NPASS Compound

Natural Product: NPC87630

Natural Product ID	NPC87630
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Intrapetacin B
IUPAC Name	[(1S,3R,5S,6aS,7R,8R,10S,10aS)-1,3-diacetyloxy-10-hydroxy-7,8-dimethyl-7-(3-methylidenepent-4-enyl)-1,3,5,6,6a,8,9,10-octahydrobenzo[d][2]benzofuran-5-yl] 4-hydroxybenzoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL514973
PubChem CID	44584774
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0001757] Colensane and clerodane diterpenoids

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 78 81 0 0 0 0 0 0 0 0999 V2000 -5.8326 0.4947 0.0640 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8675 1.6143 0.7464 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8633 2.6267 0.5885 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0211 3.7492 1.3260 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6938 2.5208 -0.3282 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7143 1.5652 0.2314 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4276 1.3514 -0.4729 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7046 2.7155 -0.5324 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5805 0.9444 -1.8865 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2513 1.8402 -2.8328 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1649 -0.4285 -2.0173 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1735 -1.3888 -1.4234 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7339 -1.0490 -0.0371 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5035 -1.8894 0.2231 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6724 -1.4149 0.5227 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9618 0.0218 0.6566 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8811 0.8646 0.0885 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5417 0.3603 0.2882 C 0 0 1 0 0 0 0 0 0 0 0 0 3.1710 0.3184 -0.0524 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3065 0.8178 0.5402 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2856 1.0250 1.7668 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4688 1.0762 -0.2994 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6242 1.5779 0.2755 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7502 1.8368 -0.4912 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7369 1.5969 -1.8487 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5860 1.0982 -2.4148 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4633 0.8396 -1.6535 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8793 1.8651 -2.5957 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0309 -3.2685 0.0898 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6886 -4.1958 0.8973 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3720 -5.2893 0.4018 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3568 -5.4759 -0.8422 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1148 -6.2474 1.2312 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3559 -3.1986 0.5129 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6246 -1.8658 0.8805 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3993 -1.6365 2.2330 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3184 -1.1847 3.1502 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4817 -0.9489 2.7544 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9138 -0.9864 4.5869 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8583 -2.6300 -1.4963 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6238 -0.2724 0.2094 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1132 0.2035 -0.6770 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7107 1.7317 1.4456 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8767 3.7960 1.9661 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3003 4.5482 1.2507 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1639 2.0846 -1.2690 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3408 3.5442 -0.4999 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4090 2.0185 1.2521 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2325 0.6481 0.5399 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3806 3.4667 -0.9851 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5248 3.1064 0.4855 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1801 2.6876 -1.1905 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4997 0.8065 -2.2628 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3889 2.8864 -2.5809 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6026 1.8868 -3.7764 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1887 1.3596 -3.2653 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2114 -0.6569 -3.1170 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1405 -0.6024 -1.6078 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3293 -1.4814 -2.1295 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4805 -2.1375 0.6821 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2066 0.2969 1.7264 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0280 1.8649 0.5466 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1124 0.9234 -1.0206 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7593 0.5192 1.3451 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6432 1.7683 1.3341 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6292 2.2310 0.0184 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5725 0.9096 -3.4747 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5446 0.4429 -2.1016 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7333 2.1738 -2.1766 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1045 -3.6420 -0.9408 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5363 -5.8003 2.1605 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4203 -7.0957 1.4720 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9568 -6.6624 0.6439 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6737 -1.6250 0.6192 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4486 -0.0992 5.0152 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2314 -1.9083 5.1126 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8145 -0.8644 4.6602 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4526 -2.6794 -2.2609 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 3 5 1 0 5 6 1 0 7 6 1 1 7 8 1 0 7 9 1 0 9 10 1 0 9 11 1 0 11 12 1 0 12 13 1 0 13 14 1 6 14 15 2 0 15 16 1 0 16 17 1 0 17 18 1 0 16 19 1 0 19 20 1 0 20 21 2 0 20 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 25 28 1 0 14 29 1 0 29 30 1 0 30 31 1 0 31 32 2 0 31 33 1 0 29 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 37 38 2 0 37 39 1 0 12 40 1 0 18 7 1 0 27 22 1 0 18 13 1 0 35 13 1 0 1 41 1 0 1 42 1 0 2 43 1 0 4 44 1 0 4 45 1 0 5 46 1 0 5 47 1 0 6 48 1 0 6 49 1 0 8 50 1 0 8 51 1 0 8 52 1 0 9 53 1 6 10 54 1 0 10 55 1 0 10 56 1 0 11 57 1 0 11 58 1 0 12 59 1 6 15 60 1 0 16 61 1 1 17 62 1 0 17 63 1 0 18 64 1 1 23 65 1 0 24 66 1 0 26 67 1 0 27 68 1 0 28 69 1 0 29 70 1 6 33 71 1 0 33 72 1 0 33 73 1 0 35 74 1 6 39 75 1 0 39 76 1 0 39 77 1 0 40 78 1 0 M END

