NPASS Compound

Natural Product: NPC478275

Natural Product ID	NPC478275
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	IFLHDGGEJKVLAF-ASZZAFOJSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	125115324
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides [CHEMONTID:0003678] Flavonoid 3-O-p-coumaroyl glycosides

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 96101 0 0 0 0 0 0 0 0999 V2000 4.2696 2.4415 2.3306 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8851 1.9106 2.2895 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0437 2.0892 3.2100 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4950 1.1822 1.1859 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2310 0.6223 1.0042 C 0 0 2 0 0 0 0 0 0 0 0 0 1.2441 -0.8775 0.8000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.1825 -1.4862 1.8067 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4876 -1.0132 1.5977 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2308 -1.1910 0.4545 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7515 -1.8212 -0.5049 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5931 -0.6440 0.3443 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2858 -0.8131 -0.7478 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6326 -0.3263 -0.9831 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2519 -0.5725 -2.1956 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5249 -0.1210 -2.4516 C 0 0 0 0 0 0 0 0 0 0 0 0 10.2143 0.5959 -1.4871 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6037 0.8421 -0.2829 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3325 0.3813 -0.0504 C 0 0 0 0 0 0 0 0 0 0 0 0 11.5159 1.0650 -1.7323 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0296 -1.3396 1.0365 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9822 -0.8362 0.1262 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9089 0.5813 -0.1246 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5192 1.1392 -0.2285 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5140 2.5329 -0.1693 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9788 3.3681 -1.1587 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4502 2.8678 -2.2098 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9450 4.8488 -1.0333 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6200 1.0169 -1.2583 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6248 2.0276 -1.1786 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7747 2.4416 -0.0091 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3101 2.4379 -2.3636 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1839 3.3553 -2.5007 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6617 4.2157 -1.4445 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0264 4.5940 -1.4740 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5525 5.4956 -0.6028 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7866 6.1040 0.3726 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4598 5.7507 0.4149 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9219 4.8313 -0.4758 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3445 7.0165 1.2489 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2201 -1.1757 0.7913 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5735 -2.4946 0.9797 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1105 -3.0956 2.1711 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4376 -2.4035 2.9527 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3904 -4.4024 2.4664 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9338 -4.9872 3.6370 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2285 -6.3054 3.9125 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9923 -6.9964 2.9692 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4437 -6.4118 1.8083 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1473 -5.0833 1.5299 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5608 -4.5163 0.4495 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3060 -3.2264 0.1230 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8428 -2.7361 -1.1267 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9285 -1.4432 -1.5267 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4250 -1.0705 -2.7768 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8617 -2.0370 -3.6793 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7839 -3.3490 -3.2924 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2914 -3.6879 -2.0580 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3584 -1.6648 -4.9293 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2838 -8.3334 3.2621 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1754 -4.2723 4.5556 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9756 1.7385 2.8181 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6149 2.7608 1.3177 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2523 3.3442 3.0074 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6045 0.8690 1.8993 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6168 -1.0829 -0.2048 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9031 -1.2218 2.8568 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1372 -2.6029 1.7887 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0395 -0.0947 1.1683 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7937 -1.3736 -1.5530 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7162 -1.1333 -2.9522 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0180 -0.3110 -3.4058 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1304 1.4074 0.4957 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9030 0.6130 0.9340 H 0 0 0 0 0 0 0 0 0 0 0 0 12.3319 0.5773 -1.4345 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9171 -1.4897 -0.7524 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3218 1.1611 0.7602 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9404 0.7291 -1.1563 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8019 5.2006 -0.3931 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0377 5.2110 -0.5486 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0846 5.3289 -2.0219 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0376 1.8713 -3.2938 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6369 3.5289 -3.5239 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6517 4.1202 -2.2441 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6180 5.7501 -0.6748 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8531 6.2256 1.1798 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8494 4.6931 -0.4019 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2031 7.0083 2.2478 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8806 -6.7773 4.8220 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0311 -7.0006 1.1191 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6366 -0.6651 -0.8606 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4921 -0.0422 -3.0895 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1133 -4.1275 -3.9643 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2377 -4.7377 -1.7725 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3305 -2.2645 -5.7303 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1203 -8.4931 3.8287 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6704 -3.7413 5.2864 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 1 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 16 19 1 0 6 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 2 0 25 27 1 0 22 28 1 0 28 29 1 0 29 30 2 0 29 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 36 37 1 0 37 38 2 0 36 39 1 0 21 40 1 0 40 41 1 0 41 42 1 0 42 43 2 0 42 44 1 0 44 45 2 0 45 46 1 0 46 47 2 0 47 48 1 0 48 49 2 0 49 50 1 0 50 51 1 0 51 52 1 0 52 53 2 0 53 54 1 0 54 55 2 0 55 56 1 0 56 57 2 0 55 58 1 0 47 59 1 0 45 60 1 0 23 5 1 0 38 33 1 0 51 41 2 0 57 52 1 0 18 13 1 0 49 44 1 0 1 61 1 0 1 62 1 0 1 63 1 0 5 64 1 1 6 65 1 6 7 66 1 0 7 67 1 0 11 68 1 0 12 69 1 0 14 70 1 0 15 71 1 0 17 72 1 0 18 73 1 0 19 74 1 0 21 75 1 6 22 76 1 1 23 77 1 6 27 78 1 0 27 79 1 0 27 80 1 0 31 81 1 0 32 82 1 0 34 83 1 0 35 84 1 0 37 85 1 0 38 86 1 0 39 87 1 0 46 88 1 0 48 89 1 0 53 90 1 0 54 91 1 0 56 92 1 0 57 93 1 0 58 94 1 0 59 95 1 0 60 96 1 0 M END

