NPASS Compound

Natural Product: NPC256776

Natural Product ID	NPC256776
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Kadsuranin
IUPAC Name	n.a.
Synonyms	Kadsuranin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL513752
PubChem CID	174277
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000238] Tannins [CHEMONTID:0001710] Hydrolyzable tannins

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 57 60 0 0 0 0 0 0 0 0999 V2000 -2.3998 -4.6947 0.3250 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7954 -3.3830 0.5991 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9225 -2.3325 0.3708 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6543 -2.5719 -0.1293 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1996 -1.5551 -0.3568 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5033 -2.0609 -0.8544 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5149 -0.9372 -0.9155 C 0 0 2 0 0 0 0 0 0 0 0 0 3.6628 -1.4906 -1.7422 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0498 -0.4328 0.3491 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6830 -1.2851 1.5687 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8017 0.9963 0.7193 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5966 1.5912 0.1140 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3574 1.0639 -0.2502 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2508 -0.2619 -0.0680 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4917 0.0392 0.4347 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3431 -1.0196 0.6544 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5999 -0.7909 1.1496 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8232 -0.7811 2.5619 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7720 1.3634 0.6921 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5366 1.9839 1.9420 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6510 1.7761 -0.8550 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8075 1.0985 -1.1770 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0165 0.4703 -2.4284 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3976 3.1058 -1.0986 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8262 3.6825 -0.7491 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8003 2.9178 -0.1520 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8012 5.0154 -1.1067 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5324 5.3496 -1.4950 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1802 4.1100 -1.6804 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3220 -5.3275 0.2982 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9749 -4.7509 -0.6982 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6857 -5.0932 1.0669 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3090 -3.5858 -0.3534 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3043 -2.4552 -1.8823 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8611 -2.8356 -0.1804 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1266 -0.0743 -1.5125 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5110 -0.7872 -1.8014 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3182 -1.8226 -2.7519 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9797 -2.4340 -1.2221 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1802 -0.5388 0.3169 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9894 -2.3441 1.4338 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3170 -0.9282 2.4318 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6459 -1.2024 1.8716 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6740 1.6067 0.3941 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7367 1.0705 1.8236 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8284 -1.1813 2.8174 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7663 0.2829 2.8775 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0129 -1.3163 3.1019 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9787 1.3375 2.6182 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9272 2.8859 1.7450 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4874 2.3835 2.3776 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9082 0.8879 -2.9409 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0888 0.5857 -3.0086 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2365 -0.5960 -2.2380 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7633 3.3519 0.1254 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9951 5.9637 -0.7012 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5085 5.9502 -2.4316 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 7 9 1 0 9 10 1 0 9 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 15 19 1 0 19 20 1 0 13 21 1 0 21 22 1 0 22 23 1 0 21 24 2 0 24 25 1 0 25 26 2 0 25 27 1 0 27 28 1 0 28 29 1 0 16 3 1 0 29 24 1 0 14 5 2 0 26 12 1 0 1 30 1 0 1 31 1 0 1 32 1 0 4 33 1 0 6 34 1 0 6 35 1 0 7 36 1 6 8 37 1 0 8 38 1 0 8 39 1 0 9 40 1 6 10 41 1 0 10 42 1 0 10 43 1 0 11 44 1 0 11 45 1 0 18 46 1 0 18 47 1 0 18 48 1 0 20 49 1 0 20 50 1 0 20 51 1 0 23 52 1 0 23 53 1 0 23 54 1 0 26 55 1 0 28 56 1 0 28 57 1 0 M END

Standard InCHIKey	RTZKSTLPRTWFEV-QWHCGFSZSA-N
Standard InCHI	InChI=1S/C23H28O6/c1-12-7-14-9-16(24-3)20(25-4)22(26-5)18(14)19-15(8-13(12)2)10-17-21(23(19)27-6)29-11-28-17/h9-10,12-13H,7-8,11H2,1-6H3/t12-,13+/m0/s1
SMILES	COc1cc2C[C@H](C)[C@H](C)Cc3c(c2c(c1OC)OC)c(OC)c1c(c3)OCO1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	400.19	Volume:	409.061 ? Van der Waals volume.
Dense:	0.978	LogP:	3.157 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.12 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.458 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	22.0
TPSA:	55.38 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.754	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.534	Fsp³:	0.478
MCE-18:	79.059 ? 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:	0.699	Fluc inhibitor:	0.339 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.525 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.149 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.308	Promiscuous compounds:	0.475

