	1
CWR22R CHEMBL612657	IC50	7.0	7.0	100.0	1
SK-OV-3 CHEMBL614925	IC50	6.96	6.96	110.0	1
MDA-MB-231 CHEMBL400	IC50	6.85	5.59	140.0	3
HeLa CHEMBL399	IC50	6.8	6.29	160.0	3
PC-3 CHEMBL390	IC50	6.77	5.9075	170.0	4
A549 CHEMBL392	IC50	6.75	6.075	180.0	2
Homeodomain-interacting protein kinase 2 CHEMBL4576	Kd	6.54	6.54	290.0	1
Homeodomain-interacting protein kinase 3 CHEMBL4577	Kd	6.51	6.51	310.0	1
Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma CHEMBL1770034	Kd	6.21	6.21	620.0	1
Serine/threonine-protein kinase RIO2 CHEMBL6000	Kd	6.11	6.11	770.0	1
Death-associated protein kinase 3 CHEMBL2468	Ki	6.1	6.1	794.3	1
Dual specificity protein kinase CLK4 CHEMBL4203	Ki	6.1	6.1	794.3	1
Caco-2 CHEMBL614058	IC50	6.1	5.95	800.0	3
Death-associated protein kinase 3 CHEMBL2468	Kd	6.08	6.08	840.0	2
Mitogen-activated protein kinase kinase kinase 19 CHEMBL6191	Kd	6.03	6.03	930.0	1
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha CHEMBL1075102	IC50	6.0	6.0	1000.0	1
HCT-116 CHEMBL394	IC50	6.0	5.6433	1000.0	3
SW-620 CHEMBL612262	IC50	5.97	5.97	1070.0	1
HT-29 CHEMBL384	IC50	5.88	5.88	1310.0	1
Myosin light chain kinase, smooth muscle CHEMBL2428	Kd	5.82	5.82	1500.0	2
Huh-7 CHEMBL614039	IC50	5.82	5.52	1500.0	2
ADMET CHEMBL612558	IC50	5.82	5.82	1500.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	9.7	ng.hr.mL-1	Mus musculus
AUC	-	ng.hr.mL-1	Mus musculus
AUC	217.48	ng.hr.mL-1	Mus musculus
AUC	279.21	ng.hr.mL-1	Mus musculus
AUC	157.81	ng.hr.mL-1	Mus musculus
AUC	141.54	ng.hr.mL-1	Mus musculus
AUC	7127.45	ng.hr.mL-1	Mus musculus
CL	0.19	L/hr	Mus musculus
CL	0.26	L/hr	Mus musculus
CL	0.27	L/hr	Mus musculus
CL	0.12	L/hr	Mus musculus
Cmax	4.019	nM	Mus musculus
Cmax	-	nM	Mus musculus
Cmax	4168.8	nM	Mus musculus
Cmax	801.5	nM	Mus musculus
Cmax	2022.6	nM	Mus musculus
Cmax	1361.9	nM	Mus musculus
Cmax	6680.0	nM	Mus musculus
T1/2	0.1183	hr	Mus musculus
T1/2	2.0	hr	Mus musculus
t1/2	-	-	Mus musculus
T1/2	0.1183	hr	Mus musculus
T1/2	0.7	hr	Mus musculus
T1/2	4.2	hr	Mus musculus
T1/2	0.9	hr	Mus musculus
T1/2	1.3	hr	Mus musculus
T1/2	0.12	hr	Mus musculus
Tmax	3.0	hr	Mus musculus
Tmax	-	-	Mus musculus
Tmax	-	hr	Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
HUVEC	IC50	=	0.6	nM	9.22	Antiangiogenic activity against HUVEC after 24 hrs by calcein AM staining-based ...	18849971
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Kd	=	1.3	nM	8.89	Binding constant for PIK3CA(C420R) kinase domain	22037378
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Kd	=	1.4	nM	8.85	Binding constant for PIK3CA(E542K) kinase domain	22037378
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Kd	=	1.5	nM	8.82	Binding constant for PIK3CA kinase domain	18183025
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Kd	=	1.5	nM	8.82	Binding constant for PIK3CA(E545K) kinase domain	18183025
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Kd	=	1.5	nM	8.82	Binding constant for PIK3CA kinase domain	22037378
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Kd	=	1.5	nM	8.82	Binding constant for PIK3CA(E545A) kinase domain	22037378
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Kd	=	1.5	nM	8.82	Binding constant for PIK3CA(E545K) kinase domain	22037378
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Kd	=	1.5	nM	8.82	Binding constant for PIK3CA(Q546K) kinase domain	22037378
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	Kd	=	1.7	nM	8.77	Binding constant for PIK3CB kinase domain	22037378
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	1.76	nM	8.75	Inhibition of PI3Kalpha (unknown origin)	28259529
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	2.0	nM	8.7	Inhibition of P13Kalpha (unknown origin) in the presence of ATP by scintillation...	36462440
DNA-dependent protein kinase catalytic subunit	IC50	=	2.0	nM	8.7	Inhibition of human DNA-PK by non-radiometric ADP-Glo assay	25589915
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	2.0	nM	8.7	Inhibition of human recombinant PI3K alpha by scintillation proximity radiometri...	26731167
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	2.0	nM	8.7	Inhibition of human recombinant PI3Kalpha in the presence of ATP by scintillatio...	17575152
PI3-kinase p110-alpha/p85-alpha	IC50	=	2.0	nM	8.7	Competitive inhibition of human PI3K p110alpha/p85alpha using PIP2 as substrate ...	28571824
PI3-kinase p110-alpha/p85-alpha	IC50	=	2.0	nM	8.7	Inhibition of human PI3K p110alpha/p85alpha using PIP2 as substrate incubated fo...	33214824
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	2.0	nM	8.7	Inhibition of PI3Kalpha (unknown origin) using biotin-PIP3 as substrate preincub...	38183777
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	2.0	nM	8.7	Inhibition of GST-tagged Ptdlns3p P110alpha (unknown origin) expressed in baculo...	18188180
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	2.0	nM	8.7	Inhibition of human recombinant PI3K p110-alpha incubated for 120 mins in presen...	37669595

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL4689842	Fibroblast	345
-	10.6019/CHEMBL4689842	HEK-293T	344
-	10.6019/CHEMBL4689842	U2OS	343
17575152	10.1158/0008-5472.can-06-4615	ADMET	34
17575152	10.1158/0008-5472.can-06-4615	Unchecked	18
32527558	10.1016/j.bmcl.2020.127258	ADMET	18
17575152	10.1158/0008-5472.can-06-4615	OVCAR-3	18
17575152	10.1158/0008-5472.can-06-4615	U-87 MG	15
22037378	10.1038/nbt.1990	Tyrosine-protein kinase ABL1	15
22037378	10.1038/nbt.1990	Epidermal growth factor receptor	12
17575152	10.1158/0008-5472.can-06-4615	HCT-116	12
17575152	10.1158/0008-5472.can-06-4615	MDA-MB-468	10
17575152	10.1158/0008-5472.can-06-4615	PC-3	10
18183025	10.1038/nbt1358	Epidermal growth factor receptor	10
22037378	10.1038/nbt.1990	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	10
32527558	10.1016/j.bmcl.2020.127258	No relevant target	10
26254279	10.18632/oncotarget.4214	Unchecked	9
17575152	10.1158/0008-5472.can-06-4615	MDA-MB-435	8
19402821	10.1042/bj20090489	Unchecked	8
22037378	10.1038/nbt.1990	Mast/stem cell growth factor receptor Kit	8

Data from ChEMBL 36 via Core Engine