Ora Biomedical Million Molecule Challenge Results

[Josh]

Ora reply
"Data output and leaderboard updates have been quite a bit slower than acceptable. Since beginning of the year, we have increased support around benchtop and database operations so we can improve. Things are moving well internally now, but there is still a delay while a new bolus of experiments finishes and is added to the database and leaderboard. I expect we should start seeing regular updates to the database and leaderboard by end of February.

Yes, antibiotic effects are definitely a driver of lifespan effect in some compounds on the database. Our imaging data can pretty accurately identify whether a compound is having an effect on bacterial outgrowth. Killing or growth arresting the animal food source also has lifespan effects, and so there is an open debate about best practices in the field. I think building in a selection for food type is an interesting idea. We can accommodate that in custom contracts now, and I will make sure we keep that in mind when we move forward with updating the MMC store.

Thank you again for reaching out and apologies for the continued delays."

[DeStrider]

The ITP does not use fat and diabetic mice. I am not sure where you got that information. If they did, Rapamycin would not have increased their lifespan.

A study DID test Rapamycin on fat and diabetic mice and found that it DECREASED lifespan. The diabetic mice died of inflammatory diseases instead of primarily from cancer when given Rapamycin. So, if you are fat and diabetic, you should not take Rapamycin as it may have the opposite effect and reduce your lifespan by increasing inflammation.

[Josh]

We need to ask ora for a csv of all results we can feed into ai. Now i have to manually combine combo and solo tables and convert them and pick just a few columns

[AnUser]

@Josh

Now i have to manually combine combo and solo tables and convert them and pick just a few columns

