NPASS Compound

Natural Product: NPC75747

Natural Product ID	NPC75747
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Alpinoside
IUPAC Name	[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] (2R,4aS,6aR,6aS,6bR,8aR,10S,11R,12aR,14bS)-10,11-dihydroxy-2,6a,6b,9,9,12a-hexamethyl-1-methylidene-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylate
Synonyms	Alpinoside
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1077633
PubChem CID	46882792
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0002049] Terpene glycosides [CHEMONTID:0001580] Triterpene glycosides [CHEMONTID:0002358] Triterpene saponins

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 101106 0 0 0 0 0 0 0 0999 V2000 8.4579 -1.7595 0.6614 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8422 -0.4538 0.3598 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8752 0.1869 -0.6173 C 0 0 1 0 0 0 0 0 0 0 0 0 6.6190 0.1916 -0.0138 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6347 0.6743 -0.8730 C 0 0 1 0 0 0 0 0 0 0 0 0 4.4046 0.6359 -0.1717 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3102 -0.0773 -0.5898 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3870 -0.7362 -1.6488 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0096 -0.1011 0.1778 C 0 0 2 0 0 0 0 0 0 0 0 0 2.2913 -0.6606 1.5818 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1810 -1.8865 1.4744 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4747 -3.0025 0.7425 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6434 -2.4831 -0.3858 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3773 -3.3543 -1.3504 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1274 -1.1147 -0.5049 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2459 -0.9732 -0.0454 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0188 -2.0122 0.1402 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4424 -1.9386 0.6089 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0310 -0.5838 0.4151 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1946 0.3243 -0.4643 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8386 0.3801 0.2222 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0606 1.4526 -0.2444 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4589 1.2706 0.2518 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0000 0.5554 1.7177 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0262 -0.1761 -1.8620 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7755 1.6955 -0.5213 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2327 1.6796 -0.9364 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9565 0.8506 0.1220 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.5113 -0.5787 0.0850 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.8612 -1.2890 -1.1839 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1872 -1.3318 1.2194 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1286 -0.5003 2.0222 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.0981 0.2838 1.1684 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.4224 1.0898 0.1156 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0712 0.9336 -1.2365 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6250 2.5673 0.4966 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8990 1.0341 2.0266 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5131 0.2854 2.9884 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5586 -3.7817 1.6583 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8781 2.0982 -1.2806 C 0 0 1 0 0 0 0 0 0 0 0 0 7.3125 2.3730 -1.6534 C 0 0 2 0 0 0 0 0 0 0 0 0 8.2893 1.6179 -0.8090 C 0 0 2 0 0 0 0 0 0 0 0 0 9.5472 1.6457 -1.4258 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5351 3.7447 -1.4176 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0724 2.4184 -2.3622 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9197 -1.7416 1.4884 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8695 -0.5274 -0.0789 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9068 0.1024 1.3104 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9035 -0.4063 -1.5512 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5903 0.0516 -1.8006 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7554 0.0662 2.2426 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3427 -1.0196 2.0043 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3992 -2.2243 2.4964 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1150 -1.6409 0.9391 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2140 -3.7215 0.3326 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7165 -4.3834 -1.3654 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7809 -3.0517 -2.2003 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2357 -0.8615 -1.6079 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6249 -2.9970 -0.0503 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4236 -2.2808 1.6616 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9909 -2.7401 0.0627 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0038 -0.0900 1.4355 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0824 1.6493 -1.3191 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3081 2.4185 0.2182 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6330 1.6918 1.2862 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0944 1.9617 -0.3855 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0363 0.9682 2.1447 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7284 1.3865 1.9474 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1742 -0.3612 2.2744 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1178 0.3406 -2.2934 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8440 0.1734 -2.5576 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9629 -1.2517 -1.9930 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2397 2.2529 -1.3451 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7038 2.2797 0.3985 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6290 2.7140 -0.8198 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4061 1.3291 -1.9492 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5669 1.2726 1.0969 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1438 -2.0802 -1.4823 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0444 -0.6199 -2.0457 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8368 -1.8534 -1.0630 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7823 -2.2146 0.8390 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4614 -1.7890 1.9295 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7722 -1.2269 2.6044 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7843 -0.4340 0.6583 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4435 1.4067 -2.0007 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0163 1.5539 -1.1997 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4012 -0.0829 -1.4632 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6114 2.6942 1.0035 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5973 3.1857 -0.4003 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8528 2.8589 1.2314 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2947 1.4350 2.6999 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9926 0.2903 3.8463 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9185 -4.4529 1.0706 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1139 -4.2797 2.4703 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8612 -3.0547 2.1678 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5858 2.7778 -0.4428 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5062 2.2147 -2.7413 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3754 2.0802 0.1948 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5328 2.1304 -2.2740 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8836 4.1295 -0.8035 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1902 2.7765 -2.0374 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 1 0 5 6 1 0 6 7 1 0 7 8 2 0 9 7 1 6 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 21 24 1 1 20 25 1 6 20 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 6 29 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 34 36 1 0 33 37 1 0 32 38 1 0 12 39 1 0 5 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 41 44 1 0 40 45 1 0 42 3 1 0 23 9 1 0 34 28 1 0 15 9 1 0 21 16 1 0 29 19 1 0 1 46 1 0 2 47 1 0 2 48 1 0 3 49 1 6 5 50 1 6 10 51 1 0 10 52 1 0 11 53 1 0 11 54 1 0 12 55 1 6 14 56 1 0 14 57 1 0 15 58 1 6 17 59 1 0 18 60 1 0 18 61 1 0 19 62 1 1 22 63 1 0 22 64 1 0 23 65 1 0 23 66 1 0 24 67 1 0 24 68 1 0 24 69 1 0 25 70 1 0 25 71 1 0 25 72 1 0 26 73 1 0 26 74 1 0 27 75 1 0 27 76 1 0 28 77 1 1 30 78 1 0 30 79 1 0 30 80 1 0 31 81 1 0 31 82 1 0 32 83 1 1 33 84 1 6 35 85 1 0 35 86 1 0 35 87 1 0 36 88 1 0 36 89 1 0 36 90 1 0 37 91 1 0 38 92 1 0 39 93 1 0 39 94 1 0 39 95 1 0 40 96 1 1 41 97 1 6 42 98 1 1 43 99 1 0 44100 1 0 45101 1 0 M END

