NPASS Compound

Natural Product: NPC470769

Natural Product ID	NPC470769
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Buddlenol A
IUPAC Name	(E)-3-[(2R,3S)-2-[4-[1,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)propan-2-yl]oxy-3,5-dimethoxyphenyl]-3-(hydroxymethyl)-7-methoxy-2,3-dihydro-1-benzofuran-5-yl]prop-2-enal
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL221879
PubChem CID	44421295
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0003405] 2-arylbenzofuran flavonoids

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 76 79 0 0 0 0 0 0 0 0999 V2000 9.5965 2.2718 -3.9866 O 0 0 0 0 0 0 0 0 0 0 0 0 9.4696 2.3255 -2.7425 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2681 1.7736 -2.1391 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0479 1.7857 -0.8366 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8628 1.2464 -0.1866 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8210 0.6536 -0.8560 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7028 0.1490 -0.1987 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4465 -0.5321 -0.6542 C 0 0 1 0 0 0 0 0 0 0 0 0 3.8801 -1.7016 -1.5215 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6707 -2.5774 -0.7920 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8922 -1.0995 0.6311 C 0 0 1 0 0 0 0 0 0 0 0 0 3.4728 -0.2985 1.6454 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6554 0.2567 1.1758 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6815 0.8465 1.8960 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7548 1.3231 1.1846 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5965 0.9360 3.2787 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6599 1.5426 3.9735 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4161 -0.9485 0.7376 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8220 0.2829 0.9035 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5469 0.4753 1.0089 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0727 1.7510 1.1775 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1694 2.8348 1.2370 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3865 -0.6453 0.9433 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8196 -1.8904 0.7781 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5705 -2.0353 0.6765 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5875 -3.0339 0.7073 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9583 -4.2832 0.5386 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7260 -0.4513 1.0451 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6904 -0.2667 0.0646 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8819 -1.1490 0.2577 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9624 -0.8732 -0.7181 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9282 -1.3392 -2.0115 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9545 -1.0694 -2.9130 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0370 -0.3210 -2.5214 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0739 0.1466 -1.2279 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0506 -0.1240 -0.3337 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1792 0.9038 -0.8485 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.2440 1.4005 0.4822 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0809 -0.0402 -3.4197 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5060 -2.4816 0.2064 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1185 1.1974 -0.0790 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6277 1.7254 1.0799 O 0 0 0 0 0 0 0 0 0 0 0 0 10.2485 2.7749 -2.1656 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5147 1.3314 -2.7714 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8256 2.2368 -0.2396 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8475 0.5643 -1.9281 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7646 0.1347 -1.1774 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5171 -1.3163 -2.3616 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0090 -2.2093 -1.9922 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3999 -2.9597 -1.3327 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1761 -2.1409 0.8022 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5749 1.7917 1.7313 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6253 1.0205 3.8223 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4903 1.5613 5.0699 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7351 2.5817 3.6257 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4719 1.1573 0.9545 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5604 2.6336 2.0522 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6852 3.8032 1.3427 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4476 2.8526 0.2928 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0177 -3.0217 0.5455 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3648 -4.3161 -0.3978 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2386 -4.4991 1.3702 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6862 -5.1162 0.5568 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2479 -0.5091 -0.9443 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2729 -0.9889 1.2999 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1090 -1.9265 -2.3690 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9300 -1.4348 -3.9305 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0988 0.2573 0.6909 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2277 1.8464 0.6924 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4062 2.1352 0.6472 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0685 0.5648 1.1775 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0143 0.0279 -2.9854 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1649 -3.0578 0.7000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9113 1.1873 -0.8763 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2371 1.7671 -0.4006 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2481 2.5996 1.3092 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 8 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 1 0 11 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 1 0 20 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 1 0 23 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 35 37 1 0 37 38 1 0 34 39 1 0 30 40 1 0 29 41 1 0 41 42 1 0 15 5 1 0 25 18 1 0 36 31 1 0 13 7 2 0 2 43 1 0 3 44 1 0 4 45 1 0 6 46 1 0 8 47 1 6 9 48 1 0 9 49 1 0 10 50 1 0 11 51 1 1 15 52 1 0 17 53 1 0 17 54 1 0 17 55 1 0 19 56 1 0 22 57 1 0 22 58 1 0 22 59 1 0 25 60 1 0 27 61 1 0 27 62 1 0 27 63 1 0 29 64 1 0 30 65 1 0 32 66 1 0 33 67 1 0 36 68 1 0 38 69 1 0 38 70 1 0 38 71 1 0 39 72 1 0 40 73 1 0 41 74 1 0 41 75 1 0 42 76 1 0 M END

Standard InCHIKey	UYNCCRHOWNHDMT-WWZDYYMFSA-N
Standard InCHI	InChI=1S/C31H34O11/c1-37-23-12-18(7-8-22(23)35)28(36)27(16-34)41-31-25(39-3)13-19(14-26(31)40-4)29-21(15-33)20-10-17(6-5-9-32)11-24(38-2)30(20)42-29/h5-14,21,27-29,33-36H,15-16H2,1-4H3/b6-5+/t21-,27?,28?,29+/m1/s1
SMILES	O=C/C=C/c1cc2[C@@H](CO)[C@@H](Oc2c(c1)OC)c1cc(OC)c(c(c1)OC)OC(C(c1ccc(c(c1)OC)O)O)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	582.21	Volume:	578.198 ? Van der Waals volume.
Dense:	1.007	LogP:	2.047 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.387 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.072 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	13.0	Rigid Bonds:	24.0
TPSA:	153.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	4.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.173	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.258	Fsp³:	0.323
MCE-18:	83.634 ? 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:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.752	Fluc inhibitor:	0.506 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.097 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.679 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.219	Promiscuous compounds:	0.113

