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Compound Detail

CHEMBL521851

PICTILISIB
🧪 Phase II
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🧪 Phase II
CS(=O)(=O)N1CCN(Cc2cc3nc(-c4cccc5[nH]ncc45)nc(N4CCOCC4)c3s2)CC1

Basic Information

ChEMBL ID CHEMBL521851
Name PICTILISIB
Phase Phase II
Structure Type MOL
InChI Key LHNIIDJUOCFXAP-UHFFFAOYSA-N

Known Names

CDC-0941 GDC 0941 GDC-0941 Pictilisib Pictrelisib Rg-7321
553
Targets
840
Activities
4
Assay Types
9
PK Parameters
20
Publications
6
Known Names
5
Indications
1
Mechanisms

Molecular Properties

513.6
MW (Da)
2.15
ALogP
9
HBA
1
HBD
107.5
PSA (Ų)
0.43
QED
1
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral

Flags

Natural Product Chemical Probe
USAN Stem -lisib
USAN Year 2011

Extended Properties

Molecular Formula C23H27N7O3S2
MW 513.65
Aromatic Rings 4
Heavy Atoms 35
NP-Likeness -2.11

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
PI3-kinase class I inhibitor INHIBITOR PI3-kinase class I

Indications

Breast Neoplasms Carcinoma, Non-Small-Cell Lung Lymphoma, Non-Hodgkin Neoplasms Neoplasms

Activity Summary

IC50 739 meas. best 10.0
Kd 76 meas. best 9.12
Ki 19 meas. best 8.85
EC50 6 meas. best 6.77

