NPASS Compound

Natural Product: NPC475482

Natural Product ID	NPC475482
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(1S,2R,4As,6Ar,6Ar,6Br,8Ar,9R,10S,12Ar,14Bs)-10-Hydroxy-9-(Hydroxymethyl)-6A-[[(Z)-3-(4-Hydroxyphenyl)Prop-2-Enoyl]Oxymethyl]-1,2,6B,9,12A-Pentamethyl-2,3,4,5,6,6A,7,8,8A,10,11,12,13,14B-Tetradecahydro-1H-Picene-4A-Carboxylic Acid
IUPAC Name	(1S,2R,4aS,6aR,6aR,6bR,8aR,9R,10S,12aR,14bS)-10-hydroxy-9-(hydroxymethyl)-6a-[[(Z)-3-(4-hydroxyphenyl)prop-2-enoyl]oxymethyl]-1,2,6b,9,12a-pentamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL506421
PubChem CID	44566351
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids

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 100105 0 0 0 0 0 0 0 0999 V2000 -3.6429 4.5215 -0.3085 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6929 3.8263 -0.8765 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8556 2.4664 -0.1695 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.9920 1.7782 -0.8307 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2358 2.7464 1.2567 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.3227 1.9488 1.6914 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1004 2.7414 2.2096 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1244 1.6605 2.1136 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2137 0.8198 0.8219 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5227 1.7956 -0.2687 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1862 1.3746 -1.6534 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6983 0.9851 -1.6515 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5257 -0.2137 -0.7377 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7937 0.3315 0.6293 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3248 -0.4420 1.7846 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4702 -1.6000 1.4234 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1247 -1.7833 0.2414 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0865 -0.7368 -0.8000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8418 0.4108 -0.4409 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1969 -0.0130 -0.5049 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2454 0.8917 -0.2125 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8006 2.0246 0.0851 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6027 0.4751 -0.2761 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6530 1.1850 -0.1018 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6700 2.5877 0.1794 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6931 3.0131 1.0491 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8979 4.3286 1.3055 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1418 5.3377 0.7509 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1421 4.9510 -0.0996 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9268 3.5887 -0.3698 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4149 6.6542 1.0658 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3293 -1.2380 -2.1309 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3612 -2.6885 -2.3816 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6031 -3.6187 -1.2591 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9180 -3.0223 0.0671 C 0 0 1 0 0 0 0 0 0 0 0 0 2.3746 -2.9289 0.4018 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5545 -2.2735 1.7428 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8504 -4.3820 0.6393 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2073 -5.3077 -0.3547 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7945 -4.5452 -1.5933 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3542 -4.4588 0.4376 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5264 -4.5823 -1.0649 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1733 -4.6479 -0.0017 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8596 -5.4257 -2.1019 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4112 -1.2895 -1.2213 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1995 -0.2426 1.0966 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9039 5.2599 0.2706 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5722 3.7334 -1.9525 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6102 4.4439 -0.6641 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7557 1.3943 -0.0904 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7267 0.9493 -1.5067 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6028 2.4807 -1.4757 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6842 3.7868 1.2952 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1773 1.7390 2.6431 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5977 3.7526 2.1403 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5467 2.7541 3.2488 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2418 0.9403 2.9770 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0979 2.0788 2.2524 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7766 2.6345 -0.0620 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1906 2.3081 -2.2930 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8185 0.6724 -2.1463 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2585 1.8930 -1.1319 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3153 0.8619 -2.6566 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2159 1.3095 0.6546 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7027 0.2047 2.4727 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1219 -0.8309 2.4530 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3291 -2.3459 2.1996 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7019 0.7510 0.6081 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7849 1.2375 -1.1756 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7813 -0.5992 -0.5047 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6727 0.6862 -0.1780 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3381 2.2549 1.5296 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7092 4.6036 1.9914 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5346 5.7143 -0.5485 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1654 3.4182 -1.1164 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3288 7.0318 0.7871 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3694 -0.8467 -2.3844 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2540 -0.7817 -2.9925 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1394 -2.9064 -3.1794 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5635 -3.0741 -2.9193 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5518 -3.7984 0.8306 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0339 -2.5753 -0.3834 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6316 -1.9356 1.7940 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9397 -1.3807 1.8895 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4320 -2.9914 2.5819 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6217 -4.7183 1.6510 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3234 -5.8453 0.0545 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9352 -6.0700 -0.6653 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6399 -3.9613 -1.9898 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5080 -5.2895 -2.3621 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5668 -4.7439 -0.6276 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8391 -5.1844 1.1044 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8169 -3.4644 0.6027 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6585 -6.0466 -2.1104 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4889 -1.0972 -1.2156 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2376 -2.2033 -0.6474 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1821 -1.4265 -2.3215 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7504 -1.2818 1.1422 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0558 -0.3147 0.4155 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6691 -0.1854 2.1301 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 3 2 1 6 3 4 1 0 3 5 1 0 5 6 1 0 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 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 2 0 17 18 1 0 18 19 1 1 19 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 28 31 1 0 18 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 36 38 1 0 38 39 1 0 39 40 1 0 38 41 1 0 34 42 1 1 42 43 2 0 42 44 1 0 13 45 1 6 9 46 1 1 10 3 1 0 18 13 1 0 30 25 1 0 40 34 1 0 14 9 1 0 35 17 1 0 1 47 1 0 2 48 1 0 2 49 1 0 4 50 1 0 4 51 1 0 4 52 1 0 5 53 1 6 6 54 1 0 7 55 1 0 7 56 1 0 8 57 1 0 8 58 1 0 10 59 1 1 11 60 1 0 11 61 1 0 12 62 1 0 12 63 1 0 14 64 1 6 15 65 1 0 15 66 1 0 16 67 1 0 19 68 1 0 19 69 1 0 23 70 1 0 24 71 1 0 26 72 1 0 27 73 1 0 29 74 1 0 30 75 1 0 31 76 1 0 32 77 1 0 32 78 1 0 33 79 1 0 33 80 1 0 35 81 1 1 36 82 1 6 37 83 1 0 37 84 1 0 37 85 1 0 38 86 1 1 39 87 1 0 39 88 1 0 40 89 1 0 40 90 1 0 41 91 1 0 41 92 1 0 41 93 1 0 44 94 1 0 45 95 1 0 45 96 1 0 45 97 1 0 46 98 1 0 46 99 1 0 46100 1 0 M END

