NPASS Compound

Natural Product: NPC58223

Natural Product ID	NPC58223
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Isosilybin B
IUPAC Name	(2R,3R)-3,5,7-trihydroxy-2-[(2S,3S)-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3542340
PubChem CID	10885340
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001844] Flavonolignans

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 61 0 0 0 0 0 0 0 0999 V2000 -2.3505 2.6964 -1.8786 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8567 2.5116 -0.5953 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2826 1.2140 -0.0164 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8825 1.4082 -0.0113 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0288 0.6356 -0.7127 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3116 1.0788 -0.9783 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2072 0.2699 -1.6910 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7825 -0.9513 -2.1097 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4797 -1.3873 -1.8335 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3966 -0.6048 -1.1403 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7170 -0.9905 -0.8342 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7394 0.0232 -0.7872 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9341 -0.6411 -0.2561 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3023 -1.9200 -0.6890 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3977 -2.5836 -0.2380 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2035 -1.9708 0.7036 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8781 -0.7117 1.1577 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7496 -0.0530 0.6789 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7177 -0.1444 2.0993 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4129 1.1582 2.5928 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3178 -2.6772 1.1453 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5432 0.7931 -1.9352 C 0 0 1 0 0 0 0 0 0 0 0 0 4.0702 1.3541 -0.7164 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6748 0.5845 0.2583 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6890 0.9433 1.5936 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2925 0.1752 2.5664 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2932 0.5629 3.9207 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8954 -0.9885 2.1577 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8938 -1.3655 0.8354 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2852 -0.5860 -0.1286 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2556 -0.9385 -1.5346 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8639 -1.9611 -1.9206 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5278 -0.1359 -2.5626 C 0 0 2 0 0 0 0 0 0 0 0 0 5.5613 0.5979 -3.2073 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5006 -2.5456 0.3930 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3903 3.6347 -2.1743 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5060 3.3633 0.0223 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9624 2.5300 -0.5739 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5827 1.1237 1.0615 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6318 2.0612 -0.6335 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4531 -1.5846 -2.6543 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1728 -2.3457 -2.1720 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9097 0.2973 -1.8651 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6744 -2.4198 -1.4355 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6311 -3.5836 -0.6173 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5783 0.9277 1.0908 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4747 1.0797 3.1585 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2320 1.4799 3.2717 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3537 1.8776 1.7428 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2126 -2.5798 0.7018 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4431 1.6794 -2.6176 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2087 1.8586 1.8773 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8279 1.4129 4.1401 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3748 -1.6140 2.8778 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1605 -0.8088 -3.3257 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7123 1.3762 -2.6280 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5056 -2.6160 0.2773 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 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 17 19 1 0 19 20 1 0 16 21 1 0 7 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 26 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 31 33 1 0 33 34 1 0 29 35 1 0 12 3 1 0 18 13 1 0 33 22 1 0 10 5 1 0 30 24 1 0 1 36 1 0 2 37 1 0 2 38 1 0 3 39 1 1 6 40 1 0 8 41 1 0 9 42 1 0 12 43 1 6 14 44 1 0 15 45 1 0 18 46 1 0 20 47 1 0 20 48 1 0 20 49 1 0 21 50 1 0 22 51 1 6 25 52 1 0 27 53 1 0 28 54 1 0 33 55 1 6 34 56 1 0 35 57 1 0 M END

Standard InCHIKey	FDQAOULAVFHKBX-WAABAYLZSA-N
Standard InCHI	InChI=1S/C25H22O10/c1-32-17-6-11(2-4-14(17)28)24-20(10-26)33-18-7-12(3-5-16(18)34-24)25-23(31)22(30)21-15(29)8-13(27)9-19(21)35-25/h2-9,20,23-29,31H,10H2,1H3/t20-,23-,24-,25+/m0/s1
SMILES	OC[C@@H]1Oc2cc(ccc2O[C@H]1c1ccc(c(c1)OC)O)[C@H]1Oc2cc(O)cc(c2C(=O)[C@@H]1O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	482.12	Volume:	459.711 ? Van der Waals volume.
Dense:	1.049	LogP:	1.946 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.14 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.018 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	29.0
TPSA:	155.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	5.0	Rings:	5.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.374	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.992	Fsp³:	0.24
MCE-18:	97.742 ? 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:	Rejected	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.831	Fluc inhibitor:	0.487 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.059 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.547 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.368	Promiscuous compounds:	0.337

