NPASS Compound

Natural Product: NPC472631

Natural Product ID	NPC472631
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	UTJACGGIQKDKBW-VIZOYTHASA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3581351
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0003646] 6-prenylated flavans [CHEMONTID:0003507] 6-prenylated flavanones

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 75 0 0 0 0 0 0 0 0999 V2000 8.1870 -3.1982 -1.0625 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6900 -1.9281 -0.6631 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8497 -1.0097 -0.0602 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4985 -1.2675 0.1857 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6806 -0.3501 0.7820 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1975 0.8729 1.1570 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5168 1.1611 0.9322 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3443 0.2172 0.3222 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6982 0.4964 0.0845 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0485 2.3749 1.2993 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2195 3.3335 1.9153 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2442 -0.6150 1.0391 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8686 -1.8433 0.2310 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4207 -1.9229 0.0014 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8521 -3.0276 -0.0171 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6534 -0.7128 -0.2040 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2075 0.5066 0.1665 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4709 0.4964 0.7148 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4897 1.6642 -0.0233 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2306 1.6612 -0.5721 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3328 0.4698 -0.9440 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3960 -0.6957 -0.7499 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1668 -1.9219 -1.1249 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6692 0.3702 -1.5400 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7225 0.5294 -0.4733 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6895 1.4011 -0.5002 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7059 1.5676 0.4999 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8629 0.6591 1.6423 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3393 -0.7155 1.3936 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7189 -0.7589 0.7477 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6077 -0.3421 -0.5603 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7887 -0.3358 -1.2575 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7368 0.0664 1.4522 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1841 -2.1971 0.7588 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5391 -1.5403 0.6855 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7813 2.3286 -1.7101 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4685 2.8640 -0.7491 O 0 0 0 0 0 0 0 0 0 0 0 0 8.9676 -3.8302 -1.5044 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6834 -3.7254 -0.2197 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3912 -3.0265 -1.8300 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1435 -2.2261 -0.1178 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5696 1.6168 1.6315 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9673 0.5598 -0.8856 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9542 2.9729 2.9156 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2718 3.5067 1.3282 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7284 4.3362 1.9624 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1403 -0.8183 2.1280 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3270 -2.7369 0.6627 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3266 -1.6631 -0.7869 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9644 2.6031 0.2834 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9374 -2.2947 -0.5847 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8196 1.0698 -2.3878 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8197 -0.6440 -1.9561 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5855 -0.1188 0.3712 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7167 1.7339 -0.0153 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5539 2.6152 0.9570 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4993 1.1299 2.4626 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8686 0.5480 2.1944 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4561 -1.2011 2.4238 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5408 0.0241 -2.2977 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2395 -1.3392 -1.3989 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4881 0.3935 -0.7953 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7836 1.1098 1.0589 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6743 0.0228 2.5539 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7438 -0.3807 1.2003 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9077 -2.7299 -0.1848 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7221 -2.7615 1.5986 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2986 -2.2706 0.8828 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5959 -2.4978 0.9103 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7882 2.8108 -1.7587 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0319 3.1186 -1.5737 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6999 1.7386 -2.6322 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1142 3.6966 -0.3252 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 7 10 1 0 10 11 1 0 5 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 2 0 17 18 1 0 17 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 21 24 1 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 30 33 1 0 30 34 1 0 29 35 1 0 26 36 1 0 20 37 1 0 8 3 1 0 18 12 1 0 22 16 1 0 1 38 1 0 1 39 1 0 1 40 1 0 4 41 1 0 6 42 1 0 9 43 1 0 11 44 1 0 11 45 1 0 11 46 1 0 12 47 1 0 13 48 1 0 13 49 1 0 19 50 1 0 23 51 1 0 24 52 1 0 24 53 1 0 25 54 1 0 27 55 1 0 27 56 1 0 28 57 1 0 28 58 1 0 29 59 1 0 32 60 1 0 32 61 1 0 32 62 1 0 33 63 1 0 33 64 1 0 33 65 1 0 34 66 1 0 34 67 1 0 34 68 1 0 35 69 1 0 36 70 1 0 36 71 1 0 36 72 1 0 37 73 1 0 M END

Standard InCHIKey	UTJACGGIQKDKBW-VIZOYTHASA-N
Standard InCHI	InChI=1S/C28H36O9/c1-15(8-10-24(31)28(2,3)36-6)7-9-17-18(29)13-21-25(26(17)32)19(30)14-20(37-21)16-11-22(34-4)27(33)23(12-16)35-5/h7,11-13,20,24,29,31-33H,8-10,14H2,1-6H3/b15-7+
SMILES	COc1cc(cc(c1O)OC)C1CC(=O)c2c(O1)cc(c(c2O)C/C=C(/CCC(C(OC)(C)C)O)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	516.24	Volume:	525.195 ? Van der Waals volume.
Dense:	0.983	LogP:	4.025 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.135 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.149 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	19.0
TPSA:	134.91 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.335	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.002	Fsp³:	0.464
MCE-18:	77.439 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.198	Fluc inhibitor:	0.094 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.349 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.789 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.08	Promiscuous compounds:	0.011

