NPASS Compound

Natural Product: NPC491013

Natural Product ID	NPC491013
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Ergosterol
IUPAC Name	(3S,9S,10R,13R,14R,17R)-17-[(E,2R,5R)-5,6-dimethylhept-3-en-2-yl]-10,13-dimethyl-2,3,4,9,11,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-ol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	444679
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003567] Ergostane steroids [CHEMONTID:0001403] Ergosterols and derivatives

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 73 76 0 0 0 0 0 0 0 0999 V2000 2.1175 1.9009 -1.3422 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3078 0.7944 -0.3300 C 0 0 2 0 0 0 0 0 0 0 0 0 3.6546 0.2090 -0.5453 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5304 0.2369 0.4387 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9095 -0.3287 0.3114 C 0 0 2 0 0 0 0 0 0 0 0 0 6.0434 -1.3841 1.3863 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8666 0.8248 0.5559 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6448 1.9174 -0.4601 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2699 0.2856 0.4336 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2393 -0.2302 -0.5145 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4292 -1.3924 0.4887 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0456 -1.9156 0.8035 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7923 -1.1927 -0.1948 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1472 0.1855 -0.1242 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8613 1.1190 -1.0197 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2689 1.2636 -0.4142 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9828 -0.0596 -0.5912 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2066 -1.0751 0.1408 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7828 -1.8159 1.0795 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1956 -1.6794 1.3824 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9724 -0.8270 0.7458 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4316 0.0276 -0.3068 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.2201 -0.3089 -1.5777 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3081 -1.3023 -1.3463 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2114 -0.9101 -0.2009 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.4117 -0.7591 1.0775 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9444 0.2105 -0.5383 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7522 1.4918 -0.0316 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1155 0.7072 1.2876 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1118 2.1399 -1.8356 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4709 1.6025 -2.1679 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8136 2.8647 -0.9004 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2549 1.2931 0.6682 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9006 -0.2283 -1.4936 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2480 0.6832 1.3741 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0811 -0.8038 -0.6535 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8900 -1.0074 2.3977 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2125 -2.1222 1.1895 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0160 -1.8985 1.2280 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6811 1.1824 1.5881 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7921 1.6844 -1.1495 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4015 2.8523 0.0976 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5497 2.0822 -1.0719 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3129 -0.3620 -0.4655 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9721 1.1344 0.3986 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5395 -0.3440 1.3070 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2151 -0.6269 -1.5448 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0196 -1.0991 1.3560 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9308 -2.2071 -0.1087 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0046 -3.0190 0.7104 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2131 -1.5587 1.8143 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6304 -1.5668 -1.2288 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9018 0.7997 -2.0593 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4190 2.1542 -0.8918 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7864 2.1271 -0.8371 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0884 1.4440 0.6635 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8421 -0.3084 -1.6866 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1347 -2.5163 1.5933 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6539 -2.2992 2.1668 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6557 0.5884 -2.0570 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5191 -0.7377 -2.3408 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9477 -1.2993 -2.2601 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9375 -2.3439 -1.2474 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9627 -1.7226 -0.0380 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6348 0.2287 1.5043 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7040 -1.5517 1.8050 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8882 0.3872 -1.5233 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0604 1.8711 0.7142 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7822 1.5980 0.3599 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7779 2.0830 -0.9934 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1875 1.8171 1.2837 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8140 0.4578 1.8226 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9498 0.3369 1.9182 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 5 7 1 0 7 8 1 0 7 9 1 0 2 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 25 27 1 0 22 28 1 1 14 29 1 1 14 10 1 0 18 13 1 0 22 17 1 0 26 21 1 0 1 30 1 0 1 31 1 0 1 32 1 0 2 33 1 1 3 34 1 0 4 35 1 0 5 36 1 6 6 37 1 0 6 38 1 0 6 39 1 0 7 40 1 0 8 41 1 0 8 42 1 0 8 43 1 0 9 44 1 0 9 45 1 0 9 46 1 0 10 47 1 6 11 48 1 0 11 49 1 0 12 50 1 0 12 51 1 0 13 52 1 6 15 53 1 0 15 54 1 0 16 55 1 0 16 56 1 0 17 57 1 6 19 58 1 0 20 59 1 0 23 60 1 0 23 61 1 0 24 62 1 0 24 63 1 0 25 64 1 1 26 65 1 0 26 66 1 0 27 67 1 0 28 68 1 0 28 69 1 0 28 70 1 0 29 71 1 0 29 72 1 0 29 73 1 0 M END