Standard InCHIKey	UQWOVDOTSQPRJO-RBHNILKQSA-N
Standard InCHI	InChI=1S/C39H54O7/c1-24-14-19-38(34(44)45)20-21-39(23-46-32(43)13-8-26-6-9-27(41)10-7-26)28(33(38)25(24)2)11-12-30-35(3)17-16-31(42)36(4,22-40)29(35)15-18-37(30,39)5/h6-11,13,24-25,29-31,33,40-42H,12,14-23H2,1-5H3,(H,44,45)/b13-8-/t24-,25+,29-,30-,31+,33+,35+,36+,37-,38+,39+/m1/s1
SMILES	OC[C@]1(C)[C@@H](O)CC[C@]2([C@H]1CC[C@@]1([C@@H]2CC=C2[C@@]1(COC(=O)/C=Cc1ccc(cc1)O)CC[C@@]1([C@H]2[C@@H](C)[C@@H](CC1)C)C(=O)O)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	634.39	Volume:	674.838 ? Van der Waals volume.
Dense:	0.94	LogP:	4.034 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.57 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.129 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	35.0
TPSA:	124.29 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	4.0	Rings:	6.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.151	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.17	Fsp³:	0.692
MCE-18:	158.667 ? 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:	0.971	Fluc inhibitor:	0.973 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.083 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.011 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.099	Promiscuous compounds:	0.053

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.701	MDCK Permeability:	-5.175
Pgp-inhibitor:	0.02	Pgp-substrate:	0.0
PAMPA:	1.0 ? 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):	0.011
20% Bioavailability (F20%):	0.993	30% Bioavailability (F30%):	0.427
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.015	MRP1:	0.245
Plasma Protein Binding (PPB):	95.101%	Volume Distribution (VD):	-0.5
Fu:	2.644% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.143	BCRP inhibitor:	0.018
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.005	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.499
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.19
HLM stability:	0.0 ? 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):

