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Compound Detail

CHEMBL1956285

DSM-265
🧪 Phase II
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🧪 Phase II
Cc1cc(Nc2ccc(S(F)(F)(F)(F)F)cc2)n2nc(C(C)(F)F)nc2n1

Basic Information

ChEMBL ID CHEMBL1956285
Name DSM-265
Phase Phase II
Structure Type MOL
InChI Key OIZSVTOIBNSVOS-UHFFFAOYSA-N

Known Names

Dsm-265 Dsm265
7
Targets
56
Activities
2
Assay Types
30
PK Parameters
20
Publications
2
Known Names
3
Indications
1
Mechanisms

Molecular Properties

415.3
MW (Da)
5.95
ALogP
5
HBA
1
HBD
55.1
PSA (Ų)
0.54
QED
1
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral

Extended Properties

Molecular Formula C14H12F7N5S
MW 415.34
Aromatic Rings 3
Heavy Atoms 27
NP-Likeness -1.53

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Dihydroorotate dehydrogenase inhibitor INHIBITOR Dihydroorotate dehydrogenase

Indications

Malaria, Falciparum Malaria, Vivax Malaria

Activity Summary

EC50 31 meas. best 8.37
IC50 25 meas. best 8.74

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Plasmodium falciparum
CHEMBL364
IC50 8.74 8.1667 1.8 6
Plasmodium falciparum
CHEMBL364
EC50 8.37 7.54 4.3 26
Unchecked
CHEMBL612545
IC50 8.05 6.8808 8.9 12
Dihydroorotate dehydrogenase
CHEMBL3486
IC50 8.0 7.74 10.0 2
Unchecked
CHEMBL612545
EC50 7.7 7.7 20.0 1
Plasmodium vivax
CHEMBL613013
EC50 6.72 6.5 190.0 2
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
EC50 5.8 5.48 1600.0 2
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.8 5.8 1600.0 1
Dihydroorotate dehydrogenase (quinone), mitochondrial
CHEMBL2991
IC50 5.68 5.66 2100.0 2
Dihydroorotate dehydrogenase (quinone), mitochondrial
CHEMBL2383
IC50 5.58 5.47 2600.0 2