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.732	MDCK Permeability:	-4.664
Pgp-inhibitor:	0.293	Pgp-substrate:	0.031
PAMPA:	0.015 ? 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%):	0.003	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.177

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.666	MRP1:	0.989
Plasma Protein Binding (PPB):	89.206%	Volume Distribution (VD):	0.064
Fu:	9.131% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.919
OATP1B3 inhibitor:	0.901	BCRP inhibitor:	0.009
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.553
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.981
CYP2C9-inhibitor:	0.981	CYP2C9-substrate:	0.982
CYP2D6-inhibitor:	0.977	CYP2D6-substrate:	0.995
CYP3A4-inhibitor:	0.996	CYP3A4-substrate:	0.994
CYP2B6-substrate:	0.983	CYP2C8-inhibitor:	0.186
HLM stability:	0.652 ? 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):

4.982

Half-life (T1/2):

0.559

ADMET: Toxicity

hERG Blockers:	0.137	hERG Blockers (10um):	0.461
Human Hepatotoxicity (H-HT):	0.542	Drug-induced Liver Injury (DILI):	0.692
AMES Toxicity:	0.573	Rat Oral Acute Toxicity:	0.283
Maximum Recommended Daily Dose:	0.423	Skin Sensitization:	0.489
Carcinogencity:	0.897	Eye Corrosion:	0.036
Eye Irritation:	0.853	Respiratory Toxicity:	0.835
Drug-induced Neurotoxicity:	0.54	Ototoxicity:	0.468
Hematotoxicity:	0.691	Drug-induced Nephrotoxicity:	0.489
Genotoxicity:	0.019	RPMI-8226 Immunitoxicity:	0.162
A549 Cytotoxicity:	0.422	Hek293 Cytotoxicity:	0.446
BCF:	2.649 ? 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:	4.58 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.054 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.558 ? 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
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16562834]
NPO7385	Schisandra sphenanthera	Species	Schisandraceae	Eukaryota	fruits	n.a.	n.a.	PMID[23265871]
NPO29191	Schisandra neglecta	Species	Schisandraceae	Eukaryota	Stems	Luoji Mountain Village, Xichang County, Sicuan Province, China	2011-Sep	PMID[23738539]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	fruit	n.a.	PMID[24155209]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24959987]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25302569]
NPO25811	Euphorbia erythraea	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25648	Gnaphalium liebmannii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26233	Helenium autumnale	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26046	Pseudogynoxys engleri	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25917	Sorghum sativum	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23979	Synadenium compactum	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16407	Tinospora tuberculata	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7385	Schisandra sphenanthera	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25679	Aloe rubroviolacea	Species	Asphodelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25539	Alternaria mali	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO225	Eupatorium angustifolium	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7385	Schisandra sphenanthera	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26233	Helenium autumnale	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26233	Helenium autumnale	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7385	Schisandra sphenanthera	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7385	Schisandra sphenanthera	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO26233	Helenium autumnale	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7385	Schisandra sphenanthera	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO225	Eupatorium angustifolium	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26233	Helenium autumnale	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25811	Euphorbia erythraea	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25917	Sorghum sativum	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16407	Tinospora tuberculata	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29191	Schisandra neglecta	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25648	Gnaphalium liebmannii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25679	Aloe rubroviolacea	Species	Asphodelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25539	Alternaria mali	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7385	Schisandra sphenanthera	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23979	Synadenium compactum	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO26046	Pseudogynoxys engleri	Species	Asteraceae	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
Activity	5
EC50	1
IC50	2
Inhibition	2