Standard InCHIKey	DNVPQKQSNYMLRS-APGDWVJJSA-N
Standard InCHI	InChI=1S/C28H44O/c1-18(2)19(3)7-8-20(4)24-11-12-25-23-10-9-21-17-22(29)13-15-27(21,5)26(23)14-16-28(24,25)6/h7-10,18-20,22,24-26,29H,11-17H2,1-6H3/b8-7+/t19-,20+,22-,24+,25-,26-,27-,28+/m0/s1
SMILES	C[C@H](/C=C/[C@H](C)C(C)C)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3C2=CC=C4[C@@]3(CC[C@@H](C4)O)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	396.34	Volume:	459.499 ? Van der Waals volume.
Dense:	0.863	LogP:	5.44 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.13 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.125 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	21.0
TPSA:	20.23 ? Topological Polar Surface Area.	H-Bond Acceptor:	1.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	1.0

MedChem Properties

QED Drug-Likeness Score:	0.493	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.631	Fsp³:	0.786
MCE-18:	68.04 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.986	Fluc inhibitor:	0.135 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.619	Promiscuous compounds:	0.164

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.261	MDCK Permeability:	-4.932
Pgp-inhibitor:	0.097	Pgp-substrate:	0.001
PAMPA:	0.03 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.0
20% Bioavailability (F20%):	0.199	30% Bioavailability (F30%):	0.784
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.003
Plasma Protein Binding (PPB):	98.489%	Volume Distribution (VD):	-0.081
Fu:	1.177% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.86
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.051
CYP2C19-inhibitor:	0.007	CYP2C19-substrate:	0.026
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.26
CYP2D6-inhibitor:	0.079	CYP2D6-substrate:	0.947
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.942 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

13.58

Half-life (T1/2):

0.735

ADMET: Toxicity

hERG Blockers:	0.28	hERG Blockers (10um):	0.42
Human Hepatotoxicity (H-HT):	0.74	Drug-induced Liver Injury (DILI):	0.579
AMES Toxicity:	0.165	Rat Oral Acute Toxicity:	0.208
Maximum Recommended Daily Dose:	0.79	Skin Sensitization:	0.763
Carcinogencity:	0.687	Eye Corrosion:	0.001
Eye Irritation:	0.594	Respiratory Toxicity:	0.9
Drug-induced Neurotoxicity:	0.215	Ototoxicity:	0.8
Hematotoxicity:	0.581	Drug-induced Nephrotoxicity:	0.601
Genotoxicity:	0.069	RPMI-8226 Immunitoxicity:	0.234
A549 Cytotoxicity:	0.699	Hek293 Cytotoxicity:	0.633
BCF:	3.27 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.86 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.82 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.872 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO64743	Cercis alata + Fusarium sp. symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[ 30294556]
NPO64773	Bauhinia guianensis + Aspergillus sp. symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[ 33493866]
NPO64773	Bauhinia guianensis + Aspergillus sp. symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[ 33671272]
NPO64773	Bauhinia guianensis + Aspergillus sp. symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	DOI[10.1002/cbdv.200800353]
NPO64873	Astragalus membranaceus + Fusarium sp. symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	DOI[10.1007/s10600-015-1532-0]
NPO64773	Bauhinia guianensis + Aspergillus sp. symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	DOI[10.1007/s10600-015-1532-0]
NPO64773	Bauhinia guianensis + Aspergillus sp. symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	DOI[10.1016/j.ram.2016.04.002]
NPO65010	Xylaria allantoidea SWUF76+Xylaria cf. cubensis PK108 coculture	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[27868429]
NPO41573	two Aspergillus sp. strains	Strain	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[31953204]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
Ratio	2
CI50	2
Inhibition	2
Activity	22
IC50	6

