NPASS Compound

Natural Product: NPC325594

Natural Product ID	NPC325594
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Ethyl Lansiolate
IUPAC Name	ethyl 3-[(1S,2S,6S)-2-[2-[(1S,4aR,6S,8aR)-6-hydroxy-5,5,8a-trimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]ethyl]-1,3-dimethyl-6-prop-1-en-2-ylcyclohex-3-en-1-yl]propanoate
Synonyms	Ethyl Lansiolate
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1782136
PubChem CID	53262848
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001549] Monoterpenoids [CHEMONTID:0001564] Bicyclic monoterpenoids

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 87 89 0 0 0 0 0 0 0 0999 V2000 5.4256 4.7837 -0.0545 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9179 3.8094 0.9678 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5623 2.5545 0.4314 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4159 1.7010 -0.2301 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6125 2.0633 -0.3677 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9350 0.3702 -0.7717 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4851 0.2701 -0.5026 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7800 -0.9907 -0.9751 C 0 0 2 0 0 0 0 0 0 0 0 0 2.8745 -1.1034 -2.4403 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3153 -0.8390 -0.5075 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5579 0.2604 -1.1238 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7342 0.6982 -0.5820 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9291 -0.0174 -0.2480 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8870 -1.0544 0.8168 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0957 -2.3188 0.6025 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6973 -0.5837 2.2518 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9779 0.1956 2.6182 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8076 0.2182 1.3325 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0412 0.9509 0.2853 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4075 2.2042 0.7909 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9008 1.2868 -0.8857 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9575 2.2311 -0.4458 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6871 1.8479 0.7863 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.2136 0.6794 1.5446 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3752 1.0033 3.0388 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2065 -0.4861 1.3414 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8658 2.9770 1.6310 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7539 -2.1682 -1.0156 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2846 -3.2571 -0.4680 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3610 -2.9765 0.5384 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4147 -2.2060 -0.3106 C 0 0 1 0 0 0 0 0 0 0 0 0 4.0750 -3.1572 -1.2285 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7146 -4.4435 -1.2957 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2141 -2.8229 -2.1492 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1836 -2.3336 -2.1142 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6413 5.0835 -0.7688 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3536 4.4227 -0.4889 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6835 5.7213 0.5203 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7615 3.5934 1.6880 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0766 4.2020 1.5593 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2430 0.3782 -1.8307 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4476 -0.4176 -0.1568 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0204 1.1701 -0.9567 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3319 0.3639 0.5937 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7206 -2.1446 -2.7945 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9018 -0.7823 -2.7941 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1877 -0.4443 -3.0116 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2791 -0.8237 0.5610 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4330 0.1153 -2.2497 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2246 1.1925 -1.1226 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0268 1.6629 -1.2117 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4305 1.2818 0.3875 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4533 -0.5039 -1.1244 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0474 -3.0412 1.4397 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3540 -2.7856 -0.3343 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7878 0.0150 2.3756 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6575 -1.4495 2.9171 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5802 -0.3566 3.3569 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7196 1.1661 3.0123 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8844 -0.8479 1.0368 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1774 2.8988 1.2422 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6618 2.0939 1.5869 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9832 2.8026 -0.0308 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2536 1.8347 -1.6318 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2703 0.3924 -1.4239 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6297 2.4137 -1.3355 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4877 3.2403 -0.2742 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7556 1.6486 0.4538 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5380 0.1015 3.6466 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6357 1.7132 3.4050 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3635 1.5531 3.0872 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3120 -0.6571 0.2492 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6818 -1.3748 1.7425 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1764 -0.2817 1.8055 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8405 3.7587 1.0010 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9281 -4.2433 -0.7311 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0490 -2.3533 1.3641 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8640 -3.9068 0.8430 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1748 -1.9047 0.4557 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2766 -5.0760 -2.0271 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9962 -4.9722 -0.7498 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8943 -2.9021 -3.2112 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9307 -3.7136 -2.0244 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7800 -1.9601 -1.8766 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8646 -3.2134 -1.9932 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4286 -2.5413 -3.0688 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7877 -1.4693 -2.3689 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 4 6 1 0 6 7 1 0 8 7 1 1 8 9 1 0 8 10 1 0 10 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 17 18 1 0 18 19 1 0 19 20 1 1 19 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 24 26 1 0 23 27 1 0 10 28 1 0 28 29 2 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 2 0 32 34 1 0 28 35 1 0 31 8 1 0 19 13 1 0 24 18 1 0 1 36 1 0 1 37 1 0 1 38 1 0 2 39 1 0 2 40 1 0 6 41 1 0 6 42 1 0 7 43 1 0 7 44 1 0 9 45 1 0 9 46 1 0 9 47 1 0 10 48 1 1 11 49 1 0 11 50 1 0 12 51 1 0 12 52 1 0 13 53 1 6 15 54 1 0 15 55 1 0 16 56 1 0 16 57 1 0 17 58 1 0 17 59 1 0 18 60 1 6 20 61 1 0 20 62 1 0 20 63 1 0 21 64 1 0 21 65 1 0 22 66 1 0 22 67 1 0 23 68 1 6 25 69 1 0 25 70 1 0 25 71 1 0 26 72 1 0 26 73 1 0 26 74 1 0 27 75 1 0 29 76 1 0 30 77 1 0 30 78 1 0 31 79 1 1 33 80 1 0 33 81 1 0 34 82 1 0 34 83 1 0 34 84 1 0 35 85 1 0 35 86 1 0 35 87 1 0 M END