Standard InCHIKey	VVPBNSGOLQBLTJ-VERPJTLHSA-N
Standard InCHI	InChI=1S/C31H38O9/c1-7-17(2)12-13-30(6)18(3)14-26(35)31-24(28(37-19(4)32)40-29(31)38-20(5)33)15-23(16-25(30)31)39-27(36)21-8-10-22(34)11-9-21/h7-11,15,18,23,25-26,28-29,34-35H,1-2,12-14,16H2,3-6H3/t18-,23-,25+,26+,28+,29-,30-,31-/m1/s1
SMILES	C=CC(=C)CC[C@]1(C)[C@H](C)C[C@@H]([C@@]23C(=C[C@H](C[C@@H]12)OC(=O)c1ccc(cc1)O)[C@@H](OC(=O)C)O[C@H]3OC(=O)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	554.25	Volume:	565.89 ? Van der Waals volume.
Dense:	0.979	LogP:	3.17 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.143 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.401 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	26.0
TPSA:	128.59 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.205	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.582	Fsp³:	0.516
MCE-18:	137.191 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.745	Fluc inhibitor:	0.023 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.01 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.053 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.106	Promiscuous compounds:	0.316

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.049	MDCK Permeability:	-4.796
Pgp-inhibitor:	0.996	Pgp-substrate:	0.67
PAMPA:	0.348 ? 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):	0.005
20% Bioavailability (F20%):	1.0	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.968
Plasma Protein Binding (PPB):	95.198%	Volume Distribution (VD):	-0.107
Fu:	4.518% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.99	BCRP inhibitor:	0.906
BSEP inhibitor:	0.977

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.024
CYP2C19-inhibitor:	0.024	CYP2C19-substrate:	0.007
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.01
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.311
CYP3A4-inhibitor:	0.003	CYP3A4-substrate:	0.036
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.947
HLM stability:	0.987 ? 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):

6.853

Half-life (T1/2):

1.352

ADMET: Toxicity

hERG Blockers:	0.054	hERG Blockers (10um):	0.493
Human Hepatotoxicity (H-HT):	0.292	Drug-induced Liver Injury (DILI):	0.533
AMES Toxicity:	0.749	Rat Oral Acute Toxicity:	0.818
Maximum Recommended Daily Dose:	0.966	Skin Sensitization:	0.963
Carcinogencity:	0.652	Eye Corrosion:	0.0
Eye Irritation:	0.171	Respiratory Toxicity:	0.618
Drug-induced Neurotoxicity:	0.623	Ototoxicity:	0.43
Hematotoxicity:	0.237	Drug-induced Nephrotoxicity:	0.659
Genotoxicity:	0.962	RPMI-8226 Immunitoxicity:	0.152
A549 Cytotoxicity:	0.653	Hek293 Cytotoxicity:	0.667
BCF:	1.041 ? 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:	4.165 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.62 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.26 ? 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
NPO17756	Licania intrapetiolaris	Species	Chrysobalanaceae	Eukaryota	roots	n.a.	n.a.	PMID[11325234]
NPO17756	Licania intrapetiolaris	Species	Chrysobalanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17756	Licania intrapetiolaris	Species	Chrysobalanaceae	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
EC50	1
IZ	1

Activity Type	# Activity
Cell line	1
Organism	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
NPT91	Cell line	KB	Homo sapiens	EC50	=	0.8	ug.mL-1	DOI[10.1039/C2MD20199B]
NPT21	Organism	Aspergillus niger	Aspergillus niger	IZ	=	21.0	mm	DOI[10.1039/C2MD20199B]

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 NPC87630 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	7128
0.1-0.2	38054
0.2-0.3	4509
0.3-0.4	63
0.4-0.5	53
0.5-0.6	35
0.6-0.7	8
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.942	High Similarity	NPC179128
0.8108	Intermediate Similarity	NPC116292
0.7183	Intermediate Similarity	NPC479943
0.7123	Intermediate Similarity	NPC475889
0.7123	Intermediate Similarity	NPC7613
0.7123	Intermediate Similarity	NPC479942
0.6986	Remote Similarity	NPC479940
0.6986	Remote Similarity	NPC7644
0.68	Remote Similarity	NPC479941
0.679	Remote Similarity	NPC486751
0.6667	Remote Similarity	NPC238397
0.6538	Remote Similarity	NPC127933
0.6494	Remote Similarity	NPC471363
0.6024	Remote Similarity	NPC208293
0.5714	Remote Similarity	NPC481025
0.5714	Remote Similarity	NPC602188
0.5625	Remote Similarity	NPC330003
0.5625	Remote Similarity	NPC88013
0.5625	Remote Similarity	NPC470321
0.5625	Remote Similarity	NPC264867
0.5625	Remote Similarity	NPC473207
0.5517	Remote Similarity	NPC162569
0.5517	Remote Similarity	NPC35160
0.55	Remote Similarity	NPC201880
0.55	Remote Similarity	NPC479497
0.55	Remote Similarity	NPC81567
0.55	Remote Similarity	NPC329623
0.55	Remote Similarity	NPC488652
0.55	Remote Similarity	NPC609711
0.5435	Remote Similarity	NPC481026
0.5432	Remote Similarity	NPC217921
0.5432	Remote Similarity	NPC135015
0.5341	Remote Similarity	NPC267469
0.5316	Remote Similarity	NPC488659
0.5316	Remote Similarity	NPC604149
0.5309	Remote Similarity	NPC128795
0.5301	Remote Similarity	NPC488964
0.5301	Remote Similarity	NPC184512
0.5244	Remote Similarity	NPC488658
0.5244	Remote Similarity	NPC488655
0.5244	Remote Similarity	NPC609715
0.5158	Remote Similarity	NPC320734
0.5122	Remote Similarity	NPC134270
0.5122	Remote Similarity	NPC488660
0.5122	Remote Similarity	NPC488657
0.5122	Remote Similarity	NPC488654
0.5122	Remote Similarity	NPC479491
0.5122	Remote Similarity	NPC609880
0.5059	Remote Similarity	NPC125423

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC87630 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4152
0.1-0.2	4917
0.2-0.3	81
0.3-0.4	0
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