NPASS Compound

Natural Product: NPC471066

Natural Product ID	NPC471066
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(5S)-5-Hydroxy-1,7-Bis-(4-Hydroxyphenyl)-3-Heptanone-5-O-Beta-D-Apiofuranosyl-(1->6)-Beta-D-Glucopyranoside
IUPAC Name	(5S)-5-[(2R,3R,4S,5S,6R)-6-[[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxymethyl]-3,4,5-trihydroxyoxan-2-yl]oxy-1,7-bis(4-hydroxyphenyl)heptan-3-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2346810
PubChem CID	71720155
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002650] Diarylheptanoids [CHEMONTID:0002651] Linear diarylheptanoids [CHEMONTID:0000356] Curcuminoids

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 83 86 0 0 0 0 0 0 0 0999 V2000 -2.4410 -2.3370 3.9281 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1992 -3.0579 4.8450 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8150 -4.2207 4.4445 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6578 -4.6443 3.1199 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9102 -3.9360 2.2117 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2888 -2.7554 2.6290 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4877 -2.0147 1.6006 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4133 -1.0506 0.8802 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7098 -0.2727 -0.1821 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6720 0.6694 -0.8438 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8306 0.0739 -1.5075 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7618 -0.4233 -2.6485 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1470 0.0372 -0.8544 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7304 1.4199 -0.6294 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9105 2.1974 -1.8675 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0881 2.1144 -2.5520 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2616 2.8388 -3.7003 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2662 3.6505 -4.1761 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0512 3.7492 -3.4896 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9046 3.0147 -2.3449 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4623 4.3753 -5.3394 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6648 0.5044 0.2863 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5581 0.1885 -0.2708 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1355 1.2663 -1.1241 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0746 0.5655 -2.1187 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6854 -0.5843 -1.3719 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7782 -0.2935 0.1184 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4867 -0.2326 0.6556 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5072 -1.4426 0.7618 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8349 -1.5686 0.4440 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6021 -0.4990 0.8907 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4747 0.0112 -0.2093 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5972 0.6977 0.5688 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5079 0.0404 1.9058 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5445 -0.9314 1.8437 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2507 1.0869 2.9529 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3173 2.0059 2.8938 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2750 2.0522 0.6377 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0564 -1.0131 -0.9426 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9442 -0.8225 -1.8619 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9768 1.4311 -2.6793 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8821 2.2184 -0.4734 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5869 -4.9899 5.3065 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9525 -1.4128 4.2540 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3263 -2.7387 5.8728 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1333 -5.5640 2.7646 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7801 -4.2601 1.1715 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0068 -2.7348 0.9358 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7265 -1.4309 2.1536 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9308 -0.4397 1.6430 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2074 -1.7155 0.4280 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3821 -1.0098 -0.9472 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0078 1.4721 -0.1465 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1305 1.2586 -1.6567 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1800 -0.4782 0.1157 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9061 -0.5107 -1.4879 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7306 1.2362 -0.1369 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1318 1.9659 0.1294 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8777 1.4865 -2.1983 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2154 2.7471 -4.2200 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2671 4.4006 -3.8837 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9589 3.0820 -1.7951 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4960 5.3951 -5.2729 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3543 -0.6920 -0.9540 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3495 1.7411 -1.7900 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4065 0.1006 -2.9043 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1041 -1.5406 -1.5332 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3741 0.6148 0.2474 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9562 -2.4170 0.6111 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4670 -1.3106 1.8879 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0285 0.2850 1.3780 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9566 0.7451 -0.8676 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5728 0.5577 0.0606 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5321 -0.3708 2.1336 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3403 1.7015 2.7508 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2510 0.6817 3.9887 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1518 2.8269 3.3855 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7218 2.5809 -0.0750 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0786 -1.8157 -0.3591 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2122 -1.7749 -1.8969 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2190 1.0434 -3.5829 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4594 2.6540 0.2848 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4168 -5.4790 4.9448 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 11 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 18 21 1 0 9 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 33 38 1 0 32 39 1 0 26 40 1 0 25 41 1 0 24 42 1 0 3 43 1 0 6 1 1 0 20 15 1 0 28 23 1 0 35 31 1 0 1 44 1 0 2 45 1 0 4 46 1 0 5 47 1 0 7 48 1 0 7 49 1 0 8 50 1 0 8 51 1 0 9 52 1 0 10 53 1 0 10 54 1 0 13 55 1 0 13 56 1 0 14 57 1 0 14 58 1 0 16 59 1 0 17 60 1 0 19 61 1 0 20 62 1 0 21 63 1 0 23 64 1 0 24 65 1 0 25 66 1 0 26 67 1 0 27 68 1 0 29 69 1 0 29 70 1 0 31 71 1 0 32 72 1 0 33 73 1 0 34 74 1 0 36 75 1 0 36 76 1 0 37 77 1 0 38 78 1 0 39 79 1 0 40 80 1 0 41 81 1 0 42 82 1 0 43 83 1 0 M END

