NPASS Compound

Natural Product: NPC325805

Natural Product ID	NPC325805
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Esulatin I
IUPAC Name	[(1R,2R,3aR,5R,6E,11R,13R,13aS)-1,3a,11,13-tetraacetyloxy-2,5,8,8-tetramethyl-12-methylidene-4,9-dioxo-3,5,10,11,13,13a-hexahydro-1H-cyclopenta[12]annulen-2-yl] benzoate
Synonyms	Esulatin I
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1812475
PubChem CID	53359848
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0002877] Jatrophane and cyclojatrophane 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 89 91 0 0 0 0 0 0 0 0999 V2000 -3.8857 0.6557 4.4822 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6922 1.3771 3.1935 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8647 2.6204 3.1487 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3272 0.7105 2.0435 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1414 1.3544 0.8322 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2206 1.0595 -0.1925 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5973 -0.3691 -0.2605 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7581 -0.9230 0.8482 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8123 -1.2208 -1.4250 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9274 -2.2472 -1.1018 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1938 -0.5336 -2.6935 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5875 -2.0688 -1.7224 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4114 -1.5071 -1.9220 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1535 -2.2398 -2.2148 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.3303 -2.3769 -1.0545 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0408 -3.5538 -0.7030 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3037 -1.4390 -0.1084 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1906 -0.0045 -0.2539 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5871 0.6978 0.8172 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8259 1.3445 0.2071 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6415 2.0410 -0.9050 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0879 1.8761 1.3126 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1355 2.0571 2.6631 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3910 1.2231 3.4244 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8079 3.2389 3.2692 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6269 0.5655 -0.4170 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8105 1.7834 0.1895 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0679 2.9755 -0.4877 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1307 2.9007 -1.7353 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2539 4.2487 0.2440 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5385 -0.4757 0.0707 C 0 0 2 0 0 0 0 0 0 0 0 0 1.8197 -1.7450 -0.4106 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5605 -0.5964 1.5763 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8014 -0.5867 -0.4929 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8414 0.2841 -0.5070 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6786 1.3701 0.0773 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1285 -0.0014 -1.1722 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3595 -1.1721 -1.8269 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5787 -1.4497 -2.4533 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5940 -0.5176 -2.4174 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3557 0.6661 -1.7538 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1471 0.9312 -1.1378 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2118 -1.8922 1.2144 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9543 -2.2508 1.8272 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0136 -2.2039 1.1985 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9486 -2.7012 3.2640 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5245 -1.8149 -3.5149 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9625 0.7393 5.0563 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0960 -0.4121 4.2116 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7802 1.0867 4.9901 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3631 2.5065 1.0579 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8751 1.3320 -1.2081 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1341 1.6646 0.0173 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7059 -1.7520 -0.5164 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3273 -2.5968 -2.0613 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4869 -3.1205 -0.5785 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1339 0.0321 -2.5750 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3575 0.0830 -3.0903 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3743 -1.3444 -3.4488 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6824 -3.1434 -1.7717 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3678 -0.4341 -1.9007 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5660 -3.2848 -2.4960 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2854 0.3047 -1.2291 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9327 0.1237 1.6566 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4336 2.6256 -1.3807 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6853 2.0859 -1.3808 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8946 3.0805 3.3810 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6345 4.1560 2.6434 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3346 3.4472 4.2526 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7995 0.7225 -1.5322 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6846 4.1327 1.2486 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8410 4.9621 -0.3737 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2237 4.6858 0.3852 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9810 -1.9325 -1.4629 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1541 -2.6009 0.1849 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4023 -0.0777 2.0511 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5993 -0.2685 1.9799 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6648 -1.6801 1.8784 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6074 -1.9443 -1.8928 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7615 -2.3770 -2.9716 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5595 -0.6911 -2.8911 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1807 1.3948 -1.7383 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9669 1.8534 -0.6229 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9175 -3.1243 3.5245 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1562 -3.5021 3.3424 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6498 -1.8165 3.8687 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8836 -0.7549 -3.6819 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8987 -2.3651 -4.4045 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5657 -1.8858 -3.5407 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 7 9 1 0 9 10 1 0 9 11 1 0 9 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 2 0 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 2 0 19 22 1 0 22 23 1 0 23 24 2 0 23 25 1 0 18 26 1 0 26 27 1 0 27 28 1 0 28 29 2 0 28 30 1 0 26 31 1 0 31 32 1 0 31 33 1 0 31 34 1 6 34 35 1 0 35 36 2 0 35 37 1 0 37 38 2 0 38 39 1 0 39 40 2 0 40 41 1 0 41 42 2 0 17 43 1 1 43 44 1 0 44 45 2 0 44 46 1 0 14 47 1 0 20 5 1 0 42 37 1 0 32 17 1 0 1 48 1 0 1 49 1 0 1 50 1 0 5 51 1 1 6 52 1 0 6 53 1 0 10 54 1 0 10 55 1 0 10 56 1 0 11 57 1 0 11 58 1 0 11 59 1 0 12 60 1 0 13 61 1 0 14 62 1 6 18 63 1 6 19 64 1 1 21 65 1 0 21 66 1 0 25 67 1 0 25 68 1 0 25 69 1 0 26 70 1 6 30 71 1 0 30 72 1 0 30 73 1 0 32 74 1 0 32 75 1 0 33 76 1 0 33 77 1 0 33 78 1 0 38 79 1 0 39 80 1 0 40 81 1 0 41 82 1 0 42 83 1 0 46 84 1 0 46 85 1 0 46 86 1 0 47 87 1 0 47 88 1 0 47 89 1 0 M END

