NPASS Compound

Natural Product: NPC476800

Natural Product ID	NPC476800
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[(1R,3S,5S,6aR,7S,8S,10R,10aR)-1,3-diacetyloxy-10-methoxy-7,8-dimethyl-7-(3-methylidenepent-4-enyl)-1,3,5,6,6a,8,9,10-octahydrobenzo[d][2]benzofuran-5-yl] 2-methylbutanoate
IUPAC Name	[(1R,3S,5S,6aR,7S,8S,10R,10aR)-1,3-diacetyloxy-10-methoxy-7,8-dimethyl-7-(3-methylidenepent-4-enyl)-1,3,5,6,6a,8,9,10-octahydrobenzo[d][2]benzofuran-5-yl] 2-methylbutanoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL456511
PubChem CID	44593673
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 82 84 0 0 0 0 0 0 0 0999 V2000 -3.4348 5.6385 -0.9657 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3375 5.5706 -1.6865 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5533 4.3445 -1.6948 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4654 4.2937 -2.4158 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0563 3.1955 -0.8534 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0998 2.0572 -0.9875 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4675 0.8307 -0.1662 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4891 1.2672 1.2522 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8853 0.4560 -0.5130 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1251 0.0050 -1.9001 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2737 -0.5715 0.5194 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4193 -1.8235 0.4509 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0417 -1.6469 -0.0409 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6185 -0.3392 -0.5403 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8565 -0.0219 -0.4531 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3981 -0.1162 0.9703 C 0 0 2 0 0 0 0 0 0 0 0 0 2.7849 0.1284 0.9487 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4041 1.1386 1.6448 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 1.8734 2.3366 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8563 1.2997 1.5480 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3781 2.4519 2.3754 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7944 3.7681 1.9718 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2933 1.5368 0.1176 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0934 -1.5453 1.3019 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0531 -2.1778 0.8594 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3551 -3.5958 0.9896 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7170 -3.9419 -0.2800 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8811 -2.8131 -1.0604 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1257 -2.5717 -1.9699 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0923 -2.5756 -3.3151 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2289 -2.8005 -3.7914 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0357 -2.3078 -4.2603 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7033 -4.3969 1.4960 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5387 -5.1343 2.6569 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5761 -5.0656 3.2387 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6076 -5.9876 3.2318 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2084 -2.6601 -0.3587 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8838 -3.6375 0.2918 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7549 4.7874 -0.3803 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0585 6.5186 -0.9183 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0638 6.4488 -2.2526 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1659 5.1501 -2.9887 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1252 3.4035 -2.4381 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0829 2.9563 -1.2172 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1303 3.6075 0.1648 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1113 2.4641 -0.6830 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0237 1.7939 -2.0601 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8083 2.1115 1.4941 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3738 0.5271 2.0286 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5042 1.7535 1.4316 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5574 1.3406 -0.2749 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4598 0.4858 -2.6579 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1932 -1.0902 -2.0556 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1562 0.3678 -2.2011 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2429 -0.1012 1.5208 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3524 -0.7705 0.3453 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5115 -2.2474 1.4680 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7497 -0.4131 -1.6816 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4026 -0.8356 -1.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1016 0.8974 -0.9712 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9699 0.6223 1.6142 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3410 0.3751 1.9482 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4768 2.5000 2.2320 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2054 2.3033 3.4599 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8315 3.9171 0.8682 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4608 4.5707 2.3908 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7779 3.9516 2.3374 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5381 2.2121 -0.3570 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2925 1.9727 0.1064 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3023 0.5477 -0.3854 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7958 -2.0455 1.9445 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1866 -3.7210 1.6763 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8092 -2.9907 -1.6294 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1847 -1.2453 -4.4571 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8502 -2.9294 -5.1558 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9406 -2.7695 -3.7664 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1447 -6.9199 3.5794 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0969 -5.4619 4.0840 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3679 -6.2698 2.4690 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5887 -3.2636 1.0735 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4792 -4.2896 -0.4290 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2043 -4.3474 0.7754 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 6 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 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 1 0 21 22 1 0 20 23 1 0 16 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 2 0 30 32 1 0 26 33 1 0 33 34 1 0 34 35 2 0 34 36 1 0 12 37 1 0 37 38 1 0 14 7 1 0 28 13 1 0 13 25 1 1 1 39 1 0 1 40 1 0 2 41 1 0 4 42 1 0 4 43 1 0 5 44 1 0 5 45 1 0 6 46 1 0 6 47 1 0 8 48 1 0 8 49 1 0 8 50 1 0 9 51 1 1 10 52 1 0 10 53 1 0 10 54 1 0 11 55 1 0 11 56 1 0 12 57 1 1 14 58 1 6 15 59 1 0 15 60 1 0 16 61 1 1 20 62 1 0 21 63 1 0 21 64 1 0 22 65 1 0 22 66 1 0 22 67 1 0 23 68 1 0 23 69 1 0 23 70 1 0 24 71 1 0 26 72 1 1 28 73 1 6 32 74 1 0 32 75 1 0 32 76 1 0 36 77 1 0 36 78 1 0 36 79 1 0 38 80 1 0 38 81 1 0 38 82 1 0 M END