Treatment,Dose,Username,Median Lifespan,Animals Tested,Replicate Populations,Median Lifespan (Control),Animals Tested (Control),Replicate Populations (Control),% Change in Median Lifespan,Logrank p-Value,Temp (C)
Doxycycline HCl,10uM,Rapamycin Longevity Lab,21.8,69,6,14,71,6,55.7,< .001,20
Doxycycline HCl,10uM,Rapamycin Longevity Lab,21.8,69,6,14,71,6,55.7,< .001,20
Sulforaphane,50uM,Anonymous,20,113,6,14,88,6,42.9,< .001,20
Azathioprine,50uM,adssx,19.8,66,6,14,71,6,41.4,< .001,20
Nilvadipine,10uM,JakLemur,17.9,66,4,12.9,85,4,38.8,< .001,20
GSK2126458,10uM,Rapamycin Longevity Lab,22.9,64,3,17,60,3,34.7,< .001,20
D-Mannitol,50uM,Anonymous,19.9,96,6,15.8,113,6,25.9,< .001,20
Xylose,50uM,Anonymous,19.9,101,6,15.8,113,6,25.9,< .001,20
Carvedilol,50uM,adssx,20.8,70,6,16.7,87,6,24.6,0.076,20
Pramiracetam,50uM,Beth1708,18.9,88,6,15.8,113,6,19.6,0.053,20
Metolazone,50uM,Anonymous,18.9,82,6,15.8,113,6,19.6,0.124,20
Doxycycline HCl,50uM,Staffan Olsson,19.6,51,3,16.5,60,4,18.8,0.128,20
Doxycycline HCl,50uM,Staffan Olsson,19.6,51,3,16.5,60,4,18.8,0.128,20
Berberine,50uM,AmyBKillen,20.8,48,3,17.8,53,3,16.9,< .001,20
Punicalagin,50uM,Contender,20.8,45,3,17.8,53,3,16.9,< .001,20
Oxethazaine,10uM,Mr Wormboto,14.9,75,4,13,73,4,14.6,0.002,20
Benidipine HCl,10uM,Tithonus,15,64,4,13.1,71,4,14.5,< .001,20
Spermidine trihydrochloride,50uM,Carl Lumma,19.7,55,5,17.3,52,5,13.9,0.185,20
Enoxacin,10uM,Josef P.,14.9,72,4,13.1,58,3,13.7,0.001,20
Glycine,50uM,Nate Sticco,15.8,85,6,14,71,6,12.9,0.101,20
Glycine,50uM,Nate Sticco,15.8,85,6,14,71,6,12.9,0.101,20
Hydralazine HCl,100uM,adssx,15.8,80,6,14,71,6,12.9,0.005,20
Florfenicol,10uM,Josef P.,14.5,92,4,12.9,92,4,12.4,< .001,20
Linoleic Acid,50uM,Matt Yousefzadeh,19.9,47,3,17.8,53,3,11.8,0.024,20
Vanillin,50uM,LinusPetersson,19.9,37,2,17.8,53,3,11.8,0.017,20
Astaxanthin,1uM,Flatlander Woman,18.9,56,3,17,60,3,11.2,0.53,20
Berberine hydrochloride,50uM,Anonymous,20.1,61,6,18.1,89,6,11,0.003,20
Oleic Acid,10uM,Contender,16,41,3,14.8,38,3,8.1,0.238,20
Daptomycin,50uM,Mr Wormboto,14.9,65,3,13.8,53,3,8,0.992,20
Taurine,50uM,Ray Melissa,16,35,3,14.9,43,3,7.4,0.166,20
Nitazoxanide,10uM,Mr Wormboto,14.9,88,4,13.9,71,4,7.2,0.048,20
Naftopidil,10uM,Mr Wormboto,14.9,62,4,13.9,88,4,7.2,0.163,20
(-)-Epigallocatechin gallate,1uM,Anonymous,15,96,6,14,88,6,7.1,0.907,20
Coenzyme Q10,1nM,adssx,16.9,88,6,15.8,91,6,7,0.951,20
Azelnidipine,10uM,Luis Arturo Galindo,14,67,4,13.1,71,4,6.9,0.029,20
Phenformin HCl,10uM,Milie,14,71,4,13.1,81,4,6.9,0.282,20
D-(-)-Salicin,50uM,matthost,17.8,89,6,16.7,87,6,6.6,0.478,20
