World Malaria Day 2018

[mattodd]

...is on April 25th (a big Aussie public holiday as it happens).

What can we do as a community to mark this occasion? Calling for ideas.

In the past we have pushed social media messages to raise awareness, which is fine and valuable.

I wonder, though, if we could do something more concrete. A very good thing we could do is to aim to ship the next round of compounds to Dundee on that date (actually 24th). @edwintse @david1597 @maratsydney @mbhebhe - what say you? Reasonable?

Another thing we can do that is substantive is summarise the other molecules, not in the shipment, that are currently high value targets and bring peoples' attention to the ongoing synthetic work.

I wonder if @mcoster and @holeung and all others reading this Issue would be willing to prepare something written and short that describes current work relevant to OSM Series?

We could collate everything into a neat new Issue, and link to it on the day.

I will use the event as an excuse to (finally) send out the first newsletter (#547). This was delayed by a trivial thing I was waiting on, but which doesn't have a simple resolution, so I'll go ahead without it.

[david1597]

Yes - that'd be a great point at which to send the next shipment to Dundee. There should be 15-20 compounds between us.

Also great opportunity for distributing the first newsletter. Good stuff.

[cdsouthan]

As just tweeted, update/clean up the master sheet and surface it on figshare?

[mattodd]

That would be awesome of you, @cdsouthan.

[holeung]

Lovely! I'll write something up. Maybe we can do a press release?

[mcoster]

More than happy to write something up.

[cdsouthan]

@david1597 given I could get a least a few front runners into PubChem for WMD but to assist could you list out
a) how many sub-100 nM hits do we have in S4?
b) ditto sub-500 nM?

[edwintse]

@cdsouthan Here are the 10 sub-100 nM compounds for S4 (chemdraw attached)

Most Potent OSM S4.zip

As for the sub-500 nM ones, it'll take a bit longer to list (I suspect there are quite a few more) but we'll get back to you on that.

[mattodd]

...but @cdsouthan can you filter on the average potency in the Master List?

[cdsouthan]

1. @david1597 @edwintse Thanks, the sub 100s will do fine for now so don't bother with any more. I'll need full strings so perhaps one of you could just highlight in green the corresponding master-sheet rows and I can take it from there,

2. @mattodd Yes I have done this in the past but as mentioned before there are issues with averaging vs choosing an actual experimental result, e.g. where the values are discordant, extending above and below the threshold. Assuming that @david1597 @edwintse are (even informally) in charge of data collation I'll take their values

[cdsouthan]

Fine, but just for the record I was not trying to be lazy, its just that every extra manual operation has an error probability, especially any I have to do. Notwithstanding, I will try my damnedest to locate the correct string sets for all ll :)

[david1597]

Apologies for deleting Ed's comment. The table below contains the strings.