Standard InCHIKey	ONKDPBFYYUGYFL-BBEQLWDVSA-N
Standard InCHI	InChI=1S/C36H56O9/c1-18-10-13-36(31(43)45-30-28(41)27(40)26(39)22(17-37)44-30)15-14-34(6)20(25(36)19(18)2)8-9-24-33(5)16-21(38)29(42)32(3,4)23(33)11-12-35(24,34)7/h8,18,21-30,37-42H,2,9-17H2,1,3-7H3/t18-,21-,22-,23+,24-,25+,26-,27+,28-,29-,30+,33+,34-,35-,36+/m1/s1
SMILES	OC[C@H]1O[C@@H](OC(=O)[C@@]23CC[C@H](C(=C)[C@H]3C3=CC[C@H]4[C@@]([C@@]3(CC2)C)(C)CC[C@@H]2[C@]4(C)C[C@H]([C@H](C2(C)C)O)O)C)[C@@H]([C@H]([C@@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	632.39	Volume:	651.076 ? Van der Waals volume.
Dense:	0.971	LogP:	2.83 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.142 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.732 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	34.0
TPSA:	156.91 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	6.0	Rings:	6.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.203	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.61	Fsp³:	0.861
MCE-18:	127.672 ? 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:	0.858	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.102 ? 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:	0.161	Promiscuous compounds:	0.171

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.759	MDCK Permeability:	-5.096
Pgp-inhibitor:	0.002	Pgp-substrate:	0.013
PAMPA:	0.999 ? 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%):	0.215	30% Bioavailability (F30%):	0.941
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.212
Plasma Protein Binding (PPB):	85.366%	Volume Distribution (VD):	0.081
Fu:	13.527% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.761
BSEP inhibitor:	0.903

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.02
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.658
HLM stability:	0.012 ? 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):

1.929

Half-life (T1/2):

2.775

ADMET: Toxicity

hERG Blockers:	0.004	hERG Blockers (10um):	0.019
Human Hepatotoxicity (H-HT):	0.459	Drug-induced Liver Injury (DILI):	0.28
AMES Toxicity:	0.665	Rat Oral Acute Toxicity:	0.01
Maximum Recommended Daily Dose:	0.066	Skin Sensitization:	0.996
Carcinogencity:	0.522	Eye Corrosion:	0.0
Eye Irritation:	0.01	Respiratory Toxicity:	0.041
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.987
Hematotoxicity:	0.559	Drug-induced Nephrotoxicity:	0.95
Genotoxicity:	0.11	RPMI-8226 Immunitoxicity:	0.048
A549 Cytotoxicity:	0.501	Hek293 Cytotoxicity:	0.139
BCF:	1.593 ? 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:	3.964 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.639 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.854 ? 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
NPO23655.1	Rubus ellipticus	Under-species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[19795885]
NPO23655.1	Rubus ellipticus	Under-species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[38455614]
NPO60488	Anthyllis henoniana	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39061863]
NPO23655.1	Rubus ellipticus	Under-species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]