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.467	MDCK Permeability:	-5.267
Pgp-inhibitor:	0.998	Pgp-substrate:	0.157
PAMPA:	0.037 ? 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):	0.001
20% Bioavailability (F20%):	0.002	30% Bioavailability (F30%):	0.95
50% Bioavailability (F50%):	0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.885
Plasma Protein Binding (PPB):	95.289%	Volume Distribution (VD):	0.109
Fu:	4.076% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.994
BSEP inhibitor:	0.993

ADMET: Metabolism

CYP1A2-inhibitor:	0.928	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.004
CYP2C9-inhibitor:	0.042	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.066	CYP2D6-substrate:	0.932
CYP3A4-inhibitor:	0.357	CYP3A4-substrate:	0.67
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.945
HLM stability:	0.001 ? 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):

6.314

Half-life (T1/2):

2.036

ADMET: Toxicity

hERG Blockers:	0.11	hERG Blockers (10um):	0.354
Human Hepatotoxicity (H-HT):	0.935	Drug-induced Liver Injury (DILI):	0.878
AMES Toxicity:	0.771	Rat Oral Acute Toxicity:	0.562
Maximum Recommended Daily Dose:	0.272	Skin Sensitization:	0.997
Carcinogencity:	0.297	Eye Corrosion:	0.0
Eye Irritation:	0.865	Respiratory Toxicity:	0.544
Drug-induced Neurotoxicity:	0.454	Ototoxicity:	0.644
Hematotoxicity:	0.408	Drug-induced Nephrotoxicity:	0.908
Genotoxicity:	0.982	RPMI-8226 Immunitoxicity:	0.317
A549 Cytotoxicity:	0.91	Hek293 Cytotoxicity:	0.805
BCF:	0.921 ? 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:	3.536 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.897 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.098 ? 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
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1080/10496475.2013.791908]
NPO21361	Anastatica hierochuntica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12643908]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	whole plant	n.a.	PMID[16394559]
NPO21361	Anastatica hierochuntica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20189399]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24456525]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	Seeds	n.a.	n.a.	PMID[24597776]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21361	Anastatica hierochuntica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21361	Anastatica hierochuntica	Species	Brassicaceae	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	9
KA	1
KSV	1
Kis	2
Ki	4
IC50	4
Ratio	12