ORY-1001,50uM,Anonymous,20,73,5,18.8,60,5,6.4,0.696,20
Cysteamine HCl,50uM,Estéfano Pinilla,18.9,58,3,17.8,54,3,6.2,0.364,20
5-Azacytidine,50uM,Edward,18.9,53,3,17.8,54,3,6.2,0.201,20
Puromycin dihydrochloride,50uM,The Macrobian,18.9,49,3,17.8,53,3,6.2,0.064,20
Capsaicin,50uM,Andy Jones,18.9,42,3,17.8,54,3,6.2,0.3,20
Biotin,50uM,NKOAS,18.9,60,3,17.8,54,3,6.2,0.049,20
Quercetin,50uM,Anonymous,18.9,43,3,17.8,53,3,6.2,0.02,20
Daidzein,50uM,Anonymous,18.9,45,3,17.8,53,3,6.2,0.044,20
Sitagliptin,50uM,adssx,17.5,49,3,16.5,60,4,6.1,0.908,20
Luteolin,10uM,Staffan Olsson,17.5,44,3,16.5,60,4,6.1,0.504,20
Dihydromyricetin,50uM,Staffan Olsson,17.5,38,3,16.5,60,4,6.1,0.53,20
Resveratrol,50uM,The.Cole,18.8,60,3,17.8,54,3,5.6,0.761,20
Diphenhydramine HCl,50uM,Alex Kesin,18.8,44,3,17.8,53,3,5.6,0.181,20
Thymidine,50uM,Singularity,18.8,58,3,17.8,53,3,5.6,0.012,20
Leflunomide,50uM,Dan R,18.8,62,3,17.8,54,3,5.6,0.351,20
L-Theanine,10uM,Carl Lumma,17.9,51,5,17.3,52,5,3.5,0.739,20
atorvastatin,50uM,adssx,17,44,3,16.5,60,4,3,0.785,20
UTP, Trisodium Salt,50uM,Flatlander Woman,17,48,3,16.5,45,4,3,0.656,20
Osthole,50uM,Estéfano Pinilla,18.3,44,3,17.8,53,3,2.8,0.151,20
Rosuvastatin,50uM,RXB,18.3,40,3,17.8,54,3,2.8,0.987,20
Baicalin,50uM,matthost,18.3,52,3,17.8,53,3,2.8,0.083,20
Amitriptyline HCl,50uM,Tracy Hughes,17.4,44,3,17,34,3,2.4,0.871,20
Pentadecanoic Acid,1uM,Anonymous,16.1,78,6,16,74,6,0.6,0.923,20
Pentadecanoic Acid,1uM,Anonymous,16.1,78,6,16,74,6,0.6,0.923,20
Miglitol,50uM,Anonymous,15.9,110,6,15.8,113,6,0.6,0.476,20
Rapamycin (Sirolimus),15uM,Mr Wormboto,17,74,3,17,60,3,0,0.795,20
Rapamycin (Sirolimus),15uM,Brice,17,58,3,17,60,3,0,0.996,20
Temsirolimus,10uM,Rapamycin Longevity Lab,17,49,3,17,60,3,0,0.501,20
Ridaforalimus,10uM,Rapamycin Longevity Lab,17,50,3,17,60,3,0,0.823,20
Cobicistat,10uM,Mr Wormboto,13.9,77,4,13.9,87,4,0,0.478,20
Rapamycin (Sirolimus),15uM,Mr Wormboto,17,74,3,17,60,3,0,0.795,20
Rapamycin (Sirolimus),15uM,Brice,17,58,3,17,60,3,0,0.996,20
Chenodeoxycholic Acid,50uM,ChenNan,17.8,57,3,17.8,53,3,0,0.931,20
Naltrexone HCl,50uM,Neilvas,17.8,53,3,17.8,54,3,0,0.33,20
Loperamide HCl,10uM,The.Cole,13.1,75,4,13.1,62,4,0,0.642,20
Furaltadone HCl,10uM,JJ,12.9,88,4,12.9,87,4,0,0.787,20
Acarbose,50uM,JJ,17.8,63,3,17.8,54,3,0,0.612,20
Z-Ligustilide,50uM,Contender,17.8,77,3,17.8,53,3,0,0.443,20
Homoharringtonine,50uM,The Macrobian,17.8,75,3,17.8,53,3,0,0.353,20
Doxapram HCl,10uM,Josef P.,13.1,77,4,13.1,55,3,0,0.584,20
Pioglitazone HCl,10uM,jeffj,13.9,85,4,13.9,75,4,0,0.25,20
