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

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

Potency data :

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

Solubility Range (ug/mL)	Solubility Range (ug/mL)
pH 2	pH 6.5
50 - 100	12.5 - 25

Solubility June 2018

Solubility Range (ug/mL)	Solubility Range (ug/mL)
pH 2	pH 6.5
50 - 100	6.3 - 12.5

Microsomal Stability

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

Metabolic Stability May 2018

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.

Liver stage malaria activity

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

hERG

In vitro potency (uM)	hERG IC50 (uM)	hERG pcIC50
0.11	>10	<5.00

Late Stage Gametocyte Assay

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: