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Compound Detail

CHEMBL3128043

PF-03758309
Phase I
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Phase I
Cc1nc(Nc2n[nH]c3c2CN(C(=O)N[C@H](CN(C)C)c2ccccc2)C3(C)C)c2sccc2n1
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL3128043
Name PF-03758309
Phase Phase I
Structure Type MOL
InChI Key AYCPARAPKDAOEN-LJQANCHMSA-N

Known Names

Pf-03758309 PF-3758309
196
Targets
320
Activities
3
Assay Types
6
PK Parameters
20
Publications
2
Known Names
1
Indications
1
Mechanisms

Molecular Properties

490.6
MW (Da)
4.53
ALogP
7
HBA
3
HBD
102.1
PSA (Ų)
0.37
QED
0
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer

Flags

Natural Product

Extended Properties

Molecular Formula C25H30N8OS
MW 490.64
Aromatic Rings 4
Heavy Atoms 35
NP-Likeness -1.37

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Serine/threonine-protein kinase PAK 4 inhibitor INHIBITOR Serine/threonine-protein kinase PAK 4 ✓ ✓

Indications

Neoplasms

Activity Summary

IC50 197 meas. best 9.68
Kd 93 meas. best 8.7
Ki 30 meas. best 8.52

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
MCF10
CHEMBL613878
 IC50 9.68 9.68 0.2 1
HCC70
CHEMBL1075461
 IC50 9.64 9.64 0.2 1
HCC1187
CHEMBL2366202
 IC50 9.62 9.62 0.2 1
HCT-116
CHEMBL394
 IC50 9.62 8.55 0.2 3
HCC1954
CHEMBL1075459
 IC50 9.48 9.48 0.3 1
Hs-578T
CHEMBL614645
 IC50 9.43 9.43 0.4 1
BT-549
CHEMBL614072
 IC50 9.39 9.39 0.4 1
ZR-75-1
CHEMBL614393
 IC50 9.31 9.31 0.5 1
HCC38
CHEMBL1075460
 IC50 9.28 9.28 0.5 1
NCI-H1581
CHEMBL1075516
 IC50 9.22 9.22 0.6 1
MDA-MB-468
CHEMBL614335
 IC50 9.2 9.2 0.6 1
HCC1419
CHEMBL1075455
 IC50 9.1 9.1 0.8 1
NON-PROTEIN TARGET
CHEMBL3879801
 IC50 9.1 9.1 0.8 1
MDA-MB-436
CHEMBL4296465
 IC50 9.1 9.1 0.8 1
Unchecked
CHEMBL612545
 IC50 9.08 7.3458 0.8 12
AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1
CHEMBL2111345
 IC50 9.0 8.2 1.0 2
T47D
CHEMBL614361
 IC50 9.0 9.0 1.0 1
NCI-H520
CHEMBL614099
 IC50 8.95 8.6 1.1 2
HCC1806
CHEMBL1075457
 IC50 8.92 8.92 1.2 1
Serine/threonine-protein kinase PAK 4
CHEMBL4482
 IC50 8.89 7.8893 1.3 15
NCI-H2087
CHEMBL1075532
 IC50 8.87 8.62 1.4 2
NCI-H526
CHEMBL2366102
 IC50 8.85 8.85 1.4 1
HCC1395
CHEMBL1075454
 IC50 8.8 8.8 1.6 1
BT-474
CHEMBL614529
 IC50 8.74 8.74 1.8 1
RKO
CHEMBL614879
 IC50 8.74 8.74 1.8 1
NCI-H1770
CHEMBL2366171
 IC50 8.73 8.73 1.8 1
NCI-H2347
CHEMBL1075538
 IC50 8.7 8.7 2.0 1
Ribosomal protein S6 kinase alpha-3
CHEMBL2345
 IC50 8.7 7.735 2.0 2
Ribosomal protein S6 kinase alpha-1
CHEMBL2553
 IC50 8.7 7.48 2.0 2
General transcription and DNA repair factor IIH helicase subunit XPD
CHEMBL4105743
 Kd 8.7 8.7 2.0 1
NCI-H82
CHEMBL2366077
 IC50 8.68 8.68 2.1 1
HCC827
CHEMBL4296422
 IC50 8.66 8.35 2.2 2
SW-403
CHEMBL6066749
 IC50 8.66 8.66 2.2 1
NCI-H1573
CHEMBL1075515
 IC50 8.62 8.14 2.4 2
CAMA-1
CHEMBL1075416
 IC50 8.57 8.57 2.7 1
Serine/threonine-protein kinase PAK 4
CHEMBL4482
 Kd 8.57 8.242 2.7 5
COLO 205
CHEMBL614561
 IC50 8.55 7.7 2.8 2
Serine/threonine-protein kinase Chk2
CHEMBL2527
 Ki 8.52 8.52 3.0 1
Cyclin-dependent kinase 7
CHEMBL3055
 Kd 8.52 8.52 3.0 1
Serine/threonine-protein kinase PAK 6
CHEMBL4311
 Kd 8.52 8.52 3.0 1
SK-MES-1
CHEMBL614923
 IC50 8.49 8.49 3.2 1
NCI-H23
CHEMBL614997
 IC50 8.46 8.03 3.5 2
NCI-H1666
CHEMBL1075520
 IC50 8.42 8.31 3.8 2
HCC4006
CHEMBL4523575
 IC50 8.42 8.42 3.8 1
Ribosomal protein S6 kinase alpha-6
CHEMBL4924
 Kd 8.4 8.4 4.0 1
NCI-H1734
CHEMBL1075523
 IC50 8.39 8.39 4.1 1
SW948
CHEMBL1075598
 IC50 8.37 8.37 4.3 1
HT-29
CHEMBL384
 IC50 8.37 8.37 4.3 1
NCI-H1703
CHEMBL1075522
 IC50 8.36 8.36 4.4 1
NCI-H1437
CHEMBL1075513
 IC50 8.32 8.32 4.8 1