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.2	MDCK Permeability:	-4.825
Pgp-inhibitor:	0.998	Pgp-substrate:	0.008
PAMPA:	0.008 ? 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):	0.113
20% Bioavailability (F20%):	0.022	30% Bioavailability (F30%):	0.741
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.736
Plasma Protein Binding (PPB):	95.792%	Volume Distribution (VD):	0.065
Fu:	3.473% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.996
BSEP inhibitor:	0.991

ADMET: Metabolism

CYP1A2-inhibitor:	0.143	CYP1A2-substrate:	0.998
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.998
CYP2C9-inhibitor:	0.925	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.056	CYP2D6-substrate:	0.962
CYP3A4-inhibitor:	0.953	CYP3A4-substrate:	0.06
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.998
HLM stability:	0.968 ? 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):

5.361

Half-life (T1/2):

1.336

ADMET: Toxicity

hERG Blockers:	0.077	hERG Blockers (10um):	0.604
Human Hepatotoxicity (H-HT):	0.765	Drug-induced Liver Injury (DILI):	0.735
AMES Toxicity:	0.458	Rat Oral Acute Toxicity:	0.659
Maximum Recommended Daily Dose:	0.771	Skin Sensitization:	0.583
Carcinogencity:	0.444	Eye Corrosion:	0.0
Eye Irritation:	0.435	Respiratory Toxicity:	0.956
Drug-induced Neurotoxicity:	0.221	Ototoxicity:	0.663
Hematotoxicity:	0.37	Drug-induced Nephrotoxicity:	0.787
Genotoxicity:	0.973	RPMI-8226 Immunitoxicity:	0.306
A549 Cytotoxicity:	0.725	Hek293 Cytotoxicity:	0.824
BCF:	1.229 ? 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:	3.858 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.688 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.75 ? 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
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	fruits	n.a.	n.a.	PMID[17625893]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[18293924]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20192247]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	fruit	n.a.	PMID[21319773]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	fruits	n.a.	n.a.	PMID[22445674]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	fruits	n.a.	n.a.	PMID[23623680]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	fruits	n.a.	n.a.	PMID[25735399]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[28322565]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[28968119]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

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
IC50	1

Activity Type	# Activity
Cell line	1

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
NPT1970	Cell line	THP-1	Homo sapiens	IC50	>	10000.0	nM	PMID[19778087]

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 NPC472631 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	10445
0.1-0.2	34565
0.2-0.3	4392
0.3-0.4	368
0.4-0.5	46
0.5-0.6	19
0.6-0.7	16
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8429	Intermediate Similarity	NPC472630
0.8356	Intermediate Similarity	NPC472634
0.7917	Intermediate Similarity	NPC472628
0.7778	Intermediate Similarity	NPC488558
0.7746	Intermediate Similarity	NPC470328
0.7746	Intermediate Similarity	NPC209614
0.7051	Intermediate Similarity	NPC474055
0.6753	Remote Similarity	NPC488554
0.65	Remote Similarity	NPC488555
0.65	Remote Similarity	NPC484418
0.6494	Remote Similarity	NPC472627
0.6456	Remote Similarity	NPC45849
0.6456	Remote Similarity	NPC195796
0.641	Remote Similarity	NPC321779
0.6267	Remote Similarity	NPC35038
0.625	Remote Similarity	NPC488557
0.6234	Remote Similarity	NPC64915
0.6203	Remote Similarity	NPC226025
0.6203	Remote Similarity	NPC278778
0.6173	Remote Similarity	NPC27337
0.6154	Remote Similarity	NPC164272
0.6154	Remote Similarity	NPC470327
0.6049	Remote Similarity	NPC472626
0.5949	Remote Similarity	NPC488556
0.5897	Remote Similarity	NPC290133
0.5897	Remote Similarity	NPC228504
0.5875	Remote Similarity	NPC261063
0.5823	Remote Similarity	NPC213896
0.5753	Remote Similarity	NPC1089
0.5714	Remote Similarity	NPC223787
0.5679	Remote Similarity	NPC185276
0.5647	Remote Similarity	NPC471499
0.561	Remote Similarity	NPC298692
0.5526	Remote Similarity	NPC125855
0.5412	Remote Similarity	NPC472598
0.5349	Remote Similarity	NPC287328
0.5128	Remote Similarity	NPC223500
0.5128	Remote Similarity	NPC166689
0.5116	Remote Similarity	NPC282009
0.5116	Remote Similarity	NPC210459
0.5111	Remote Similarity	NPC472635
0.5059	Remote Similarity	NPC470326

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC472631 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3320
0.1-0.2	5736
0.2-0.3	89
0.3-0.4	5
0.4-0.5	0
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