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Compound Detail

CHEMBL4582651

PRALSETINIB
💊 Approved Drug
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💊 Approved Drug
CO[C@]1(C(=O)N[C@@H](C)c2ccc(-n3cc(F)cn3)nc2)CC[C@H](c2nc(C)cc(Nc3cc(C)[nH]n3)n2)CC1

Basic Information

ChEMBL ID CHEMBL4582651
Name PRALSETINIB
Phase Approved
Structure Type MOL
InChI Key GBLBJPZSROAGMF-RWYJCYHVSA-N
Therapeutic ✓ Yes

Known Names

:pralsetinib BLU-123244 Blu-667 BLU123244 Cis-pralsetinib Gavreto Pralsetinib Pralsetinib, cis- RG-6396 X-581238 X581238
4
Targets
21
Activities
1
Assay Types
6
PK Parameters
16
Publications
11
Known Names
5
Indications
3
Mechanisms

Molecular Properties

533.6
MW (Da)
4.20
ALogP
9
HBA
3
HBD
135.5
PSA (Ų)
0.31
QED
1
Ro5 Violations
8
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2020
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral
USAN Stem -tinib
USAN Year 2019

Extended Properties

Molecular Formula C27H32FN9O2
MW 533.61
Aromatic Rings 4
Heavy Atoms 39
NP-Likeness -1.35

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Tyrosine-protein kinase receptor RET inhibitor INHIBITOR Proto-oncogene tyrosine-protein kinase receptor Ret
Coiled-coil domain-containing protein 6/Tyrosine-protein kinase receptor RET inhibitor INHIBITOR Coiled-coil domain-containing protein 6/Tyrosine-protein kinase receptor RET
Kinesin-1 heavy chain/ Tyrosine-protein kinase receptor RET inhibitor INHIBITOR Kinesin-1 heavy chain/ Tyrosine-protein kinase receptor RET

Indications

Carcinoma, Medullary Carcinoma, Non-Small-Cell Lung Neoplasms Neoplasms Thyroid Neoplasms

ATC Classification

L01EX23
pralsetinib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 21 meas. best 9.52

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
IC50 9.52 9.1638 0.3 8
Tyrosine-protein kinase JAK2
CHEMBL2971
IC50 8.7 8.7 2.0 1
BaF3
CHEMBL614524
IC50 8.46 7.4891 3.5 11
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
IC50 8.19 8.19 6.5 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 24578.08 ng.hr.mL-1 Mus musculus
CL 38.0 mL.min-1.kg-1 Mus musculus
CL 5.0 mL.min-1.kg-1 Mus musculus
CL 8.6 mL.min-1.kg-1 Homo sapiens
F 77.2 % Mus musculus
Vd 0.7 L.kg-1 Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Proto-oncogene tyrosine-protein kinase receptor Ret IC50 = 0.3 nM 9.52 Inhibition of human RET V804L mutant 36395392
Proto-oncogene tyrosine-protein kinase receptor Ret IC50 = 0.4 nM 9.4 Inhibition of human wild type RET 36395392
Proto-oncogene tyrosine-protein kinase receptor Ret IC50 = 0.4 nM 9.4 Inhibition of human RET V804M mutant 36395392
Proto-oncogene tyrosine-protein kinase receptor Ret IC50 = 0.4 nM 9.4 Inhibition of His-tagged human recombinant wild type RET M918T mutant expressed ... 38484122
Proto-oncogene tyrosine-protein kinase receptor Ret IC50 = 0.7 nM 9.15 Inhibition of RET M918T mutant (unknown origin) 34058344
Proto-oncogene tyrosine-protein kinase receptor Ret IC50 = 0.78 nM 9.11 Inhibition of RET wild type (unknown origin) 34058344
Proto-oncogene tyrosine-protein kinase receptor Ret IC50 = 1.93 nM 8.71 Inhibition of RET V804M mutant (unknown origin) 34058344
Tyrosine-protein kinase JAK2 IC50 = 2.0 nM 8.7 Inhibition of JAK2 (unknown origin) 34058344
Proto-oncogene tyrosine-protein kinase receptor Ret IC50 = 2.4 nM 8.62 Inhibition of wild type rearranged during transfection kinase (unknown origin) p... 36308779
BaF3 IC50 = 3.5 nM 8.46 Antiproliferative activity against mouse BaF3 cells expressing rearranged during... 36308779
BaF3 IC50 = 4.1 nM 8.39 Antiproliferative activity against mouse BaF3 cells expressing rearranged during... 36308779
BaF3 IC50 = 4.4 nM 8.36 Antiproliferative activity against mouse BaF3 cells expressing wildtype rearrang... 36308779
BaF3 IC50 = 5.7 nM 8.24 Antiproliferative activity against mouse BaF3 cells expressing wildtype rearrang... 36308779
Receptor-type tyrosine-protein kinase FLT3 IC50 = 6.5 nM 8.19 Inhibition of FLT3 (unknown origin) 34058344
BaF3 IC50 = 9.2 nM 8.04 Antiproliferative activity against mouse BaF3 cells expressing rearranged during... 36308779
BaF3 IC50 = 17.0 nM 7.77 Antiproliferative activity against mouse KIF5B-RET BaF3 cells by cell based assa... 34058344
BaF3 IC50 = 21.7 nM 7.66 Antiproliferative activity against mouse BaF3 cells expressing rearranged during... 36308779
BaF3 IC50 = 215.0 nM 6.67 Antiproliferative activity against mouse BaF3 cells expressing rearranged during... 36308779
BaF3 IC50 = 241.0 nM 6.62 Antiproliferative activity against mouse BaF3 cells expressing rearranged during... 36308779
BaF3 IC50 = 575.0 nM 6.24 Antiproliferative activity against mouse BaF3 cells expressing rearranged during... 36308779

Literature References

PubMed DOI Target Context # Activities
36308779 10.1016/j.ejmech.2022.114862 BaF3 11
34058344 10.1016/j.bmcl.2021.128149 ADMET 9
34058344 10.1016/j.bmcl.2021.128149 Proto-oncogene tyrosine-protein kinase receptor Ret 3
36395392 10.1021/acs.jmedchem.2c01361 Proto-oncogene tyrosine-protein kinase receptor Ret 3
- 10.6019/CHEMBL4495565 SARS-CoV-2 2
32882611 10.1016/j.ejmech.2020.112755 Kinesin-1 heavy chain/ Tyrosine-protein kinase receptor RET 2
34058344 10.1016/j.bmcl.2021.128149 BaF3 2
- 10.6019/CHEMBL4495564 Replicase polyprotein 1ab 1
32882611 10.1016/j.ejmech.2020.112755 Coiled-coil domain-containing protein 6/Tyrosine-protein kinase receptor RET 1
32882611 10.1016/j.ejmech.2020.112755 Unchecked 1
32882611 10.1016/j.ejmech.2020.112755 BaF3 1
34058344 10.1016/j.bmcl.2021.128149 Tyrosine-protein kinase JAK2 1
34058344 10.1016/j.bmcl.2021.128149 Receptor-type tyrosine-protein kinase FLT3 1
36308779 10.1016/j.ejmech.2022.114862 Proto-oncogene tyrosine-protein kinase receptor Ret 1
- 10.6019/EOS300108 HepG2 1
38484122 10.1021/acs.jmedchem.3c02319 Proto-oncogene tyrosine-protein kinase receptor Ret 1

Data from ChEMBL 36 via Core Engine