Rapamycin (Sirolimus),15uM,Mr Wormboto,17,74,3,17,60,3,0,0.795,20
Rapamycin (Sirolimus),15uM,Brice,17,58,3,17,60,3,0,0.996,20
Valsartan,50uM,Ryan Brashear MD,17.8,57,3,17.8,49,3,0,0.205,20
Losartan,50uM,Ryan Brashear MD,17.8,55,3,17.8,54,3,0,0.606,20
Irbesartan,50uM,Ryan Brashear MD,17.8,43,3,17.8,54,3,0,0.487,20
Abiraterone acetate,10uM,Spudnut,15.9,52,3,15.9,57,3,0,0.805,20
Prednisone,50uM,Spudnut,17.8,68,3,17.8,53,3,0,0.74,20
Dehydroepiandrosterone (DHEA),50uM,Dr.StevenWiniarski,17.8,79,3,17.8,54,3,0,0.797,20
Amoxicillin,50uM,Flatlander Woman,17.8,76,3,17.8,54,3,0,0.391,20
Ciprofibrate,10uM,schmiddl,13.9,79,4,13.9,74,4,0,0.176,20
Tetracaine HCl,10uM,Anonymous,13.1,89,4,13.1,71,4,0,0.27,20
Esomeprazole Sodium,10uM,Anonymous,13.1,67,4,13.1,77,4,0,0.627,20
N-acetyl-D-Glucosamine,50uM,HealthierFriends.org,17.8,42,3,17.8,53,3,0,0.219,20
Aspirin (Acetylsalicylic acid),50uM,kabelsalat,17.8,44,3,17.8,54,3,0,0.482,20
Aminoglutethimide,10uM,Hazes,13.1,65,4,13.1,77,4,0,0.535,20
Metoprolol Succinate,H2O,Beth,13.9,45,2,13.9,37,2,0,0.886,20
Capsaicin,50uM,Ferdinando.randisi,17.8,36,2,17.8,53,3,0,0.707,20
xanthine,50uM,Ferdinando.randisi,17.8,50,3,17.8,53,3,0,0.419,20
Pomalidomide (CC-4047),H2O,Beth,14,30,2,14,159,9,0,0.447,20
Bilirubin,1uM,Petr Malik,17,54,3,17,60,3,0,0.828,20
Telmisattan,10uM,adssx,17,57,3,17,60,3,0,0.903,20
Dapagliflozin,50uM,adssx,17,43,3,17,60,3,0,0.31,20
Ezetimibe,10uM,adssx,17,57,3,17,60,3,0,0.751,20
Ezetimibe,10uM,adssx,17,57,3,17,60,3,0,0.751,20
Isradipine (Dynacirc),10uM,adssx,16.5,37,3,16.5,60,4,0,0.674,20
Indapamide,50uM,adssx,16.5,31,3,16.5,60,4,0,0.934,20
Lithium Citrate,50uM,adssx,16.5,49,3,16.5,60,4,0,0.05,20
Naphazoline HCl,50uM,adssx,16.5,49,3,16.5,60,4,0,0.408,20
Flecainide acetate,50uM,adssx,16.5,50,3,16.5,60,4,0,0.199,20
Allantoin,50uM,Rapamycin Longevity Lab,16.5,43,3,16.5,45,4,0,0.484,20
Glycine,50uM,Anonymous,15,85,6,15,66,6,0,0.46,20
Alpha-L-rhamnose,50uM,happyfunball,15.7,55,6,15.7,52,6,0,0.829,20
Glycine,50uM,Anonymous,15,85,6,15,66,6,0,0.46,20
Pentadecanoic Acid,1uM,Anonymous,16,90,6,16,74,6,0,0.809,20
Pentadecanoic Acid,1uM,Anonymous,16,90,6,16,74,6,0,0.809,20
Piperlongumine,50uM,Anonymous,14,112,6,14,88,6,0,0.53,20
Metronidazole,50uM,Zack,17.1,99,6,17.1,94,6,0,0.484,20
Torsemide,50uM,Anonymous,15.8,91,6,15.8,113,6,0,0.265,20
Fargesin,50uM,Contender,16.4,60,3,16.5,60,4,-0.6,0.914,20
Lutein,10uM,Petr Malik,16.5,44,3,17,60,3,-2.9,0.511,20
Terazosin HCl,50uM,adssx,16,50,3,16.5,60,4,-3,0.29,20
Metformin HCl,50uM,Rapamycin Longevity Lab,16,38,3,16.5,60,4,-3,0.202,20