Activity Type	# Activity
Individual protein	3
Non-molecular	1
Organism	2
Others	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	-5.94	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT591	Individual protein	Glycogen synthase kinase-3 beta	Homo sapiens	IC50	=	81.0	nM	PMID[35390715]
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	-24.04	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1114	Organism	Human immunodeficiency virus	Human immunodeficiency virus	EC50	=	0.8	ug.mL-1	PMID[14987069]
NPT1114	Organism	Human immunodeficiency virus	Human immunodeficiency virus	IC50	=	2000.0	nM	PMID[9834179]
NPT2	Others	Unspecified	n.a.	Activity	=	100.0	%	PMID[25302569]
NPT2	Others	Unspecified	n.a.	Activity	=	152.0	%	PMID[25302569]
NPT2	Others	Unspecified	n.a.	Activity	=	97.0	%	PMID[25302569]
NPT2	Others	Unspecified	n.a.	Activity	=	81.0	%	PMID[25302569]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	106.0	%	PMID[25302569]

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 NPC256776 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	25872
0.1-0.2	21678
0.2-0.3	1879
0.3-0.4	257
0.4-0.5	102
0.5-0.6	40
0.6-0.7	12
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC145722
1.0	High Similarity	NPC185680
0.9459	High Similarity	NPC32189
0.7838	Intermediate Similarity	NPC283114
0.7838	Intermediate Similarity	NPC207702
0.7838	Intermediate Similarity	NPC149008
0.75	Intermediate Similarity	NPC220577
0.7347	Intermediate Similarity	NPC230538
0.7347	Intermediate Similarity	NPC229172
0.7347	Intermediate Similarity	NPC103637
0.7347	Intermediate Similarity	NPC36531
0.7083	Intermediate Similarity	NPC53722
0.7083	Intermediate Similarity	NPC201404
0.7083	Intermediate Similarity	NPC290714
0.7059	Intermediate Similarity	NPC76415
0.7059	Intermediate Similarity	NPC218510
0.6939	Remote Similarity	NPC172171
0.6939	Remote Similarity	NPC239254
0.6939	Remote Similarity	NPC133934
0.6744	Remote Similarity	NPC87295
0.6667	Remote Similarity	NPC304821
0.66	Remote Similarity	NPC184684
0.66	Remote Similarity	NPC184641
0.6102	Remote Similarity	NPC473323
0.6071	Remote Similarity	NPC166506
0.6071	Remote Similarity	NPC110763
0.6071	Remote Similarity	NPC85141
0.6	Remote Similarity	NPC473425
0.5957	Remote Similarity	NPC216434
0.5957	Remote Similarity	NPC103448
0.5957	Remote Similarity	NPC606558
0.5833	Remote Similarity	NPC324962
0.58	Remote Similarity	NPC141493
0.5763	Remote Similarity	NPC191352
0.5714	Remote Similarity	NPC206737
0.5714	Remote Similarity	NPC289258
0.5714	Remote Similarity	NPC611061
0.5686	Remote Similarity	NPC865
0.5625	Remote Similarity	NPC63061
0.5625	Remote Similarity	NPC475229
0.56	Remote Similarity	NPC326144
0.5593	Remote Similarity	NPC154971
0.5593	Remote Similarity	NPC121661
0.5577	Remote Similarity	NPC184928
0.5532	Remote Similarity	NPC474295
0.5517	Remote Similarity	NPC73467
0.5484	Remote Similarity	NPC126405
0.5484	Remote Similarity	NPC53669
0.5484	Remote Similarity	NPC77237
0.5484	Remote Similarity	NPC297271
0.5484	Remote Similarity	NPC224472
0.5484	Remote Similarity	NPC16791
0.5484	Remote Similarity	NPC217708
0.5424	Remote Similarity	NPC189239
0.5424	Remote Similarity	NPC252286
0.5417	Remote Similarity	NPC102256
0.5417	Remote Similarity	NPC475868
0.5349	Remote Similarity	NPC471182
0.5312	Remote Similarity	NPC280778
0.5246	Remote Similarity	NPC471154
0.5231	Remote Similarity	NPC83049
0.5231	Remote Similarity	NPC320471
0.5231	Remote Similarity	NPC118162
0.5185	Remote Similarity	NPC327651
0.5161	Remote Similarity	NPC198461
0.5091	Remote Similarity	NPC318286
0.5077	Remote Similarity	NPC475756
0.5075	Remote Similarity	NPC29727

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC256776 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5042
0.1-0.2	3972
0.2-0.3	130
0.3-0.4	6
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