The Data on the Original Hit
The original hit for OSM Series 3 is the following compound, 3-(4-aminothieno[3,2-d]pyrimidin-6-yl)benzenesulfonamide.
SMILES: NC1=C2C(C=C(C3=CC=CC(S(=O)(N)=O)=C3)S2)=NC=N1
InChl: InChI=1S/C12H10N4O2S2/c13-12-11-9(15-6-16-12)5-10(19-11)7-2-1-3-8(4-7)20(14,17)18/h1-6H,(H2,13,15,16)(H2,14,17,18)
InChl key: MQMXDJVOZKMSNT-UHFFFAOYSA-N
Codes/data for this compound elsewhere: CHEMBL581088, Pubchem CID 44528665, TCMDC-135294, MMV025100, OSM-S-106, ZINC000045301248
Simple version:
With in vivo version:
OSM-S-106 — all test results in one: OSM-S-106_data allinone.xlsx
Calculated Compound Parent Properties:
| ALogP | Number of rotatable bonds | Polar Surface Area | Molecular Species | HBA | HBD | Ro5 Violations |
|---|---|---|---|---|---|---|
| 1.65 | 2 | 148.57 | Neutral | 5 | 2 | 0 |
Calculated physicochemical parameters using ChemAxon JChem software:
| MW | Polar Surface Area | Freely Rotating Bonds | HBD | HBA | Aromatic Rings | Fsp3 | cpKa | cLogP | cLogD (at pH 7.4) | gLogD (at pH 7.4) |
|---|---|---|---|---|---|---|---|---|---|---|
| 306.36 | 112.0 | 2 | 2 | 5 | 3 | 0 | Basic: 3.8 Acidic: 10.1 | 1.3 | 1.3 | 1.4 |
| GSK | Pfal IC50 (GSK) | Pfal IC50 (Dundee) | Pfal (Avery) | Single shot Inhibition |
|---|---|---|---|---|
| 0.036 uM | 0.088 uM | 0.13 uM | 0.036 uM | 102 uM |
OSM-S-106 was also evaluated in June/July 2018 at Dundee, giving values of ca. 100 nM.
| Solubility Range (ug/mL) | Solubility Range (ug/mL) |
|---|---|
| pH 2 | pH 6.5 |
| 50 - 100 | 12.5 - 25 |
| Solubility Range (ug/mL) | Solubility Range (ug/mL) |
|---|---|
| pH 2 | pH 6.5 |
| 50 - 100 | 6.3 - 12.5 |
| Species | Degradation half life (min) | CLint, in vitro(mL/min/mg protein) | Microsomal-Predicted CL blood(mL/min/kg) | Microsomal-Predicted | Degradation Rate Classification |
|---|---|---|---|---|---|
| Human | >247 | <7 | <5 | <0.22 | low |
| Mouse | 37 | 47 | 60 | 0.5 | Intermediate |
| Species | Degradation half life (min) | CLint, in vitro (uL/min/mg protein) | Predicted CLint, in vivo (mL/min/kg) | Predicted CLblood (mL/min/kg) | Predicted (EH) | Degradation Rate Classification |
|---|---|---|---|---|---|---|
| Human | >255 | <7 | <6 | <5 | <0.22 | low |
| Mouse | 23 | 76 | 196 | 74 | 0.62 | Intermediate |
Metabolic stability in rat cryopreserved hepatocytes
| Degradation half life (min) | In vitro CLint (uL/min/106) cells | Predicted CLint(mL/min/kg) | Predicted CLblood(mL/min/kg) | Hepatocyte Predicted (EH) | Degradation Rate Classification |
|---|---|---|---|---|---|
| >375 | <1 | <5 | <5 | <0.07 | low |
OSM-S-106 was sent to Pfizer for an in vitro biofunctionalisation experiment (April 2018) - data have not been posted anywhere yet.
| Species tested | Assay plate conc (uM) | Assay tested | Parasite IC50 (uM) | STD Parasite IC50 or 95% Confidence Intervals | Max % parasite inhibition | HepG2 IC50 (uM) |
|---|---|---|---|---|---|---|
| P.berghei | 10 | Luciferase Envision | 2.348 | 0.7453 to 7.396 | 98.87% | >10 |
| In vitro potency (uM) | hERG IC50 (uM) | hERG pcIC50 |
|---|---|---|
| 0.11 | >10 | <5.00 |
There is a limited amount of screening data for OSM-S-106 (CHEMBL581088) in ChEMBL, the only significant activity recorded was against Plasmodium falciparum.
A May 2022 summary of the data on the original hit:
2024 Summary of Dundee DMPK Data for OSM Compounds
| DDDID | Batch | DNDi ID | Purity (%) | Solubility (µM) | CHI logD | HepG2 pIC₅₀ | Microsomal Clearance (mL/min/mg) | T½ (min) |
|---|---|---|---|---|---|---|---|---|
| DDD00115078 | 3 | OSM-S-106 | 99 | 19.6 | — | 4.21 | 0.079075 | 17.53 |
| DDD02590662 | 1 | OSM-LO-80 | 99 | NR | — | 4.67 | 0.099054 | 13.99 |
| DDD02590664 | 1 | OSM-LO-87 | 99 | 16.9 | — | <4 | 0.152101 | 9.11 |
NR = Not Reported; “<4” in pIC₅₀ = low cytotoxicity DNDi Dundee DMPK Data OSM[82].xlsx DNDi_Gisele.Project_Nov2023[50].pptx