NPASS Compound

Natural Product: NPC469397

Natural Product ID	NPC469397
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	TUUZZRKOUMSRMU-ZHNAOBHOSA-N
IUPAC Name	n.a.
Synonyms	6'-O-Vanillylpaeoniflorin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1077644
PubChem CID	46882881
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0002049] Terpene 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 2D 80 86 0 0 0 0 0 0 0 0999 V2000 -6.3826 -1.6620 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2169 -2.6060 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4516 -4.0876 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2858 -5.0315 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5205 -6.5131 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3548 -7.4571 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1890 -8.4010 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7887 -7.8635 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6117 -7.3259 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1609 -6.0402 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5664 -4.7282 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8010 -3.2467 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3647 -2.3027 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1147 -3.6018 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4138 -2.8518 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6638 -1.5527 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0641 -1.0152 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4645 -0.4776 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6991 1.0039 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5334 1.9479 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0995 1.5415 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3342 3.0230 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7345 3.5605 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.9003 2.6166 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6656 1.1350 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2652 0.5975 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -1.2990 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 -2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 1.2990 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 2.5981 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0661 -4.7021 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8387 -5.9878 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1115 -7.2997 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8768 -8.7813 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0044 -6.9318 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4665 -4.1645 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9209 -7.0506 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0866 -6.1066 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8519 -4.6251 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0176 -3.6811 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6547 -0.8672 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4386 -0.4963 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3266 -2.8278 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8855 -4.4940 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4108 -6.2913 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2987 -8.6228 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2511 -9.2639 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3262 -6.4631 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8979 -8.7984 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4141 -4.6425 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8647 -4.9008 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5413 -4.1556 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8045 -3.4137 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7684 -2.3396 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7013 0.4403 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1685 3.9670 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9692 5.0421 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3006 3.1541 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.8313 0.1910 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2129 -0.9016 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9888 0.1828 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4028 -3.7960 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8808 -2.0120 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4210 -3.6401 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 0.9642 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7580 -0.8169 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 3.8971 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3267 -3.2249 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0823 -5.1491 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5297 -7.7881 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0425 -9.7253 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4048 -6.3942 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7386 -4.9594 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1555 -8.5322 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4869 -6.6442 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4180 -4.2187 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 13 12 1 1 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 6 17 18 1 0 18 19 1 0 19 20 2 0 19 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 16 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 32 34 1 1 11 35 1 0 35 36 1 0 36 37 1 0 37 38 1 0 36 39 1 0 35 40 1 0 5 41 2 0 41 42 1 0 42 43 2 0 43 44 1 0 43 3 1 0 37 9 1 0 29 13 1 0 16 13 1 0 26 21 1 0 33 27 1 0 32 15 1 0 1 45 1 0 1 46 1 0 1 47 1 0 4 48 1 0 6 49 1 0 6 50 1 0 8 51 1 0 8 52 1 0 9 53 1 6 11 54 1 6 14 55 1 0 14 56 1 0 15 57 1 6 17 58 1 0 17 59 1 0 22 60 1 0 23 61 1 0 24 62 1 0 25 63 1 0 26 64 1 0 27 65 1 6 30 66 1 0 30 67 1 0 30 68 1 0 31 69 1 0 31 70 1 0 34 71 1 0 35 72 1 1 36 73 1 6 37 74 1 1 38 75 1 0 39 76 1 0 40 77 1 0 41 78 1 0 42 79 1 0 44 80 1 0 M END

Standard InCHIKey	TUUZZRKOUMSRMU-ZHNAOBHOSA-N
Standard InCHI	InChI=1S/C31H36O13/c1-28-14-30(37)21-11-31(28,29(21,27(43-28)44-30)15-40-25(36)17-6-4-3-5-7-17)42-26-24(35)23(34)22(33)20(41-26)13-39-12-16-8-9-18(32)19(10-16)38-2/h3-10,20-24,26-27,32-35,37H,11-15H2,1-2H3/t20-,21+,22-,23+,24-,26+,27-,28+,29+,30-,31-/m1/s1
SMILES	COc1cc(COC[C@H]2O[C@@H](O[C@]34C[C@H]5[C@@]4(COC(=O)c4ccccc4)[C@@H]4O[C@@]3(C)C[C@]5(O4)O)[C@@H]([C@H]([C@@H]2O)O)O)ccc1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	616.22	Volume:	580.655 ? Van der Waals volume.
Dense:	1.061	LogP:	1.28 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.626 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.705 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	32.0
TPSA:	182.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	5.0	Rings:	9.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.234	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.232	Fsp³:	0.581
MCE-18:	158.878 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.594	Fluc inhibitor:	0.081 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.02 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.215 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.027	Promiscuous compounds:	0.188

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.906	MDCK Permeability:	-5.211
Pgp-inhibitor:	0.037	Pgp-substrate:	0.115
PAMPA:	0.968 ? 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):	0.077
20% Bioavailability (F20%):	0.028	30% Bioavailability (F30%):	0.641
50% Bioavailability (F50%):	0.65

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.016	MRP1:	0.715
Plasma Protein Binding (PPB):	65.181%	Volume Distribution (VD):	-0.588
Fu:	44.53% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.123
BSEP inhibitor:	0.871

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.12
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.009
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.01
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.993
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.133 ? 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):