Standard InCHIKey	IFLHDGGEJKVLAF-ASZZAFOJSA-N
Standard InCHI	InChI=1S/C43H36O17/c1-22(44)55-39-33(21-54-34(51)17-7-24-3-11-27(46)12-4-24)58-43(42(41(39)56-23(2)45)59-35(52)18-8-25-5-13-28(47)14-6-25)60-40-37(53)36-31(50)19-30(49)20-32(36)57-38(40)26-9-15-29(48)16-10-26/h3-20,33,39,41-43,46-50H,21H2,1-2H3/b17-7+,18-8-/t33-,39-,41+,42-,43+/m1/s1
SMILES	CC(=O)O[C@@H]1[C@@H](COC(=O)/C=C/c2ccc(cc2)O)O[C@H]([C@@H]([C@H]1OC(=O)C)OC(=O)/C=Cc1ccc(cc1)O)Oc1c(=O)c2c(cc(cc2oc1c1ccc(cc1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	824.2	Volume:	797.65 ? Van der Waals volume.
Dense:	1.033	LogP:	2.647 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.388 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.549 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	16.0	Rigid Bonds:	42.0
TPSA:	255.02 ? Topological Polar Surface Area.	H-Bond Acceptor:	17.0
H-Bond Donor:	5.0	Rings:	6.0
Heavy Atoms:	17.0

MedChem Properties

QED Drug-Likeness Score:	0.064	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.702	Fsp³:	0.186
MCE-18:	127.843 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	1.0	Fluc inhibitor:	1.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.879 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.643 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.406	Promiscuous compounds:	0.816

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.023	MDCK Permeability:	-5.086
Pgp-inhibitor:	0.906	Pgp-substrate:	0.019
PAMPA:	0.876 ? 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%):	0.988	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.013
Plasma Protein Binding (PPB):	92.626%	Volume Distribution (VD):	-0.044
Fu:	8.573% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.074
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.034
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.709
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.379
CYP2D6-inhibitor:	0.014	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.869
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.991 ? 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):

2.77

Half-life (T1/2):

2.259

ADMET: Toxicity

hERG Blockers:	0.155	hERG Blockers (10um):	0.517
Human Hepatotoxicity (H-HT):	0.668	Drug-induced Liver Injury (DILI):	0.901
AMES Toxicity:	0.818	Rat Oral Acute Toxicity:	0.031
Maximum Recommended Daily Dose:	0.803	Skin Sensitization:	1.0
Carcinogencity:	0.052	Eye Corrosion:	0.0
Eye Irritation:	0.393	Respiratory Toxicity:	0.009
Drug-induced Neurotoxicity:	0.047	Ototoxicity:	0.17
Hematotoxicity:	0.003	Drug-induced Nephrotoxicity:	0.172
Genotoxicity:	0.999	RPMI-8226 Immunitoxicity:	0.077
A549 Cytotoxicity:	0.973	Hek293 Cytotoxicity:	0.997
BCF:	0.716 ? 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:	4.092 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.899 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.781 ? 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
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	roots	n.a.	n.a.	PMID[10346940]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26722868]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO19205	Buxus sempervirens	Species	Buxaceae	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	3
Ratio IC50	3

