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Compound Detail

CHEMBL159052

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NC1=NC(c2cccc(OCCCOc3cc(Cl)c(Cl)cc3Cl)c2)N(c2cccc(Cl)c2)C(N)=N1

Basic Information

ChEMBL ID CHEMBL159052
Phase Preclinical
Structure Type MOL
InChI Key JGKAPLMXNSTCCA-UHFFFAOYSA-N
5
Targets
15
Activities
2
Assay Types
0
PK Parameters
5
Publications
0
Known Names

Molecular Properties

553.3
MW (Da)
6.30
ALogP
7
HBA
2
HBD
98.5
PSA (Ų)
0.25
QED
2
Ro5 Violations
8
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C24H21Cl4N5O2
MW 553.28
Aromatic Rings 3
Heavy Atoms 35
NP-Likeness -0.92

Activity Summary

IC50 10 meas. best 6.43
Ki 5 meas. best 8.7

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL1939
Ki 8.7 8.54 2.0 5
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL1939
IC50 6.43 5.4883 370.0 6
KB
CHEMBL398
IC50 5.16 5.16 7000.0 1
Plasmodium falciparum
CHEMBL364
IC50 5.05 5.05 9000.0 1
BC
CHEMBL613535
IC50 5.0 5.0 10000.0 1
Vero
CHEMBL391
IC50 4.75 4.75 18000.0 1

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Bifunctional dihydrofolate reductase-thymidylate synthase Ki = 2.0 nM 8.7 Binding affinity towards mutant dihydrofolate reductase (N51I+C59R+S108N DHFR) o... 14736247
Bifunctional dihydrofolate reductase-thymidylate synthase Ki = 2.2 nM 8.66 Binding affinity towards mutant dihydrofolate reductase (C59R+S108N+I164L DHFR) ... 14736247
Bifunctional dihydrofolate reductase-thymidylate synthase Ki = 2.6 nM 8.59 Binding affinity towards mutant dihydrofolate reductase (A16V+S108T DHFR) of Pla... 14736247
Bifunctional dihydrofolate reductase-thymidylate synthase Ki = 4.0 nM 8.4 Binding affinity towards wild-type dihydrofolate reductase of Plasmodium falcipa... 14736247
Bifunctional dihydrofolate reductase-thymidylate synthase Ki = 4.5 nM 8.35 Binding affinity towards mutant dihydrofolate reductase (N51I+C59R+S108N+I164L D... 14736247
Bifunctional dihydrofolate reductase-thymidylate synthase IC50 = 370.0 nM 6.43 In vitro anti-plasmodial activity against Plasmodium falciparum dihydrofolate re... 14736247
Bifunctional dihydrofolate reductase-thymidylate synthase IC50 = 3000.0 nM 5.52 In vitro anti-plasmodial activity against Plasmodium falciparum dihydrofolate re... 14736247
Bifunctional dihydrofolate reductase-thymidylate synthase IC50 = 3200.0 nM 5.5 In vitro anti-plasmodial activity against Plasmodium falciparum dihydrofolate re... 14736247
Bifunctional dihydrofolate reductase-thymidylate synthase IC50 = 5200.0 nM 5.28 In vitro anti-plasmodial activity against Plasmodium falciparum dihydrofolate re... 14736247
KB IC50 = 7000.0 nM 5.16 In vitro cytotoxicity against Plasmodium falciparum infected KB cell line 14736247
Bifunctional dihydrofolate reductase-thymidylate synthase IC50 = 7400.0 nM 5.13 In vitro anti-plasmodial activity against Plasmodium falciparum dihydrofolate re... 14736247
Bifunctional dihydrofolate reductase-thymidylate synthase IC50 = 8600.0 nM 5.07 In vitro anti-plasmodial activity against Plasmodium falciparum dihydrofolate re... 14736247
Plasmodium falciparum IC50 = 9000.0 nM 5.05 Antimicrobial activity against Plasmodium falciparum 20185316
BC IC50 = 10000.0 nM 5.0 In vitro cytotoxicity against Plasmodium falciparum infected BC cell line. 14736247
Vero IC50 = 18000.0 nM 4.75 In vitro cytotoxicity against Plasmodium falciparum infected vero cell line. 14736247

Literature References

PubMed DOI Target Context # Activities
14736247 10.1021/jm030165t Bifunctional dihydrofolate reductase-thymidylate synthase 15
14736247 10.1021/jm030165t Vero 5
14736247 10.1021/jm030165t KB 4
14736247 10.1021/jm030165t BC 3
20185316 10.1016/j.bmc.2010.01.068 Plasmodium falciparum 1

Data from ChEMBL 36 via Core Engine