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.361	MDCK Permeability:	-5.055
Pgp-inhibitor:	0.028	Pgp-substrate:	0.027
PAMPA:	0.381 ? 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):	0.01
20% Bioavailability (F20%):	0.393	30% Bioavailability (F30%):	0.524
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.525
Plasma Protein Binding (PPB):	74.55%	Volume Distribution (VD):	-0.206
Fu:	26.785% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.898
BSEP inhibitor:	0.874

ADMET: Metabolism

CYP1A2-inhibitor:	0.121	CYP1A2-substrate:	0.005
CYP2C19-inhibitor:	0.978	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.218	CYP2C9-substrate:	0.477
CYP2D6-inhibitor:	0.198	CYP2D6-substrate:	0.428
CYP3A4-inhibitor:	0.46	CYP3A4-substrate:	0.989
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.025 ? 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):

6.764

Half-life (T1/2):

1.735

ADMET: Toxicity

hERG Blockers:	0.108	hERG Blockers (10um):	0.293
Human Hepatotoxicity (H-HT):	0.854	Drug-induced Liver Injury (DILI):	0.611
AMES Toxicity:	0.604	Rat Oral Acute Toxicity:	0.21
Maximum Recommended Daily Dose:	0.718	Skin Sensitization:	0.63
Carcinogencity:	0.619	Eye Corrosion:	0.0
Eye Irritation:	0.015	Respiratory Toxicity:	0.274
Drug-induced Neurotoxicity:	0.588	Ototoxicity:	0.951
Hematotoxicity:	0.355	Drug-induced Nephrotoxicity:	0.908
Genotoxicity:	0.881	RPMI-8226 Immunitoxicity:	0.306
A549 Cytotoxicity:	0.287	Hek293 Cytotoxicity:	0.513
BCF:	0.995 ? 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:	3.628 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.402 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.626 ? 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
NPO14922	Tarenna attenuata	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16792422]
NPO14922	Tarenna attenuata	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17343407]
NPO14922	Tarenna attenuata	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14922	Tarenna attenuata	Species	Rubiaceae	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
Activity	4
IC50	2

Activity Type	# Activity
Cell line	4
Others	1
Non-molecular	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
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	56.9	%	PubChem BioAssay data set
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	56.8	%	PubChem BioAssay data set
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	62.6	%	PMID[3655802]
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	64.8	%	PMID[25554367]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	15280.0	nM	PMID[26774654]
NPT1	Others	Radical scavenging activity	n.a.	IC50	=	147000.0	nM	PMID[19848432]

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 NPC470769 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	24799
0.1-0.2	22022
0.2-0.3	2715
0.3-0.4	211
0.4-0.5	60
0.5-0.6	30
0.6-0.7	9
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9718	High Similarity	NPC470828
0.92	High Similarity	NPC470827
0.863	High Similarity	NPC260397
0.76	Intermediate Similarity	NPC43065
0.7183	Intermediate Similarity	NPC284881
0.7183	Intermediate Similarity	NPC93433
0.7183	Intermediate Similarity	NPC474444
0.7143	Intermediate Similarity	NPC267291
0.6559	Remote Similarity	NPC485396
0.6559	Remote Similarity	NPC485394
0.6559	Remote Similarity	NPC485395
0.6438	Remote Similarity	NPC473408
0.6133	Remote Similarity	NPC476387
0.6133	Remote Similarity	NPC237594
0.6133	Remote Similarity	NPC119060
0.6	Remote Similarity	NPC156502
0.6	Remote Similarity	NPC10737
0.5946	Remote Similarity	NPC7903
0.5946	Remote Similarity	NPC160991
0.5897	Remote Similarity	NPC206413
0.5897	Remote Similarity	NPC482649
0.5897	Remote Similarity	NPC149003
0.5897	Remote Similarity	NPC482647
0.5897	Remote Similarity	NPC482648
0.5897	Remote Similarity	NPC482651
0.5897	Remote Similarity	NPC194244
0.5897	Remote Similarity	NPC482650
0.5714	Remote Similarity	NPC181615
0.5696	Remote Similarity	NPC253878
0.5696	Remote Similarity	NPC471414
0.5556	Remote Similarity	NPC163898
0.5443	Remote Similarity	NPC224876
0.5395	Remote Similarity	NPC87725
0.5395	Remote Similarity	NPC263261
0.5301	Remote Similarity	NPC480707
0.5195	Remote Similarity	NPC300757
0.519	Remote Similarity	NPC147821
0.519	Remote Similarity	NPC319625
0.519	Remote Similarity	NPC183181
0.519	Remote Similarity	NPC41706
0.5185	Remote Similarity	NPC470098
0.5185	Remote Similarity	NPC473266
0.5181	Remote Similarity	NPC470097
0.5135	Remote Similarity	NPC310854
0.5128	Remote Similarity	NPC26394
0.5125	Remote Similarity	NPC472961
0.5125	Remote Similarity	NPC472962

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470769 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4503
0.1-0.2	4567
0.2-0.3	76
0.3-0.4	4
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