2.115

Half-life (T1/2):

3.145

ADMET: Toxicity

hERG Blockers:	0.102	hERG Blockers (10um):	0.739
Human Hepatotoxicity (H-HT):	0.251	Drug-induced Liver Injury (DILI):	0.216
AMES Toxicity:	0.727	Rat Oral Acute Toxicity:	0.186
Maximum Recommended Daily Dose:	0.371	Skin Sensitization:	0.986
Carcinogencity:	0.059	Eye Corrosion:	0.0
Eye Irritation:	0.055	Respiratory Toxicity:	0.599
Drug-induced Neurotoxicity:	0.04	Ototoxicity:	0.721
Hematotoxicity:	0.363	Drug-induced Nephrotoxicity:	0.745
Genotoxicity:	0.082	RPMI-8226 Immunitoxicity:	0.26
A549 Cytotoxicity:	0.079	Hek293 Cytotoxicity:	0.337
BCF:	0.638 ? 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:	3.577 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.327 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.498 ? 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
NPO22550	Paeonia suffruticosa	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11339628]
NPO22550	Paeonia suffruticosa	Species	Paeoniaceae	Eukaryota	n.a.	bark	n.a.	PMID[17260795]
NPO22550	Paeonia suffruticosa	Species	Paeoniaceae	Eukaryota	n.a.	Daejeon, Korea	2007-Jan	PMID[19670875]
NPO30226	Paeonia albiflora	Species	Paeoniaceae	Eukaryota	roots	n.a.	n.a.	PMID[19691309]
NPO22550	Paeonia suffruticosa	Species	Paeoniaceae	Eukaryota	n.a.	seed	n.a.	PMID[20822014]
NPO22550	Paeonia suffruticosa	Species	Paeoniaceae	Eukaryota	n.a.	root	n.a.	PMID[22547314]
NPO22550	Paeonia suffruticosa	Species	Paeoniaceae	Eukaryota	root bark	Bozhou, Anhui Province, China	2010-AUG	PMID[24377852]
NPO22550	Paeonia suffruticosa	Species	Paeoniaceae	Eukaryota	n.a.	flower	n.a.	PMID[24504864]
NPO22550	Paeonia suffruticosa	Species	Paeoniaceae	Eukaryota	Flowers	LuoYang, HeNan, China	n.a.	PMID[24621197]
NPO30226	Paeonia albiflora	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22550	Paeonia suffruticosa	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30226	Paeonia albiflora	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22550	Paeonia suffruticosa	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22550	Paeonia suffruticosa	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO30226	Paeonia albiflora	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO22550	Paeonia suffruticosa	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO22550	Paeonia suffruticosa	Species	Paeoniaceae	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
Inhibition	4
IC50	1
INH	2

Activity Type	# Activity
Cell line	5
Others	2

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
NPT848	Cell line	N9	Homo sapiens	Inhibition	=	107.1	%	PubChem BioAssay data set
NPT848	Cell line	N9	Homo sapiens	Inhibition	=	106.3	%	PMID[24582402]
NPT848	Cell line	N9	Homo sapiens	Inhibition	=	99.8	%	PubChem BioAssay data set
NPT848	Cell line	N9	Homo sapiens	Inhibition	=	90.1	%	PMID[16643031]
NPT848	Cell line	N9	Homo sapiens	IC50	>	100000.0	nM	PMID[15921415]
NPT610	Others	Molecular identity unknown	n.a.	INH	=	2.78	mM	PMID[24377852]
NPT610	Others	Molecular identity unknown	n.a.	INH	=	2.02	mM	PMID[24377852]

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 NPC469397 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	11488
0.1-0.2	34371
0.2-0.3	3805
0.3-0.4	149
0.4-0.5	15
0.5-0.6	7
0.6-0.7	15
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8404	Intermediate Similarity	NPC188217
0.7368	Intermediate Similarity	NPC469396
0.7368	Intermediate Similarity	NPC469458
0.7368	Intermediate Similarity	NPC149002
0.7363	Intermediate Similarity	NPC34066
0.7363	Intermediate Similarity	NPC190862
0.7071	Intermediate Similarity	NPC148185
0.7041	Intermediate Similarity	NPC80360
0.6947	Remote Similarity	NPC88176
0.6837	Remote Similarity	NPC469398
0.6768	Remote Similarity	NPC469438
0.6596	Remote Similarity	NPC303429
0.6596	Remote Similarity	NPC56594
0.6471	Remote Similarity	NPC195114
0.6381	Remote Similarity	NPC478828
0.6355	Remote Similarity	NPC469421
0.6355	Remote Similarity	NPC478829
0.6327	Remote Similarity	NPC120012
0.6296	Remote Similarity	NPC478826
0.6296	Remote Similarity	NPC478827
0.6224	Remote Similarity	NPC293568
0.6224	Remote Similarity	NPC161626
0.6055	Remote Similarity	NPC477617
0.5545	Remote Similarity	NPC469417
0.5524	Remote Similarity	NPC469419
0.5446	Remote Similarity	NPC469448
0.5437	Remote Similarity	NPC469422
0.537	Remote Similarity	NPC469418
0.5273	Remote Similarity	NPC260300
0.5185	Remote Similarity	NPC469420

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC469397 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3549
0.1-0.2	5488
0.2-0.3	112
0.3-0.4	0
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