Activity Type	# Activity
Cell line	1
Organism	2
Others	3

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
NPT165	Cell line	HeLa	Homo sapiens	IC50	<	3000.0	nM	PMID[26722868]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	900.0	nM	PMID[26722868]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	5000.0	nM	PMID[26722868]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	5.6	n.a.	PMID[26722868]
NPT27	Others	Unspecified	n.a.	Ratio IC50	<	3.3	n.a.	PMID[26722868]
NPT27	Others	Unspecified	n.a.	Ratio IC50	<	0.6	n.a.	PMID[26722868]

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 NPC478275 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	15505
0.1-0.2	30555
0.2-0.3	3105
0.3-0.4	425
0.4-0.5	193
0.5-0.6	43
0.6-0.7	24
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC478277
1.0	High Similarity	NPC478276
1.0	High Similarity	NPC92815
0.7292	Intermediate Similarity	NPC101399
0.7292	Intermediate Similarity	NPC217822
0.7292	Intermediate Similarity	NPC11847
0.7292	Intermediate Similarity	NPC198938
0.7245	Intermediate Similarity	NPC218161
0.6932	Remote Similarity	NPC104677
0.6832	Remote Similarity	NPC96605
0.6832	Remote Similarity	NPC280642
0.6771	Remote Similarity	NPC473862
0.6768	Remote Similarity	NPC221288
0.6768	Remote Similarity	NPC194836
0.6768	Remote Similarity	NPC91493
0.6768	Remote Similarity	NPC605081
0.67	Remote Similarity	NPC85751
0.67	Remote Similarity	NPC19240
0.65	Remote Similarity	NPC104883
0.65	Remote Similarity	NPC488679
0.6436	Remote Similarity	NPC205824
0.633	Remote Similarity	NPC474093
0.633	Remote Similarity	NPC104910
0.625	Remote Similarity	NPC483767
0.625	Remote Similarity	NPC223426
0.625	Remote Similarity	NPC483769
0.625	Remote Similarity	NPC483768
0.625	Remote Similarity	NPC483766
0.619	Remote Similarity	NPC214621
0.619	Remote Similarity	NPC34267
0.6068	Remote Similarity	NPC231787
0.6038	Remote Similarity	NPC483765
0.5963	Remote Similarity	NPC217520
0.5938	Remote Similarity	NPC48093
0.5932	Remote Similarity	NPC275977
0.5929	Remote Similarity	NPC162394
0.5872	Remote Similarity	NPC477895
0.5818	Remote Similarity	NPC470712
0.5789	Remote Similarity	NPC156785
0.5789	Remote Similarity	NPC474522
0.5741	Remote Similarity	NPC81042
0.5702	Remote Similarity	NPC30011
0.5702	Remote Similarity	NPC72554
0.5678	Remote Similarity	NPC25946
0.567	Remote Similarity	NPC216496
0.5575	Remote Similarity	NPC470718
0.5556	Remote Similarity	NPC260504
0.5556	Remote Similarity	NPC85707
0.5556	Remote Similarity	NPC259957
0.5556	Remote Similarity	NPC36138
0.5556	Remote Similarity	NPC241781
0.5556	Remote Similarity	NPC89809
0.5556	Remote Similarity	NPC224530
0.5524	Remote Similarity	NPC470125
0.552	Remote Similarity	NPC97817
0.5439	Remote Similarity	NPC139571
0.5433	Remote Similarity	NPC475179
0.541	Remote Similarity	NPC473554
0.5403	Remote Similarity	NPC487502
0.5385	Remote Similarity	NPC33083
0.536	Remote Similarity	NPC249560
0.53	Remote Similarity	NPC159579
0.53	Remote Similarity	NPC129217
0.5246	Remote Similarity	NPC21359
0.5246	Remote Similarity	NPC460984
0.5196	Remote Similarity	NPC321478
0.5185	Remote Similarity	NPC297503
0.5182	Remote Similarity	NPC477629
0.5169	Remote Similarity	NPC470713
0.514	Remote Similarity	NPC129264
0.513	Remote Similarity	NPC164704
0.5098	Remote Similarity	NPC117478
0.5088	Remote Similarity	NPC470416
0.5046	Remote Similarity	NPC477628
0.5045	Remote Similarity	NPC188815

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC478275 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4197
0.1-0.2	4897
0.2-0.3	51
0.3-0.4	4
0.4-0.5	1
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