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
NPO60488	Anthyllis henoniana	Methanol extract	Stems	1.6	n.a.	n.a.	%	PMID[39061863]

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	1

Activity Type	# Activity
Others	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
NPT2	Others	Unspecified	n.a.	IC50	=	1040000.0	nM	PMID[21142180]

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 NPC75747 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	20870
0.1-0.2	23587
0.2-0.3	4288
0.3-0.4	895
0.4-0.5	145
0.5-0.6	50
0.6-0.7	13
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC7870
0.8831	High Similarity	NPC102914
0.7848	Intermediate Similarity	NPC605954
0.7778	Intermediate Similarity	NPC310014
0.7778	Intermediate Similarity	NPC269315
0.7176	Intermediate Similarity	NPC220984
0.6905	Remote Similarity	NPC116794
0.686	Remote Similarity	NPC271138
0.686	Remote Similarity	NPC110139
0.686	Remote Similarity	NPC108709
0.6824	Remote Similarity	NPC65590
0.6824	Remote Similarity	NPC125923
0.6744	Remote Similarity	NPC68419
0.6429	Remote Similarity	NPC191763
0.6395	Remote Similarity	NPC46388
0.6279	Remote Similarity	NPC167383
0.618	Remote Similarity	NPC137917
0.6	Remote Similarity	NPC212968
0.6	Remote Similarity	NPC604133
0.5889	Remote Similarity	NPC37739
0.5889	Remote Similarity	NPC199457
0.5789	Remote Similarity	NPC269095
0.5778	Remote Similarity	NPC237503
0.5729	Remote Similarity	NPC78046
0.567	Remote Similarity	NPC179434
0.5652	Remote Similarity	NPC187056
0.5652	Remote Similarity	NPC606216
0.5652	Remote Similarity	NPC607023
0.5521	Remote Similarity	NPC47063
0.5474	Remote Similarity	NPC128925
0.5474	Remote Similarity	NPC256798
0.5464	Remote Similarity	NPC204458
0.5464	Remote Similarity	NPC189884
0.5464	Remote Similarity	NPC138334
0.5422	Remote Similarity	NPC259788
0.5422	Remote Similarity	NPC255589
0.5422	Remote Similarity	NPC307335
0.5422	Remote Similarity	NPC74855
0.54	Remote Similarity	NPC139894
0.5347	Remote Similarity	NPC150400
0.5319	Remote Similarity	NPC48249
0.5319	Remote Similarity	NPC64106
0.5306	Remote Similarity	NPC90856
0.5306	Remote Similarity	NPC214484
0.5301	Remote Similarity	NPC136313
0.5275	Remote Similarity	NPC91583
0.5258	Remote Similarity	NPC209894
0.5253	Remote Similarity	NPC29069
0.5243	Remote Similarity	NPC473343
0.5234	Remote Similarity	NPC134835
0.5213	Remote Similarity	NPC306746
0.52	Remote Similarity	NPC48499
0.5196	Remote Similarity	NPC58448
0.5185	Remote Similarity	NPC73318
0.5161	Remote Similarity	NPC285576
0.5146	Remote Similarity	NPC39211
0.5106	Remote Similarity	NPC190837
0.5098	Remote Similarity	NPC235405
0.5098	Remote Similarity	NPC475516
0.5096	Remote Similarity	NPC161674
0.5096	Remote Similarity	NPC475171
0.5096	Remote Similarity	NPC469946
0.5091	Remote Similarity	NPC96641
0.5091	Remote Similarity	NPC163183
0.5049	Remote Similarity	NPC473373
0.5049	Remote Similarity	NPC249848
0.5049	Remote Similarity	NPC107966
0.5048	Remote Similarity	NPC75417
0.5047	Remote Similarity	NPC68175

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC75747 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7421
0.1-0.2	1658
0.2-0.3	68
0.3-0.4	3
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