Activity Type	# Activity
Individual protein	15
Others	17
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	Inhibition	=	4.2	%	PMID[20189399]
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	Inhibition	=	4.8	%	PMID[20189399]
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	Inhibition	=	13.7	%	PMID[20189399]
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	Inhibition	=	30.8	%	PMID[20189399]
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	Inhibition	=	45.5	%	PMID[20189399]
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	KA	=	2.415	10'6L/mol	PMID[30871862]
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	KSV	=	0.0882	10'4L/mol	PMID[30871862]
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	Kis	=	25.2	uM	PMID[30871862]
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	Ki	=	12700.0	nM	PMID[30871862]
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	Ki	=	11600.0	nM	PMID[30871862]
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	IC50	=	19800.0	nM	PMID[30871862]
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	Ki	=	4300.0	nM	PMID[30871862]
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	Ki	=	4200.0	nM	PMID[30871862]
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	IC50	=	4900.0	nM	PMID[30871862]
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	Kis	=	8.0	uM	PMID[30871862]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	27000.0	nM	PMID[23673225]
NPT2	Others	Unspecified	n.a.	Inhibition	=	18.7	%	PMID[20189399]
NPT2	Others	Unspecified	n.a.	Inhibition	=	37.5	%	PMID[20189399]
NPT2	Others	Unspecified	n.a.	Inhibition	=	58.0	%	PMID[20189399]
NPT2	Others	Unspecified	n.a.	Inhibition	=	73.4	%	PMID[20189399]
NPT2	Others	Unspecified	n.a.	Ratio	=	0.79	n.a.	PMID[20189399]
NPT2	Others	Unspecified	n.a.	Ratio	=	1.15	n.a.	PMID[20189399]
NPT2	Others	Unspecified	n.a.	Ratio	=	1.33	n.a.	PMID[20189399]
NPT2	Others	Unspecified	n.a.	Ratio	=	0.87	n.a.	PMID[20189399]
NPT2	Others	Unspecified	n.a.	Ratio	=	1.22	n.a.	PMID[20189399]
NPT2	Others	Unspecified	n.a.	Ratio	=	1.02	n.a.	PMID[20189399]
NPT2	Others	Unspecified	n.a.	Ratio	=	1.14	n.a.	PMID[20189399]
NPT2	Others	Unspecified	n.a.	Ratio	=	0.97	n.a.	PMID[20189399]
NPT2	Others	Unspecified	n.a.	Ratio	=	0.7	n.a.	PMID[20189399]
NPT2	Others	Unspecified	n.a.	Ratio	=	0.74	n.a.	PMID[20189399]
NPT2	Others	Unspecified	n.a.	Ratio	=	0.64	n.a.	PMID[20189399]
NPT2	Others	Unspecified	n.a.	IC50	=	6100.0	nM	PMID[20189399]

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 NPC58223 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	24068
0.1-0.2	21513
0.2-0.3	3557
0.3-0.4	602
0.4-0.5	76
0.5-0.6	28
0.6-0.7	2
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	8

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC138688
1.0	High Similarity	NPC72787
1.0	High Similarity	NPC217795
0.9545	High Similarity	NPC36916
0.9545	High Similarity	NPC36
0.9545	High Similarity	NPC7154
0.9545	High Similarity	NPC125039
0.9545	High Similarity	NPC7688
0.7538	Intermediate Similarity	NPC326037
0.7538	Intermediate Similarity	NPC13858
0.6232	Remote Similarity	NPC320825
0.6076	Remote Similarity	NPC606364
0.5976	Remote Similarity	NPC279209
0.5976	Remote Similarity	NPC102277
0.5976	Remote Similarity	NPC479117
0.5942	Remote Similarity	NPC36835
0.5942	Remote Similarity	NPC246162
0.5942	Remote Similarity	NPC9743
0.5942	Remote Similarity	NPC260491
0.5942	Remote Similarity	NPC61506
0.5942	Remote Similarity	NPC240476
0.5811	Remote Similarity	NPC86030
0.5797	Remote Similarity	NPC44721
0.5797	Remote Similarity	NPC211466
0.5797	Remote Similarity	NPC605332
0.5775	Remote Similarity	NPC52530
0.5735	Remote Similarity	NPC62290
0.5735	Remote Similarity	NPC142731
0.5735	Remote Similarity	NPC326506
0.5647	Remote Similarity	NPC158188
0.5493	Remote Similarity	NPC250922
0.5467	Remote Similarity	NPC5851
0.5286	Remote Similarity	NPC4152
0.527	Remote Similarity	NPC236637
0.525	Remote Similarity	NPC126206
0.5211	Remote Similarity	NPC19721
0.5143	Remote Similarity	NPC21835
0.5135	Remote Similarity	NPC16435
0.507	Remote Similarity	NPC279417
0.507	Remote Similarity	NPC49130

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC58223 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5112
0.1-0.2	3941
0.2-0.3	88
0.3-0.4	5
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	3

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9545	High Similarity	NPD6166	Phase 2
0.9545	High Similarity	NPD6167	Clinical (unspecified phase)
0.9545	High Similarity	NPD6168	Clinical (unspecified phase)

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