Standard InCHIKey	MBFTWDFKACXAAV-XXYMEPQGSA-N
Standard InCHI	InChI=1S/C32H52O3/c1-10-35-29(34)18-20-31(8)24(21(2)3)13-11-22(4)25(31)14-15-26-23(5)12-16-27-30(6,7)28(33)17-19-32(26,27)9/h11,24-28,33H,2,5,10,12-20H2,1,3-4,6-9H3/t24-,25-,26-,27-,28-,31-,32+/m0/s1
SMILES	CCOC(=O)CC[C@]1(C)[C@@H](CC[C@H]2C(=C)CC[C@@H]3[C@]2(C)CC[C@@H](C3(C)C)O)C(=CC[C@H]1C(=C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	484.39	Volume:	552.183 ? Van der Waals volume.
Dense:	0.877	LogP:	6.122 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.544 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.797 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	20.0
TPSA:	46.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.28	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.885	Fsp³:	0.781
MCE-18:	66.316 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.798	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.711	Promiscuous compounds:	0.341

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.978	MDCK Permeability:	-4.729
Pgp-inhibitor:	0.931	Pgp-substrate:	0.0
PAMPA:	0.012 ? 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%):	0.005	30% Bioavailability (F30%):	0.026
50% Bioavailability (F50%):	0.934

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.098	MRP1:	0.932
Plasma Protein Binding (PPB):	90.018%	Volume Distribution (VD):	-0.023
Fu:	8.66% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.878
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.502
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.533
CYP2C9-inhibitor:	0.006	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.061	CYP2D6-substrate:	0.005
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.982
CYP2B6-substrate:	0.041	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

11.213

Half-life (T1/2):

0.503

ADMET: Toxicity

hERG Blockers:	0.047	hERG Blockers (10um):	0.379
Human Hepatotoxicity (H-HT):	0.468	Drug-induced Liver Injury (DILI):	0.064
AMES Toxicity:	0.041	Rat Oral Acute Toxicity:	0.142
Maximum Recommended Daily Dose:	0.791	Skin Sensitization:	0.697
Carcinogencity:	0.636	Eye Corrosion:	0.033
Eye Irritation:	0.824	Respiratory Toxicity:	0.726
Drug-induced Neurotoxicity:	0.225	Ototoxicity:	0.68
Hematotoxicity:	0.102	Drug-induced Nephrotoxicity:	0.176
Genotoxicity:	0.018	RPMI-8226 Immunitoxicity:	0.058
A549 Cytotoxicity:	0.068	Hek293 Cytotoxicity:	0.207
BCF:	2.166 ? 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:	4.98 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.202 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.73 ? 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
NPO20633	Lansium domesticum	Species	Meliaceae	Eukaryota	n.a.	exocarp	n.a.	DOI[10.1021/jo00172a004]
NPO20633	Lansium domesticum	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12444710]
NPO20633	Lansium domesticum	Species	Meliaceae	Eukaryota	seeds	n.a.	n.a.	PMID[19299148]
NPO20633	Lansium domesticum	Species	Meliaceae	Eukaryota	twigs	Xishuangbanna, Mengla County, Yunnan Province, China	2005-AUG	PMID[21401117]
NPO20633	Lansium domesticum	Species	Meliaceae	Eukaryota	n.a.	twig	n.a.	PMID[21401117]
NPO20633	Lansium domesticum	Species	Meliaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[30335380]
NPO20633	Lansium domesticum	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20633	Lansium domesticum	Species	Meliaceae	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
MIC	11
Inhibition	1

Activity Type	# Activity
Organism	12

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
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MIC	=	6.25	ug.mL-1	PMID[21401117]
NPT2909	Organism	Shigella flexneri	Shigella flexneri	MIC	>	50.0	ug.mL-1	PMID[21401117]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	7.9	%	PMID[30335380]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	3.12	ug.mL-1	PMID[21401117]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	6.25	ug.mL-1	PMID[21401117]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	3.12	ug.mL-1	PMID[21401117]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	50.0	ug.mL-1	PMID[21401117]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	MIC	>	50.0	ug.mL-1	PMID[21401117]
NPT1277	Organism	Staphylococcus epidermidis ATCC 12228	Staphylococcus epidermidis ATCC 12228	MIC	=	12.5	ug.mL-1	PMID[21401117]
NPT314	Organism	Bacillus cereus	Bacillus cereus	MIC	=	3.12	ug.mL-1	PMID[21401117]
NPT1248	Organism	Serratia marcescens	Serratia marcescens	MIC	>	50.0	ug.mL-1	PMID[21401117]
NPT2227	Organism	Alcaligenes faecalis	Alcaligenes faecalis	MIC	>	50.0	ug.mL-1	PMID[21401117]

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 NPC325594 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	17065
0.1-0.2	25124
0.2-0.3	7078
0.3-0.4	526
0.4-0.5	49
0.5-0.6	8
0.6-0.7	4
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8571	High Similarity	NPC234974
0.7097	Intermediate Similarity	NPC73038
0.6562	Remote Similarity	NPC10349
0.6129	Remote Similarity	NPC478375
0.6061	Remote Similarity	NPC327674
0.6034	Remote Similarity	NPC470428
0.5902	Remote Similarity	NPC608380
0.5857	Remote Similarity	NPC327002
0.5397	Remote Similarity	NPC482141
0.5397	Remote Similarity	NPC482142
0.5224	Remote Similarity	NPC159763
0.5224	Remote Similarity	NPC278386
0.5224	Remote Similarity	NPC124512
0.5147	Remote Similarity	NPC72845

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC325594 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6454
0.1-0.2	2527
0.2-0.3	165
0.3-0.4	3
0.4-0.5	0
0.5-0.6	1
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
0.5224	Remote Similarity	NPD4225	Phase 3

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