Standard InCHIKey	PRXYABXGJNKXKE-JQOSQATJSA-N
Standard InCHI	InChI=1S/C30H44O8/c1-10-17(3)12-13-29(8)19(5)14-25(34-9)30-23(27(35-20(6)31)38-28(30)36-21(7)32)15-22(16-24(29)30)37-26(33)18(4)11-2/h10,15,18-19,22,24-25,27-28H,1,3,11-14,16H2,2,4-9H3/t18?,19-,22+,24+,25+,27+,28-,29-,30-/m0/s1
SMILES	C=CC(=C)CC[C@@]1(C)[C@@H](C)C[C@H]([C@]23[C@@H]1C[C@H](OC(=O)C(CC)C)C=C3[C@@H](O[C@@H]2OC(=O)C)OC(=O)C)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	532.3	Volume:	556.27 ? Van der Waals volume.
Dense:	0.957	LogP:	4.209 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.595 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.935 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	13.0	Rigid Bonds:	20.0
TPSA:	97.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.162	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.839	Fsp³:	0.7
MCE-18:	91.588 ? 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:	0.65	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.024 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.002 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.365	Promiscuous compounds:	0.563

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.993	MDCK Permeability:	-4.674
Pgp-inhibitor:	0.931	Pgp-substrate:	0.072
PAMPA:	0.029 ? 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%):	0.986	30% Bioavailability (F30%):	0.988
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.998	MRP1:	0.998
Plasma Protein Binding (PPB):	87.938%	Volume Distribution (VD):	0.07
Fu:	10.736% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.923
OATP1B3 inhibitor:	0.716	BCRP inhibitor:	0.416
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.205
CYP2C19-inhibitor:	0.026	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.241	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.051
CYP3A4-inhibitor:	0.384	CYP3A4-substrate:	0.882
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.999 ? 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):

9.592

Half-life (T1/2):

0.727

ADMET: Toxicity

hERG Blockers:	0.096	hERG Blockers (10um):	0.354
Human Hepatotoxicity (H-HT):	0.685	Drug-induced Liver Injury (DILI):	0.977
AMES Toxicity:	0.983	Rat Oral Acute Toxicity:	0.876
Maximum Recommended Daily Dose:	0.982	Skin Sensitization:	0.999
Carcinogencity:	0.767	Eye Corrosion:	0.0
Eye Irritation:	0.008	Respiratory Toxicity:	0.563
Drug-induced Neurotoxicity:	0.973	Ototoxicity:	0.494
Hematotoxicity:	0.842	Drug-induced Nephrotoxicity:	0.972
Genotoxicity:	0.992	RPMI-8226 Immunitoxicity:	0.335
A549 Cytotoxicity:	0.938	Hek293 Cytotoxicity:	0.655
BCF:	0.926 ? 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:	3.861 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.563 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.111 ? 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
NPO24670	Casearia lucida	Species	Salicaceae	Eukaryota	Barks	n.a.	n.a.	PMID[11858738]
NPO31460	Casearia grewiifolia	Species	Salicaceae	Eukaryota	n.a.	bark	n.a.	PMID[15730240]
NPO31460	Casearia grewiifolia	Species	Salicaceae	Eukaryota	bark	in the campus of Khon Kaen University, Khon Kaen, Thailand	2001-SEP	PMID[15730240]
NPO31460	Casearia grewiifolia	Species	Salicaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[17567069]
NPO31460	Casearia grewiifolia	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26516994]
NPO24670	Casearia lucida	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31460	Casearia grewiifolia	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24670	Casearia lucida	Species	Salicaceae	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	14
MIC	1