Activity Type	# Activity
Cell line	6
Organism	18
Unchecked	4
Individual protein	6

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	26.56	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	-0.43	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT668	Individual protein	P-glycoprotein 1	Homo sapiens	Ratio	=	1.053	n.a.	PMID[35293752]
NPT668	Individual protein	P-glycoprotein 1	Homo sapiens	CI50	=	1.03	n.a.	PMID[35293752]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2641	Cell line	COLO 320	Homo sapiens	IC50	=	6500.0	nM	PMID[35293752]
NPT171	Cell line	MRC5	Homo sapiens	IC50	=	500.0	nM	PMID[35293752]
NPT407	Cell line	COLO 205	Homo sapiens	IC50	=	4900.0	nM	PMID[35293752]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Activity	n.a.	n.a.	n.a.	PMID[35293752]
NPT28438	Unchecked	Unchecked	n.a.	Activity	n.a.	n.a.	n.a.	PMID[33949869]
NPT2242	Organism	Penicillium chrysogenum	Penicillium chrysogenum	Activity	n.a.	n.a.	n.a.	PMID[36040034]
NPT20	Organism	Candida albicans	Candida albicans	Activity	n.a.	n.a.	n.a.	PMID[36040034]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	Activity	n.a.	n.a.	n.a.	PMID[36040034]
NPT29026	Organism	Sporobolomyces salmonicolor	Sporobolomyces salmonicolor	Activity	n.a.	n.a.	n.a.	PMID[36040034]
NPT19	Organism	Escherichia coli	Escherichia coli	Activity	n.a.	n.a.	n.a.	PMID[35293752]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	Activity	n.a.	n.a.	n.a.	PMID[35293752]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	Activity	n.a.	n.a.	n.a.	PMID[36040034]
NPT28466	Organism	Mycolicibacterium vaccae	Mycolicibacterium vaccae	Activity	n.a.	n.a.	n.a.	PMID[36040034]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	Activity	n.a.	n.a.	n.a.	PMID[36040034]
NPT19	Organism	Escherichia coli	Escherichia coli	Activity	n.a.	n.a.	n.a.	PMID[36040034]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	Activity	n.a.	n.a.	n.a.	PMID[36040034]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC491013 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	23177
0.1-0.2	24037
0.2-0.3	2379
0.3-0.4	179
0.4-0.5	64
0.5-0.6	18
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC307965
1.0	High Similarity	NPC18603
0.7115	Intermediate Similarity	NPC183927
0.5789	Remote Similarity	NPC204188
0.5789	Remote Similarity	NPC80561
0.5789	Remote Similarity	NPC329596
0.5758	Remote Similarity	NPC267510
0.5714	Remote Similarity	NPC134330
0.5614	Remote Similarity	NPC611620
0.5345	Remote Similarity	NPC154330
0.5333	Remote Similarity	NPC49422
0.5333	Remote Similarity	NPC9161
0.5312	Remote Similarity	NPC472220
0.5312	Remote Similarity	NPC97884
0.5254	Remote Similarity	NPC129165
0.5254	Remote Similarity	NPC113733
0.5246	Remote Similarity	NPC291484
0.5167	Remote Similarity	NPC234193
0.5079	Remote Similarity	NPC118648
0.5079	Remote Similarity	NPC475022
0.5079	Remote Similarity	NPC600021

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC491013 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7577
0.1-0.2	1413
0.2-0.3	131
0.3-0.4	17
0.4-0.5	6
0.5-0.6	5
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.5614	Remote Similarity	NPD7150	Approved
0.5614	Remote Similarity	NPD7151	Phase 4
0.5614	Remote Similarity	NPD7152	Approved
0.5333	Remote Similarity	NPD7143	Approved
0.5333	Remote Similarity	NPD7144	Phase 4

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data