Standard InCHIKey	HKKQYNWKQBESIC-KCABZQHESA-N
Standard InCHI	InChI=1S/C35H42O12/c1-19-15-16-33(7,8)27(40)17-26(43-21(3)36)20(2)29(44-22(4)37)28-31(45-23(5)38)34(9,18-35(28,30(19)41)46-24(6)39)47-32(42)25-13-11-10-12-14-25/h10-16,19,26,28-29,31H,2,17-18H2,1,3-9H3/b16-15+/t19-,26-,28+,29+,31-,34-,35-/m1/s1
SMILES	CC(=O)O[C@@H]1CC(=O)C(C)(C)/C=C/[C@H](C(=O)[C@@]2([C@@H]([C@H](C1=C)OC(=O)C)[C@@H](OC(=O)C)[C@](C2)(C)OC(=O)c1ccccc1)OC(=O)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	654.27	Volume:	662.092 ? Van der Waals volume.
Dense:	0.988	LogP:	2.828 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.828 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.753 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	30.0
TPSA:	165.64 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.246	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.52	Fsp³:	0.514
MCE-18:	108.075 ? 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:	0.777	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.015 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.274	Promiscuous compounds:	0.101

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.909	MDCK Permeability:	-4.613
Pgp-inhibitor:	1.0	Pgp-substrate:	0.003
PAMPA:	0.589 ? 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%):	0.666	30% Bioavailability (F30%):	0.98
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.998
Plasma Protein Binding (PPB):	85.533%	Volume Distribution (VD):	-0.156
Fu:	16.542% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.001
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.01
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.011	CYP3A4-substrate:	0.003
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.985 ? 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):

4.91

Half-life (T1/2):

0.449

ADMET: Toxicity

hERG Blockers:	0.004	hERG Blockers (10um):	0.021
Human Hepatotoxicity (H-HT):	0.685	Drug-induced Liver Injury (DILI):	0.998
AMES Toxicity:	0.845	Rat Oral Acute Toxicity:	0.1
Maximum Recommended Daily Dose:	0.371	Skin Sensitization:	1.0
Carcinogencity:	0.696	Eye Corrosion:	0.003
Eye Irritation:	0.364	Respiratory Toxicity:	0.177
Drug-induced Neurotoxicity:	0.686	Ototoxicity:	0.239
Hematotoxicity:	0.423	Drug-induced Nephrotoxicity:	0.979
Genotoxicity:	0.999	RPMI-8226 Immunitoxicity:	0.212
A549 Cytotoxicity:	0.637	Hek293 Cytotoxicity:	0.572
BCF:	0.646 ? 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:	3.553 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.239 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.837 ? 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
NPO13882	Euphorbia grandicornis	Species	Euphorbiaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[21319774]
NPO3099	Euphorbia esula	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21612217]
NPO3099	Euphorbia esula	Species	Euphorbiaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[21612217]
NPO3099	Euphorbia esula	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27447736]
NPO13882	Euphorbia grandicornis	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27731641]
NPO3099	Euphorbia esula	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32233482]
NPO3099	Euphorbia esula	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3099	Euphorbia esula	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3099	Euphorbia esula	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3099	Euphorbia esula	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13882	Euphorbia grandicornis	Species	Euphorbiaceae	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
Ratio	2
GI	6

Activity Type	# Activity
Cell line	6
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT668	Individual protein	P-glycoprotein 1	Homo sapiens	Ratio	=	3.9	n.a.	PMID[21612217]
NPT668	Individual protein	P-glycoprotein 1	Homo sapiens	Ratio	=	19.9	n.a.	PMID[21612217]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT165	Cell line	HeLa	Homo sapiens	GI	=	15.4	%	PMID[21612217]
NPT2738	Cell line	Ishikawa	Homo sapiens	GI	=	8.0	%	PMID[21612217]
NPT83	Cell line	MCF7	Homo sapiens	GI	=	12.7	%	PMID[21612217]
NPT165	Cell line	HeLa	Homo sapiens	GI	=	23.8	%	PMID[21612217]
NPT2738	Cell line	Ishikawa	Homo sapiens	GI	=	29.4	%	PMID[21612217]
NPT83	Cell line	MCF7	Homo sapiens	GI	=	60.1	%	PMID[21612217]

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 NPC325805 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	14204
0.1-0.2	33743
0.2-0.3	1631
0.3-0.4	207
0.4-0.5	47
0.5-0.6	14
0.6-0.7	5
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	Natural Product ID
0.7808	Intermediate Similarity	NPC272523
0.7424	Intermediate Similarity	NPC49393
0.7105	Intermediate Similarity	NPC194769
0.7067	Intermediate Similarity	NPC482308
0.6923	Remote Similarity	NPC475660
0.6623	Remote Similarity	NPC482307
0.6375	Remote Similarity	NPC285221
0.6341	Remote Similarity	NPC482253
0.6	Remote Similarity	NPC319556
0.5976	Remote Similarity	NPC482254
0.5698	Remote Similarity	NPC40919
0.5676	Remote Similarity	NPC78127
0.5542	Remote Similarity	NPC482300
0.5432	Remote Similarity	NPC196683
0.5385	Remote Similarity	NPC470189
0.5357	Remote Similarity	NPC86772
0.5357	Remote Similarity	NPC482315
0.5333	Remote Similarity	NPC470192
0.5176	Remote Similarity	NPC482314
0.5172	Remote Similarity	NPC482310
0.5172	Remote Similarity	NPC482302
0.5165	Remote Similarity	NPC207531
0.5063	Remote Similarity	NPC470188

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC325805 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4275
0.1-0.2	4795
0.2-0.3	80
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