Activity Type	# Activity
Cell line	10
Non-molecular	3
Organism	2

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
NPT179	Cell line	A2780	Homo sapiens	IC50	=	2.9	ug.mL-1	PMID[11858738]
NPT134	Cell line	SK-BR-3	Homo sapiens	IC50	=	3.5	ug.mL-1	PMID[11858738]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	3.0	ug.mL-1	PMID[11858738]
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	1.0	ug.mL-1	PMID[11858738]
NPT4486	Cell line	LX-1	Homo sapiens	IC50	=	1.2	ug.mL-1	PMID[11858738]
NPT111	Cell line	K562	Homo sapiens	IC50	=	1.4	ug.mL-1	PMID[11858738]
NPT5611	Cell line	ABAE	Homo sapiens	IC50	=	0.8	ug.mL-1	PMID[11858738]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	1.3	ug.mL-1	PMID[11858738]
NPT91	Cell line	KB	Homo sapiens	IC50	=	7.6	ug.mL-1	PMID[15730240]
NPT639	Cell line	NCI-H187	Homo sapiens	IC50	=	0.8	ug.mL-1	PMID[15730240]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	1.4	ug.mL-1	PMID[11858738]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	2.9	ug.mL-1	PMID[11858738]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	MIC	=	12.5	ug.mL-1	PMID[15730240]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	4.0	ug.mL-1	PMID[15730240]
NPT485	Organism	Plasmodium falciparum (isolate K1 / Thailand)	Plasmodium falciparum K1	IC50	=	3.2	ug.mL-1	PMID[15730240]

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 NPC476800 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	22261
0.1-0.2	25715
0.2-0.3	1741
0.3-0.4	28
0.4-0.5	43
0.5-0.6	29
0.6-0.7	18
0.7-0.8	0
0.8-0.85	7
0.85-0.9	4
0.9-0.95	3
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC471366
1.0	High Similarity	NPC488237
0.9474	High Similarity	NPC472188
0.9138	High Similarity	NPC488236
0.9016	High Similarity	NPC472187
0.8947	High Similarity	NPC171598
0.8689	High Similarity	NPC473545
0.8644	High Similarity	NPC318917
0.8644	High Similarity	NPC481019
0.8448	Intermediate Similarity	NPC472189
0.8305	Intermediate Similarity	NPC481018
0.8197	Intermediate Similarity	NPC472186
0.8167	Intermediate Similarity	NPC481020
0.8065	Intermediate Similarity	NPC488649
0.8033	Intermediate Similarity	NPC471362
0.8033	Intermediate Similarity	NPC471372
0.7937	Intermediate Similarity	NPC481017
0.7778	Intermediate Similarity	NPC473204
0.7188	Intermediate Similarity	NPC488235
0.6883	Remote Similarity	NPC488962
0.6875	Remote Similarity	NPC606965
0.6818	Remote Similarity	NPC479937
0.6769	Remote Similarity	NPC132395
0.6769	Remote Similarity	NPC471364
0.6769	Remote Similarity	NPC600724
0.6667	Remote Similarity	NPC488963
0.6522	Remote Similarity	NPC475889
0.6522	Remote Similarity	NPC7613
0.6522	Remote Similarity	NPC479942
0.6308	Remote Similarity	NPC603601
0.6286	Remote Similarity	NPC238397
0.6269	Remote Similarity	NPC488651
0.6269	Remote Similarity	NPC488648
0.6197	Remote Similarity	NPC48548
0.6176	Remote Similarity	NPC479939
0.6143	Remote Similarity	NPC471365
0.6029	Remote Similarity	NPC479934
0.5974	Remote Similarity	NPC473216
0.5946	Remote Similarity	NPC127933
0.5942	Remote Similarity	NPC479935
0.5942	Remote Similarity	NPC479936
0.589	Remote Similarity	NPC471363
0.5857	Remote Similarity	NPC479943
0.5694	Remote Similarity	NPC479940
0.5694	Remote Similarity	NPC7644
0.5676	Remote Similarity	NPC488219
0.5616	Remote Similarity	NPC88013
0.56	Remote Similarity	NPC125423
0.56	Remote Similarity	NPC488221
0.56	Remote Similarity	NPC488220
0.56	Remote Similarity	NPC488216
0.557	Remote Similarity	NPC473399
0.5556	Remote Similarity	NPC479938
0.5526	Remote Similarity	NPC40728
0.5441	Remote Similarity	NPC488650
0.5441	Remote Similarity	NPC481022
0.5405	Remote Similarity	NPC217921
0.5405	Remote Similarity	NPC135015
0.5333	Remote Similarity	NPC479941
0.5316	Remote Similarity	NPC486752
0.527	Remote Similarity	NPC128795
0.5244	Remote Similarity	NPC486759
0.5122	Remote Similarity	NPC162569
0.5122	Remote Similarity	NPC35160
0.506	Remote Similarity	NPC488217
0.506	Remote Similarity	NPC488218

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476800 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7249
0.1-0.2	1884
0.2-0.3	17
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