1.651

Half-life (T1/2):

1.826

ADMET: Toxicity

hERG Blockers:	0.061	hERG Blockers (10um):	0.063
Human Hepatotoxicity (H-HT):	0.681	Drug-induced Liver Injury (DILI):	0.155
AMES Toxicity:	0.309	Rat Oral Acute Toxicity:	0.15
Maximum Recommended Daily Dose:	0.562	Skin Sensitization:	0.999
Carcinogencity:	0.561	Eye Corrosion:	0.0
Eye Irritation:	0.227	Respiratory Toxicity:	0.796
Drug-induced Neurotoxicity:	0.061	Ototoxicity:	0.682
Hematotoxicity:	0.13	Drug-induced Nephrotoxicity:	0.877
Genotoxicity:	0.55	RPMI-8226 Immunitoxicity:	0.042
A549 Cytotoxicity:	0.871	Hek293 Cytotoxicity:	0.638
BCF:	0.67 ? 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:	3.912 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.46 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.819 ? 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
NPO33035	ilex kudincha	Species	Aquifoliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10425145]
NPO33035	ilex kudincha	Species	Aquifoliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10479318]

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	1

Activity Type	# Activity
Individual protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT3065	Individual protein	Acyl coenzyme A:cholesterol acyltransferase 1	Rattus norvegicus	IC50	=	194000.0	nM	PMID[23571415]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

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 NPC475482 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	7745
0.1-0.2	36199
0.2-0.3	5239
0.3-0.4	525
0.4-0.5	98
0.5-0.6	30
0.6-0.7	14
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	2
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.907	High Similarity	NPC54627
0.907	High Similarity	NPC249817
0.7812	Intermediate Similarity	NPC310729
0.7812	Intermediate Similarity	NPC150310
0.734	Intermediate Similarity	NPC262970
0.7113	Intermediate Similarity	NPC479747
0.7113	Intermediate Similarity	NPC479746
0.6907	Remote Similarity	NPC479744
0.6633	Remote Similarity	NPC198621
0.6633	Remote Similarity	NPC216940
0.6436	Remote Similarity	NPC178093
0.6429	Remote Similarity	NPC475457
0.6346	Remote Similarity	NPC206232
0.6346	Remote Similarity	NPC14515
0.6337	Remote Similarity	NPC304110
0.6337	Remote Similarity	NPC27518
0.6337	Remote Similarity	NPC611516
0.6095	Remote Similarity	NPC479740
0.6095	Remote Similarity	NPC479741
0.6058	Remote Similarity	NPC473773
0.6058	Remote Similarity	NPC475579
0.5962	Remote Similarity	NPC479739
0.5962	Remote Similarity	NPC482049
0.5962	Remote Similarity	NPC482050
0.5909	Remote Similarity	NPC61543
0.5909	Remote Similarity	NPC293048
0.5909	Remote Similarity	NPC225585
0.5865	Remote Similarity	NPC606782
0.5849	Remote Similarity	NPC479745
0.5701	Remote Similarity	NPC475454
0.5701	Remote Similarity	NPC473579
0.5607	Remote Similarity	NPC324798
0.5607	Remote Similarity	NPC479742
0.5506	Remote Similarity	NPC274330
0.5495	Remote Similarity	NPC118033
0.5472	Remote Similarity	NPC172311
0.5472	Remote Similarity	NPC482052
0.5398	Remote Similarity	NPC53520
0.5333	Remote Similarity	NPC271494
0.5283	Remote Similarity	NPC22676
0.5278	Remote Similarity	NPC25491
0.5275	Remote Similarity	NPC51700
0.5275	Remote Similarity	NPC88716
0.5275	Remote Similarity	NPC68160
0.5243	Remote Similarity	NPC485587
0.5238	Remote Similarity	NPC475627
0.5192	Remote Similarity	NPC173569
0.5185	Remote Similarity	NPC605663
0.5182	Remote Similarity	NPC472801
0.5146	Remote Similarity	NPC478270
0.5146	Remote Similarity	NPC478271

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475482 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3542
0.1-0.2	5500
0.2-0.3	103
0.3-0.4	4
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
0.5865	Remote Similarity	NPD8166	Discontinued

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