Pharmacokinetic Data

Parameter Value Units Species
AUC 186.9 ng.hr.mL-1 Mus musculus
AUC 1128.48 ng.hr.mL-1 Mus musculus
AUC 9394.99 ng.hr.mL-1 Mus musculus
AUC 14038.49 ng.hr.mL-1 Mus musculus
AUC 6429.46 ng.hr.mL-1 Rattus norvegicus
AUC 50476.27 ng.hr.mL-1 Rattus norvegicus
AUC 133635.64 ng.hr.mL-1 Rattus norvegicus
AUC 24014.96 ng.hr.mL-1 Mus musculus
AUC 23724.22 ng.hr.mL-1 Mus musculus
AUC 16700.0 ng.hr.mL-1 Canis lupus familiaris
AUC 16700.0 ng.hr.mL-1 Macaca mulatta
AUC 107000.0 ng.hr.mL-1 Homo sapiens
AUC 12335.6 ng.hr.mL-1 Mus musculus
AUC 6479.3 ng.hr.mL-1 Rattus norvegicus
AUC 50671.48 ng.hr.mL-1 Rattus norvegicus
AUC 50671.48 ng.hr.mL-1 Rattus norvegicus
AUC 7226.92 ng.hr.mL-1 Rattus norvegicus
AUC 9386.68 ng.hr.mL-1 Mus musculus
CL 8.1 mL.min-1.g-1 Mus musculus
CL 5.0 mL.min-1.g-1 Homo sapiens
CL 3.6 mL.min-1.kg-1 Rattus norvegicus
CL 6.0 mL.min-1.kg-1 Rattus norvegicus
CL 0.3667 mL.min-1.kg-1 Canis lupus familiaris
CL 0.3667 mL.min-1.kg-1 Macaca mulatta
CL 6500.0 mL.min-1.g-1 Rattus norvegicus
CL 6.0 mL.min-1.kg-1 Rattus norvegicus
CL 263.0 mL.min-1.kg-1 Rattus norvegicus
Cmax 60.0 nM Mus musculus
Cmax 440.0 nM Mus musculus
Cmax 3100.0 nM Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Plasmodium falciparum IC50 = 1.8 nM 8.74 Antimalarial activity against Plasmodium falciparum NF54 33131885
Plasmodium falciparum IC50 = 2.6 nM 8.59 Antimalarial activity against Plasmodium falciparum K1 33131885
Plasmodium falciparum IC50 = 4.0 nM 8.4 Antiplasmodial activity against sorbitol-synchronized ring stage chloroquine sen... 38290351
Plasmodium falciparum IC50 = 4.3 nM 8.37 Antimalarial activity against wild type Plasmodium falciparum Dd2 29665687
Plasmodium falciparum EC50 = 4.3 nM 8.37 Antiplasmodial activity against Plasmodium falciparum 3D7 infected in RBC assess... 27127993
Plasmodium falciparum EC50 = 4.6 nM 8.34 Antimalarial activity against multidrug-resistant Plasmodium falciparum Dd2 meas... 32248693
Plasmodium falciparum EC50 = 5.0 nM 8.3 Antiplasmodial activity against asexual blood stage Plasmodium falciparum 3D7 in... 33620219
Plasmodium falciparum EC50 = 6.0 nM 8.22 Antimalarial activity against Plasmodium falciparum 3D7 infected in human red bl... 32248693
Plasmodium falciparum EC50 = 6.0 nM 8.22 Antimalarial activity against Plasmodium falciparum 3D70087/N9 infected in po do... 32248693
Plasmodium falciparum EC50 = 6.0 nM 8.22 Antiplasmodial activity against Plasmodium falciparum Dd2 infected in erythrocyt... 39024967
Plasmodium falciparum EC50 = 7.0 nM 8.15 Antimalarial activity against mefloquine/chloroquine-resistant Plasmodium falcip... 31385706
Plasmodium falciparum EC50 = 7.8 nM 8.11 Antimalarial activity against Plasmodium falciparum 3D7 by [3H]hypoxanthine inco... 21696174
Plasmodium falciparum EC50 = 7.8 nM 8.11 Antimalarial activity against Plasmodium falciparum 3D7 31385706
Unchecked IC50 = 8.9 nM 8.05 Inhibition of N-terminal His6-tagged Plasmodium falciparum DHODH expressed in Es... 27127993
Dihydroorotate dehydrogenase IC50 = 10.0 nM 8.0 Inhibition of Plasmodium falciparum DHODH expressed in Escherichia coli using L-... 31385706
Plasmodium falciparum IC50 = 12.0 nM 7.92 Antiplasmodial activity against sorbitol-synchronized ring stage 2-(1,1-difluoro... 38290351
Plasmodium falciparum EC50 = 15.0 nM 7.82 Antimalarial activity against atovoquone-resistant Plasmodium falciparum TM90C2B... 21696174
Unchecked EC50 = 20.0 nM 7.7 Inhibition of Plasmodium vivax DHODH expressed in Escherichia coli using L-dihyd... 31385706
Plasmodium falciparum EC50 = 22.0 nM 7.66 Antimalarial activity against drug-sensitive Plasmodium falciparum D6 by [3H]hyp... 21696174
Plasmodium falciparum EC50 = 23.0 nM 7.64 Antimalarial activity against Plasmodium falciparum 1D3 measured after 72 hrs by... 32248693

Literature References

PubMed DOI Target Context # Activities
27127993 10.1021/acs.jmedchem.6b00275 ADMET 29
32248693 10.1021/acs.jmedchem.0c00311 ADMET 28
21696174 10.1021/jm200592f Mus musculus 26
21696174 10.1021/jm200592f Rattus norvegicus 21
31385706 10.1021/acs.jmedchem.9b00761 Plasmodium falciparum 19
21696174 10.1021/jm200592f Plasmodium falciparum 12
32248693 10.1021/acs.jmedchem.0c00311 Plasmodium falciparum 11
32248693 10.1021/acs.jmedchem.0c00311 Unchecked 10
31385706 10.1021/acs.jmedchem.9b00761 ADMET 10
32248693 10.1021/acs.jmedchem.0c00311 No relevant target 7
38290351 10.1016/j.ejmech.2024.116163 Plasmodium falciparum 6
27127993 10.1021/acs.jmedchem.6b00275 No relevant target 5
21696174 10.1021/jm200592f Plasma 4
27127993 10.1021/acs.jmedchem.6b00275 Unchecked 3
29665687 10.1021/acs.jmedchem.8b00382 Plasmodium falciparum 3
32248693 10.1021/acs.jmedchem.0c00311 Dihydroorotate dehydrogenase (quinone), mitochondrial 3
21696174 10.1021/jm200592f Unchecked 3
30703745 10.1016/j.ejmech.2019.01.027 ADMET 3
31385706 10.1021/acs.jmedchem.9b00761 Plasmodium vivax 3
27127993 10.1021/acs.jmedchem.6b00275 Plasmodium falciparum 3

Data from ChEMBL 36 via Core Engine