Standard InCHIKey	UGYZLORFQGTFRN-SHYGZIMPSA-N
Standard InCHI	InChI=1S/C30H40O13/c31-14-22-24(35)27(38)29(42-22)40-15-23-25(36)26(37)28(39)30(43-23)41-21(12-6-17-3-9-19(33)10-4-17)13-20(34)11-5-16-1-7-18(32)8-2-16/h1-4,7-10,21-33,35-39H,5-6,11-15H2/t21-,22+,23+,24+,25+,26-,27+,28+,29+,30+/m0/s1
SMILES	C1=CC(=CC=C1CCC(CC(=O)CCC2=CC=C(C=C2)O)OC3C(C(C(C(O3)COC4C(C(C(O4)CO)O)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	608.25	Volume:	589.028 ? Van der Waals volume.
Dense:	1.033	LogP:	-0.119 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.546 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.715 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	14.0	Rigid Bonds:	24.0
TPSA:	215.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	8.0	Rings:	4.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.133	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.584	Fsp³:	0.567
MCE-18:	91.34 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.024	Fluc inhibitor:	0.022 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.011 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.362 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.298	Promiscuous compounds:	0.115

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.318	MDCK Permeability:	-5.079
Pgp-inhibitor:	0.001	Pgp-substrate:	0.973
PAMPA:	0.999 ? 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):	0.02
20% Bioavailability (F20%):	0.277	30% Bioavailability (F30%):	0.997
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.082
Plasma Protein Binding (PPB):	75.249%	Volume Distribution (VD):	-0.287
Fu:	23.928% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.003
OATP1B3 inhibitor:	0.675	BCRP inhibitor:	0.019
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.997	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.725	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.05	CYP2D6-substrate:	0.461
CYP3A4-inhibitor:	0.019	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.324
HLM stability:	0.248 ? 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):

2.229

Half-life (T1/2):

2.492

ADMET: Toxicity

hERG Blockers:	0.222	hERG Blockers (10um):	0.723
Human Hepatotoxicity (H-HT):	0.518	Drug-induced Liver Injury (DILI):	0.063
AMES Toxicity:	0.539	Rat Oral Acute Toxicity:	0.093
Maximum Recommended Daily Dose:	0.373	Skin Sensitization:	0.254
Carcinogencity:	0.055	Eye Corrosion:	0.0
Eye Irritation:	0.018	Respiratory Toxicity:	0.006
Drug-induced Neurotoxicity:	0.691	Ototoxicity:	0.985
Hematotoxicity:	0.029	Drug-induced Nephrotoxicity:	0.258
Genotoxicity:	0.088	RPMI-8226 Immunitoxicity:	0.042
A549 Cytotoxicity:	0.068	Hek293 Cytotoxicity:	0.931
BCF:	0.583 ? 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:	3.088 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.009 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.021 ? 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
NPO32876	alnus hirsuta f. sibirica	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23465614]
NPO32876	alnus hirsuta f. sibirica	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
Activity	3

Activity Type	# Activity
Cell line	3

Molecular-level activity

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

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	24.8	%	PMID[21377877]
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	34.6	%	DOI[10.6019/CHEMBL1201861]
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	88.4	%	PMID[16472241]

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 NPC471066 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	12055
0.1-0.2	31794
0.2-0.3	5108
0.3-0.4	761
0.4-0.5	106
0.5-0.6	12
0.6-0.7	13
0.7-0.8	0
0.8-0.85	4
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8125	Intermediate Similarity	NPC471095
0.803	Intermediate Similarity	NPC164172
0.8	Intermediate Similarity	NPC17968
0.8	Intermediate Similarity	NPC469705
0.7903	Intermediate Similarity	NPC282409
0.7903	Intermediate Similarity	NPC469702
0.7727	Intermediate Similarity	NPC471067
0.7258	Intermediate Similarity	NPC158673
0.6667	Remote Similarity	NPC293686
0.6618	Remote Similarity	NPC158325
0.6618	Remote Similarity	NPC193018
0.6522	Remote Similarity	NPC476407
0.6429	Remote Similarity	NPC476448
0.6429	Remote Similarity	NPC469548
0.6429	Remote Similarity	NPC476445
0.6351	Remote Similarity	NPC232454
0.6351	Remote Similarity	NPC470907
0.6351	Remote Similarity	NPC178449
0.6133	Remote Similarity	NPC469696
0.6029	Remote Similarity	NPC103398
0.6029	Remote Similarity	NPC608691
0.5882	Remote Similarity	NPC160854
0.5882	Remote Similarity	NPC201402
0.5882	Remote Similarity	NPC469704
0.5882	Remote Similarity	NPC469703
0.5781	Remote Similarity	NPC148055
0.5753	Remote Similarity	NPC180171
0.5405	Remote Similarity	NPC79715
0.5405	Remote Similarity	NPC108659
0.5375	Remote Similarity	NPC469549
0.5169	Remote Similarity	NPC212808
0.5152	Remote Similarity	NPC157338
0.507	Remote Similarity	NPC57751

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC471066 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3946
0.1-0.2	4986
0.2-0.3	212
0.3-0.4	5
0.4-0.5	1
0.5-0.6	0
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
		NPD

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