Hyoscyamine,50uM,Max Unfried,16.9,44,3,17.8,54,3,-5.1,0.936,20
Hyaluronic acid sodium salt,50uM,Flatlander Woman,15.6,45,3,16.5,45,4,-5.5,0.411,20
Hydrochlorothiazide,50uM,adssx,15.6,57,3,16.5,60,4,-5.5,0.719,20
Bimatoprost,50uM,adssx,15.6,49,3,16.5,60,4,-5.5,0.15,20
NAD+,50uM,MKing,15,46,3,15.9,57,3,-5.7,0.998,20
AICAR,50uM,Mr Wormboto,16,44,3,17,34,3,-5.9,0.829,20
Rapamycin (Sirolimus),15uM,Rapamycin Longevity Lab,15.9,53,3,17,60,3,-6.5,0.9,20
Everolimus (RAD001),10uM,Rapamycin Longevity Lab,15.9,52,3,17,60,3,-6.5,0.095,20
Rapamycin (Sirolimus),15uM,Rapamycin Longevity Lab,15.9,53,3,17,60,3,-6.5,0.9,20
Rapamycin (Sirolimus),15uM,Rapamycin Longevity Lab,15.9,53,3,17,60,3,-6.5,0.9,20
Kaempferol,10uM,Contender,15.9,45,3,17,60,3,-6.5,0.957,20
Canagliflozin,50uM,adssx,15.9,60,3,17,60,3,-6.5,0.753,20
Canagliflozin,50uM,Anonymous,14.6,55,6,15.7,67,6,-7,0.923,20
Dapagliflozin,50uM,Anonymous,14.6,58,6,15.7,67,6,-7,0.845,20
Amlodipine,10uM,Anonymous,12,77,4,13.1,71,4,-8.4,0.554,20
Venlafaxine,50uM,Anonymous,17,62,5,18.8,60,5,-9.6,0.589,20
Nordihydroguaiaretic acid,50uM,Rapamycin Longevity Lab,15.9,55,3,17.8,54,3,-10.7,0.754,20
Scopolamine butylbromide,50uM,Max Unfried,15.9,69,3,17.8,53,3,-10.7,0.299,20
Dimethyl Fumarate,50uM,Rapamycin News,15.9,40,3,17.8,53,3,-10.7,0.198,20
Flavone,50uM,Anonymous,15.9,69,3,17.8,53,3,-10.7,0.071,20
Tadalafil,50uM,Anonymous,15.9,55,3,17.8,54,3,-10.7,0.797,20
Curcumin,10uM,WiseAthletes Podcast,15,70,3,17,60,3,-11.8,0.195,20
ABT-263 (Navitoclax),10uM,Anonymous,15,60,3,17,60,3,-11.8,0.045,20
Empagliflozin (BI 10773),50uM,adssx,15,55,3,17,60,3,-11.8,0.265,20
Lithium carbonate,50uM,adssx,14.5,43,3,16.5,45,4,-12.1,0.715,20
Dasatinib (BMS-354825),50uM,Mr Wormboto,14.9,39,3,17,34,3,-12.4,0.027,20
VX-222 (VCH-222, Lomibuvir),10uM,beng,14.9,53,3,17,34,3,-12.4,0.124,20
Artesunate,50uM,Beth,14.9,53,3,17,34,3,-12.4,0.264,20
Nevirapine,10uM,Mr Wormboto,12,69,4,13.9,85,4,-13.7,0.536,20
Apigenin,50uM,Anonymous,15.3,30,2,17.8,53,3,-14,0.196,20
Pterostilbene,50uM,Anonymous,14.8,44,3,17.8,53,3,-16.9,0.012,20
Miconazole,50uM,The Macrobian,14.7,56,3,17.8,53,3,-17.4,0.175,20
Montelukast Sodium,10uM,starchild,13.9,44,3,17,60,3,-18.2,0.194,20
Dutasteride,10uM,TM5614Hairmine,13.9,41,3,17,60,3,-18.2,0.017,20
Ezetimibe,10uM,Ben Nashman,13.9,46,3,17,34,3,-18.2,0.002,20
Ezetimibe,10uM,Ben Nashman,13.9,46,3,17,34,3,-18.2,0.002,20
Fenbendazole,10uM,Mr Wormboto,11.9,58,3,17,34,3,-30,< .001,20
Albendazole Oxide,50uM,Mr Wormboto,11,86,3,17.9,63,3,-38.5,< .001,20
MLN2238,50uM,The Macrobian,5.6,48,3,16.5,60,4,-66.1,< .001,20