Pharmacokinetic Data

Parameter Value Units Species
Cmax 10000.0 nM Mus musculus
Cmax 10000.0 nM Mus musculus
F 1.0 % Homo sapiens
Fu 0.163 - Mus musculus
T1/2 0.01889 hr Homo sapiens
T1/2 0.01889 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
MCF10 IC50 = 0.21 nM 9.68 Antiproliferative activity against human MCF10 cells assessed as inhibition of c... 20439741
HCC70 IC50 = 0.23 nM 9.64 Antiproliferative activity against human HCC70 cells assessed as inhibition of c... 20439741
HCT-116 IC50 = 0.24 nM 9.62 Inhibition of anchorage independent cell growth in human HCT-116 cells incubated... 20439741
HCC1187 IC50 = 0.24 nM 9.62 Antiproliferative activity against human HCC1187 cells assessed as inhibition of... 20439741
HCC1954 IC50 = 0.33 nM 9.48 Antiproliferative activity against human HCC1954 cells assessed as inhibition of... 20439741
Hs-578T IC50 = 0.37 nM 9.43 Antiproliferative activity against human Hs-578T cells assessed as inhibition of... 20439741
BT-549 IC50 = 0.41 nM 9.39 Antiproliferative activity against human BT-549 cells assessed as inhibition of ... 20439741
ZR-75-1 IC50 = 0.49 nM 9.31 Antiproliferative activity against human ZR-75-1 cells assessed as inhibition of... 20439741
HCC38 IC50 = 0.52 nM 9.28 Antiproliferative activity against human HCC38 cells assessed as inhibition of c... 20439741
NCI-H1581 IC50 = 0.6 nM 9.22 Antiproliferative activity against human NCI-H1581 cells assessed as inhibition ... 20439741
MDA-MB-468 IC50 = 0.63 nM 9.2 Antiproliferative activity against human MDA-MB-468 cells assessed as inhibition... 20439741
MDA-MB-436 IC50 = 0.79 nM 9.1 Antiproliferative activity against human MDA-MB-436 cells assessed as inhibition... 20439741
NON-PROTEIN TARGET IC50 = 0.79 nM 9.1 Cytotoxicity against human MDA-MB-436 cells assessed as reduction in cell viabil... 24432870
HCC1419 IC50 = 0.79 nM 9.1 Antiproliferative activity against human HCC1419 cells assessed as inhibition of... 20439741
Unchecked IC50 = 0.83 nM 9.08 Antiproliferative activity against human 184A1 cells assessed as inhibition of c... 20439741
AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 IC50 = 1.0 nM 9.0 Inhibition of human AMPK alpha1/beta1/gamma1 in presence of ATP 20439741
T47D IC50 = 0.99 nM 9.0 Antiproliferative activity against human T47D cells assessed as inhibition of ce... 20439741
NCI-H520 IC50 = 1.13 nM 8.95 Inhibition of anchorage independent cell growth in human NCI-H520 cells incubate... 20439741
HCC1806 IC50 = 1.2 nM 8.92 Antiproliferative activity against human HCC1806 cells assessed as inhibition of... 20439741
Serine/threonine-protein kinase PAK 4 IC50 = 1.3 nM 8.89 Inhibition of human PAK4 expressed in TR-293-KDG cells assessed as inhibition of... 33721669

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL4689842 Fibroblast 261
- 10.6019/CHEMBL4689842 U2OS 261
- 10.6019/CHEMBL4689842 HEK-293T 260
20439741 10.1073/pnas.0911863107 HCT-116 33
20439741 10.1073/pnas.0911863107 Unchecked 17
20439741 10.1073/pnas.0911863107 Protein kinase C beta type 10
20439741 10.1073/pnas.0911863107 Serine/threonine-protein kinase PAK 4 10
25415869 10.1021/jm501613q Serine/threonine-protein kinase PAK 4 7
- 10.6019/CHEMBL4495565 SARS-CoV-2 6
29191878 10.1126/science.aan4368 Unchecked 5
20439741 10.1073/pnas.0911863107 Receptor-type tyrosine-protein kinase FLT3 5
20439741 10.1073/pnas.0911863107 AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 5
20439741 10.1073/pnas.0911863107 Serine/threonine-protein kinase Chk2 5
20439741 10.1073/pnas.0911863107 Ribosomal protein S6 kinase alpha-2 5
20439741 10.1073/pnas.0911863107 Proto-oncogene tyrosine-protein kinase Src 5
20439741 10.1073/pnas.0911863107 Serine/threonine-protein kinase D2 5
20439741 10.1073/pnas.0911863107 Tyrosine-protein kinase Yes 5
20439741 10.1073/pnas.0911863107 Ribosomal protein S6 kinase alpha-1 5
20439741 10.1073/pnas.0911863107 Protein kinase C theta type 5
20439741 10.1073/pnas.0911863107 Ribosomal protein S6 kinase alpha-3 5

Data from ChEMBL 36 via Core Engine