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
CHEMBL4005
IC50 10.0 8.2056 0.1 32
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
CHEMBL4005
Kd 9.12 8.7433 0.8 12
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
CHEMBL3267
Ki 8.85 8.3467 1.4 3
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
CHEMBL3130
Ki 8.81 7.9 1.5 3
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
CHEMBL3145
Kd 8.68 8.3867 2.1 3
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
CHEMBL4005
Ki 8.59 8.39 2.6 3
Unchecked
CHEMBL612545
Ki 8.59 8.59 2.6 1
Serine/threonine-protein kinase mTOR
CHEMBL2842
IC50 8.52 6.4618 3.0 11
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
CHEMBL3130
IC50 8.52 8.1472 3.0 18
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
CHEMBL3145
IC50 8.52 7.3756 3.0 16
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
CHEMBL3267
IC50 8.52 7.0912 3.0 17
Unchecked
CHEMBL612545
IC50 8.52 6.38 3.0 11
PI3-kinase p110-delta/p85-alpha
CHEMBL2111432
IC50 8.48 7.56 3.3 3
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
CHEMBL3130
Kd 8.48 8.42 3.3 3
PI3-kinase p110-alpha/p85-alpha
CHEMBL2111367
IC50 8.32 7.796 4.8 5
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
CHEMBL3267
Kd 8.11 7.8467 7.7 3
RAC-alpha serine/threonine-protein kinase
CHEMBL4282
IC50 7.55 7.44 28.0 3
SU-DHL-6
CHEMBL4296496
IC50 7.52 7.52 30.0 1
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta
CHEMBL5554
Kd 7.4 7.23 40.0 3
Serine/threonine-protein kinase mTOR
CHEMBL2842
Kd 7.32 7.1133 48.0 3
ES5
CHEMBL2366312
IC50 7.3 7.3 50.2 1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
CHEMBL5169092
IC50 7.28 7.28 52.0 1
PI3K p110 beta/p85 alpha
CHEMBL3038510
IC50 7.27 7.12 54.0 2
MCF7
CHEMBL387
IC50 7.16 6.2417 70.0 6
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
CHEMBL3145
Ki 7.15 7.15 70.2 1
Phosphatidylinositol 3-kinase regulatory subunit beta
CHEMBL4437
Ki 7.15 7.15 70.2 1
MM1.S
CHEMBL4296471
IC50 7.0 7.0 100.0 1
HH
CHEMBL2366310
IC50 6.95 6.95 111.1 1
MHH-PREB-1
CHEMBL2366127
IC50 6.94 6.94 114.3 1
PI3-kinase subunit gamma/Phosphoinositide 3-kinase regulatory subunit 5
CHEMBL3430881
IC50 6.93 6.93 117.0 1
NCI-H1770
CHEMBL2366171
IC50 6.91 6.91 123.9 1
A2780
CHEMBL614004
IC50 6.85 6.105 140.0 2
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
CHEMBL3608198
IC50 6.84 6.84 146.0 1
Unchecked
CHEMBL612545
EC50 6.77 6.77 170.0 1
MOLT-4
CHEMBL614177
IC50 6.75 6.48 180.0 2
NON-PROTEIN TARGET
CHEMBL3879801
IC50 6.7 6.1831 200.0 13
HuO9
CHEMBL1075476
IC50 6.69 6.69 206.0 1
HAL-01
CHEMBL2366142
IC50 6.68 6.68 206.7 1
HGC-27
CHEMBL1075463
IC50 6.67 6.67 212.6 1
NOS-1
CHEMBL2366141
IC50 6.67 6.67 211.8 1
NB69
CHEMBL1075510
IC50 6.61 6.61 245.3 1
RS4-11
CHEMBL2366159
IC50 6.58 6.58 261.8 1
NCI-H1975
CHEMBL614348
IC50 6.57 6.1133 270.0 3
PC-3
CHEMBL390
IC50 6.55 6.2 280.0 6
MDA-MB-231
CHEMBL400
IC50 6.55 5.5025 280.0 4
DOK
CHEMBL1075435
IC50 6.52 6.52 301.7 1
NCI-H1623
CHEMBL1075517
IC50 6.52 6.52 304.1 1
Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma
CHEMBL1163120
Kd 6.52 6.52 300.0 1
YH-13
CHEMBL2366164
IC50 6.52 6.52 304.3 1
LB2241-RCC
CHEMBL2366330
IC50 6.52 6.52 303.8 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 41246.09 ng.hr.mL-1 Mus musculus
CL 11.9 mL.min-1.kg-1 Canis lupus familiaris
CL 14.79 mL.min-1.g-1 Homo sapiens
CL 33.11 uL.min-1.(10^6cells)-1 Rattus norvegicus
F 77.0 % Mus musculus
F 30.0 % Rattus norvegicus
F 20.0 % Macaca mulatta
F 71.0 % Canis lupus familiaris
T1/2 3.5 hr Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 0.1 nM 10.0 Inhibition of PI3Kalpha (unknown origin) 33077264
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Kd = 0.76 nM 9.12 Binding affinity to human PI3Kalpha (R108 to N1068 residues) expressed in mammal... 28829592
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Kd = 0.76 nM 9.12 Affinity Biochemical interaction (ScanMax technology (DiscoverX)) EUB0000049b PI... -
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Kd = 0.86 nM 9.07 Binding constant for PIK3CA(E545A) kinase domain 22037378
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Kd = 1.1 nM 8.96 Binding constant for PIK3CA kinase domain 22037378
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Kd = 1.2 nM 8.92 Binding constant for PIK3CA(E545K) kinase domain 22037378
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Ki = 1.4 nM 8.85 Inhibition of GST-fused human recombinant PI3Kgamma expressed in baculovirus inf... 23540645
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Kd = 1.5 nM 8.82 Binding constant for PIK3CA(C420R) kinase domain 22037378
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Kd = 1.5 nM 8.82 Binding constant for PIK3CA(E542K) kinase domain 22037378
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Ki = 1.54 nM 8.81 p110alpha (Alpha) PI3K Binding Assay: PI3K Binding assays are intended for deter... -
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Ki = 1.54 nM 8.81 Biochemical Inhibition Assay: The biochemical inhibition of four PI3K isoforms b... -
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Kd = 1.7 nM 8.77 Binding constant for PIK3CA(Q546K) kinase domain 22037378
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Kd = 2.1 nM 8.68 Binding affinity to human PI3Kbeta (P118 to S1070 residues) expressed in mammali... 28829592
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Kd = 2.1 nM 8.68 Affinity Biochemical interaction (ScanMax technology (DiscoverX)) EUB0000049b PI... -
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Ki = 2.56 nM 8.59 Biochemical Inhibition Assay: The biochemical inhibition of four PI3K isoforms b... -
Unchecked Ki = 2.56 nM 8.59 p110alpha (Alpha) PI3K Binding Assay: PI3K Binding assays are intended for deter... -
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Ki = 2.6 nM 8.59 Inhibition of GST-fused human recombinant PI3Kalpha expressed in baculovirus inf... 23540645
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 3.0 nM 8.52 Inhibition of p110 alpha (unknown origin) 20729870
Serine/threonine-protein kinase mTOR IC50 = 3.0 nM 8.52 Inhibition of mTOR (unknown origin) 31581005
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform IC50 = 3.0 nM 8.52 Inhibition of p110 delta (unknown origin) 20729870

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL4689842 Fibroblast 261
- 10.6019/CHEMBL4689842 U2OS 261
- 10.6019/CHEMBL4689842 HEK-293T 260
22084396 10.1158/0008-5472.can-11-1515 A2058 26
22084396 10.1158/0008-5472.can-11-1515 Unchecked 23
22037378 10.1038/nbt.1990 Tyrosine-protein kinase ABL1 15
25177796 10.1042/bj20140889 Unchecked 13
22037378 10.1038/nbt.1990 Epidermal growth factor receptor 12
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
22037378 10.1038/nbt.1990 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 10
26254279 10.18632/oncotarget.4214 Unchecked 9
30359003 10.1021/acs.jmedchem.8b01262 Unchecked 8
22084396 10.1158/0008-5472.can-11-1515 888-mel 8
22037378 10.1038/nbt.1990 Mast/stem cell growth factor receptor Kit 8
22037378 10.1038/nbt.1990 Receptor-type tyrosine-protein kinase FLT3 7
22084396 10.1158/0008-5472.can-11-1515 NCI-H2122 7
32184963 10.1021/acsmedchemlett.9b00378 A549 6
22336246 10.1016/j.bmc.2012.01.017 NON-PROTEIN TARGET 6
- 10.6019/CHEMBL4495565 SARS-CoV-2 6

Data from ChEMBL 36 via Core Engine