Is this correct? I copy pasted the whole solo table to Mistral (Mistral AI | Frontier AI in your hands) and asked it to convert it. Apparently it was just tab separated then. The free tiers of the other LLM’s had a limit on how much they could generate.

[Josh]

I think visually with descriptions will probably be easiest to convey bacterial effects. I like the rating systems too; we’ll have to think a bit more about that.

With many of the antibiotic effects we have seen, the animals end up eating through the bacteria during the assay and likely become dietarily restricted in late life. That makes it very difficult to decouple between DR and suppression of dysbiosis (which is known to shorten worm lifespan) when assessing longevity effects.

Providing a .csv of results should be no problem at all and Ben can get those to you."

[Satchel]

In my practice, most farmed (non-organic) animals grow bigger and healthier when fed a low level of antibiotics. Hard to say if healthspan equates to extended lifespan since we eat them somewhat earlier!. Also the biggest improvements are seen in the most crowded conditions-think poultry cages/cattle feedlots where respiratory and gi infections are endemic.-so i wonder if all the c. elegans effects are crowded “cage conditions” - do c. elegans get a cough?

[Josh]

Sponsored Loxapine succinate since it was Grok’s top one hadn’t been sponsored yet, expecting 40%

[Josh]

Found another paper that “screened for compounds that increase C. elegans longevity using a library of 1280 compounds” and found 2 over +40% and 14 the 30-39%

A pharmacological network for lifespan extension in Caenorhabditis elegans

[Josh]

"Dear MMC Sponsor,

I wanted to reach out personally and give you an update on some of the ongoing research at Ora Biomedical that includes one or more of your sponsored interventions. You may have already reached out, but in case you hadn’t we wanted to get in touch to let you know that your outstanding data is still on its way to you (and the MMC leaderboard if you opted-in to open-access). I know this is outside our expected turnaround time and I very much want to thank you for your patience.

As the sponsorship program launched, then quickly grew, we found ourselves in need of additional research infrastructure and processes to expedite retesting of interventions flagged during our QC. Over the last three months, we have scaled our team up, built tracking processes, and overcame a reagent issue that caused many interventions to require retesting. Producing the best quality, most reliable data as quickly as possible has always been our mission. We have fallen short of that with one or more of your tests. I greatly apologize and want to assure you that these issues are in the past.

Your remaining intervention tests are being conducted now at no additional cost to you. Many of these tests are close to concluding and we will expedite the return of sponsored data as soon as the experiments wrap-up. We sincerely thank you for your continued support of Ora Biomedical and the Million Molecule Challenge."

Im confused about test at no cost since we already paid. Maybe they mean retested no cost (with fix)?

[Bicep]

It says “no additional cost” and they had a reagent issue that required retesting.

[relaxedmeatball]

Am I correct here in saying that so far I don’t think of the results from this have been helpful in terms of identifying geroprotective molecules? I love the idea, especially the crowd sourcing, relative simplicity, and the open nature of the results.

However:

Rapamycin has failed every dose tested

The ones which do work seem to be ‘gaming’ the assay itself, such as antibiotics which affect the food source. I highly doubt they’re working on fundamental longevity pathways.

Worms don’t have heart attacks, kidney issues or glucose/insulin issues. Thus things like Metformin, SGLT2i etc also fail. Fair enough. Those are more like treating age-related diseases IMO.

Berberine is really puzzling. Probably the most interesting on the leader board IMO.

Therefore, so far it seems we haven’t identified anything which prevents aging on a more fundamental basis. The search continues.

[Josh]

It was always the Million Molecule challenge not the 100. And rapamycin does work in conjunction with other things as do other mtor inhibitors like the one all over the leaderboard.
Really just the one leading antibiotic that is suspect, but other studies show that it provides some life extension even with uv killed food.

[Josh]

It looks like there’s been an update with various smaller doses winning against standard, and we even see Rapamycin on leaderboard now above a lot of the GSK mtor combos

[adssx]

3 results:

Ursodiol (UDCA) +5% with long-lived controls (poke @Yoo):

Methylcobalamin -10%:

Methotrexate -10%:

UDCA failed in the ITP. I’m waiting for the TUDCA results.

[dicarlo2]

Interesting that methotrexate failed. I wonder how comparable the immune system is of worms to mice to humans. Was the dose used a chemo or autoimmune level of dosing?

Notably, the leaderboard does not have any other immunosuppressive/modulating drugs, aside from Rapamycin/other mTOR inbibitors.

[Curious]

There have been some problems with the wormbot. I got a weird result.

Order-9191-Doxycycline-HCl-50uM-±-GSK2126458-10uM-report_final.pdf (416.5 KB)

[adssx]

@dicarlo2

Notably, the leaderboard does not have any other immunosuppressive/modulating drugs, aside from Rapamycin/other mTOR inbibitors.

There’s azathioprine.

[adssx]

Hum. Did you tell them?

[Curious]

I will write to them now…And if my worms is still alive then it is world record

[adssx]

Longevity escape velocity!