OSM ID	Internal ID	MMV ID	SMILES	InChI	IChI Key	IC50
OSM-S-377	INHERITED	MMV670652	FC(C=C1)=C(F)C=C1C(OC(F)F)COC2=CN=CC3=NN=C(C4=CC=C(C#N)C=C4)N32	InChI=1S/C21H13F4N5O2/c22-15-6-5-14(7-16(15)23)17(32-21(24)25)11-31-19-10-27-9-18-28-29-20(30(18)19)13-3-1-12(8-26)2-4-13/h1-7,9-10,17,21H,11H2	LHSRVKYAEUESTK-UHFFFAOYSA-N	16.7
OSM-S-381	INHERITED	MMV670947	FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(CO)C4=CC(F)=C(F)C=C4)N32	InChI=1S/C21H16F4N4O3/c22-16-6-3-13(7-17(16)23)14(10-30)11-31-19-9-26-8-18-27-28-20(29(18)19)12-1-4-15(5-2-12)32-21(24)25/h1-9,14,21,30H,10-11H2	MKSKANAVVSFYNL-UHFFFAOYSA-N	24.3
	INHERITED	MMV670945	FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC(OCCC4=CC=C(F)C(F)=C4)=CN32	InChI=1S/C20H14F4N4O2/c21-15-6-1-12(9-16(15)22)7-8-29-18-11-28-17(10-25-18)26-27-19(28)13-2-4-14(5-3-13)30-20(23)24/h1-6,9-11,20H,7-8H2	PHGWNHSKOAAQGR-UHFFFAOYSA-N	33.8
OSM-S-218	AEW 313-1	MMV669844/MMV897709	FC(C=C1)=C(F)C=C1C(OC)COC2=CN=CC3=NN=C(C4=CC=C(C#N)C=C4)N32	InChI=1S/C21H15F2N5O2/c1-29-18(15-6-7-16(22)17(23)8-15)12-30-20-11-25-10-19-26-27-21(28(19)20)14-4-2-13(9-24)3-5-14/h2-8,10-11,18H,12H2,1H3/t18-/m0/s1	PERKBMZWWUEZNJ-UHFFFAOYSA-N	40
	INHERITED	MMV670437	FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC@HC4=CC(F)=C(F)C=C4)N32	InChI=1S/C22H19F4N5O2/c1-30(2)18(14-5-8-16(23)17(24)9-14)12-32-20-11-27-10-19-28-29-21(31(19)20)13-3-6-15(7-4-13)33-22(25)26/h3-11,18,22H,12H2,1-2H3/t18-/m0/s1	PMIWBIXSAYKRGF-SFHVURJKSA-N	44.1
OSM-S-418	EGT 257-1	MMV1576784	FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC/C4=C/BBBBBBBBBB4)N32	InChI=1S/C16H22B10F2N4O2/c27-16(28)34-12-3-1-10(2-4-12)15-31-30-13-8-29-9-14(32(13)15)33-6-5-11-7-17-19-21-23-25-26-24-22-20-18-11/h1-4,7-9,16-26H,5-6H2/b11-7-	AGPVLTOPROUGPQ-XFFZJAGNSA-N	50
	INHERITED	MMV672936	FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(F)C4=CC=C(F)C(F)=C4)N32	InChI=1S/C20H13F5N4O2/c21-14-6-3-12(7-15(14)22)16(23)10-30-18-9-26-8-17-27-28-19(29(17)18)11-1-4-13(5-2-11)31-20(24)25/h1-9,16,20H,10H2	LWSXCRQHVHDFGX-UHFFFAOYSA-N	65.4
OSM-S-272	AEW 302-1	MMV639565	FC1=C(F)C=CC(CCOC2=CN=CC3=NN=C(C4=CC=C(Cl)C=C4)N32)=C1	InChI=1S/C19H13ClF2N4O/c20-14-4-2-13(3-5-14)19-25-24-17-10-23-11-18(26(17)19)27-8-7-12-1-6-15(21)16(22)9-12/h1-6,9-11H,7-8H2	PMHUSEXABGDNGS-UHFFFAOYSA-N	68.8
OSM-S-525	MK035-1	MMV1579341	FC1=CC(CCOC2=CN=CC3=NN=C(C4=CC=C5C(NC=C5)=C4)N32)=CC=C1F	InChI=1S/C21H15F2N5O/c22-16-4-1-13(9-17(16)23)6-8-29-20-12-24-11-19-26-27-21(28(19)20)15-3-2-14-5-7-25-18(14)10-15/h1-5,7,9-12,25H,6,8H2	VHFREJHLTSVZGA-UHFFFAOYSA-N	86
OSM-S-390	EGT 171-1	MMV672687	FC(OC1=CC=C(C2=NN=C3C=NC=C(N32)OCC(C4=CC(F)=C(C=C4)F)O)C=C1)F	InChI=1S/C20H14F4N4O3/c21-14-6-3-12(7-15(14)22)16(29)10-30-18-9-25-8-17-26-27-19(28(17)18)11-1-4-13(5-2-11)31-20(23)24/h1-9,16,20,29H,10H2	BXEWPSCIVPVASC-UHFFFAOYSA-N	99

Edited 16/4/18 to add InChIKey for OSM-S-218

[cdsouthan]

Just the job :)

[cdsouthan]

@david1597 please resolve

OSM-S-218	AEW 313-1	MMV669844/MMV897709

an include an InChIKey

[david1597]

@cdsouthan

I've edited my comment above to add the missing InChIKey.

The double MMV assignment relates to OpenSourceMalaria/Series4#35 and #470. OSM-S-218 is the compound which was resolved into it's enantiomers. I'm waiting to hear back from UCSD on the liver stage results (OpenSourceMalaria/Series4#35), and once that is clear we can fix up any other problems relating to these compounds.

[mattodd]

OK all, I've started the relevant GHI at #564

Please feel free to add a few lines about one thing you're working on. No need to make it comprehensive or pretty. Short and simple is good. Please try to include a link out to somewhere your work is (another Issue, for example) and, if you're able, add a photo to keep the page light. World Malaria Day is on Wednesday, so I'll probably start sharing #564 around Wed afternoon in Australia, and share a few more times as Europe and the US wakes up. So you have about 48 hours from the time of this message.

I'll keep this issue open for now, since we're still discussing a cheminformatics issue that has snuck in I think @cdsouthan ?

[cdsouthan]

1. have done my short piece What Open Source Malaria is Doing on World Malaria Day 2018 #564
2. Most of front-runners are now up at https://www.ncbi.nlm.nih.gov/pccompound?term=%22TW2Informatics%22%5BSourceName%5D&cmd=DetailsSearch
   there was an issue with one SMILES string that I need to check out. Note they are not yet expanded into BioAssay entries but I intend to do this in due course. JFTR the 2D and 3D neighbourhoods of these CIDs may take a week or so to be crunched
3. As I think was intended I will put a copy of the master-sheet on my figshare tomorrow