NPASS Compound

Natural Product: NPC93739

Natural Product ID	NPC93739
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Physodic Acid
IUPAC Name	3,9-dihydroxy-6-oxo-7-(2-oxoheptyl)-1-pentylbenzo[b][1,4]benzodioxepine-2-carboxylic acid
Synonyms	NSC-685589
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL171637
PubChem CID	65751
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0001645] Depsides and depsidones

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 64 66 0 0 0 0 0 0 0 0999 V2000 9.5596 1.5094 0.4624 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1333 1.1777 0.8847 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8317 -0.2590 0.5568 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4471 -0.6239 0.9635 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4052 0.1976 0.2703 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0256 -0.1952 0.6631 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6546 0.1033 1.7842 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0807 -0.9443 -0.2699 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8936 -0.0648 -0.3439 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9099 1.2823 0.0232 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7955 2.0873 -0.0408 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4030 1.5887 -0.4778 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4762 0.2794 -0.8504 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6619 -0.5197 -0.7792 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7101 -1.9245 -1.1662 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8445 -2.3068 -1.4756 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3571 -2.8337 -1.2165 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7187 -2.6089 -0.9647 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4062 -3.7675 -0.6718 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7521 -3.6852 -0.4049 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4176 -2.4568 -0.4275 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6908 -1.3018 -0.7283 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3780 0.0087 -0.7468 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5761 0.5972 0.5997 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3165 1.9182 0.5264 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6917 1.7444 -0.0854 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3769 3.0887 -0.1107 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3369 -1.3722 -0.9984 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7688 -0.1089 -1.2802 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8381 -2.4356 -0.1577 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6320 -2.5439 -1.1438 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4235 -2.3102 1.0841 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5157 -4.8152 -0.1001 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8917 3.4111 0.3422 O 0 0 0 0 0 0 0 0 0 0 0 0 9.6083 1.5895 -0.6592 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8279 2.4952 0.8616 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2558 0.7356 0.8194 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4529 1.9005 0.3895 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0791 1.3663 1.9794 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8705 -0.3504 -0.5674 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6050 -0.8987 1.0249 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3610 -0.3978 2.0683 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2967 -1.7135 0.8432 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5577 1.2667 0.4898 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4827 0.0434 -0.8190 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6818 -1.0501 -1.1606 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9546 -1.8414 0.3809 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8649 1.7002 0.3703 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2917 2.2044 -0.5356 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9014 -4.7233 -0.6522 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7838 0.7076 -1.3576 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3877 -0.1854 -1.2080 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0633 -0.0194 1.3468 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5614 0.8670 1.0251 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4866 2.2577 1.5701 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7775 2.6769 -0.0592 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5950 1.4408 -1.1587 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3121 1.0394 0.4946 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1575 3.5648 0.8792 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0260 3.7690 -0.8913 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4945 2.9370 -0.1721 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2920 -1.8113 1.1877 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5838 -5.1239 0.8793 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0464 3.6373 1.3270 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 2 0 6 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 15 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 22 28 2 0 28 29 1 0 21 30 1 0 30 31 2 0 30 32 1 0 20 33 1 0 11 34 1 0 14 9 1 0 28 18 1 0 29 13 1 0 1 35 1 0 1 36 1 0 1 37 1 0 2 38 1 0 2 39 1 0 3 40 1 0 3 41 1 0 4 42 1 0 4 43 1 0 5 44 1 0 5 45 1 0 8 46 1 0 8 47 1 0 10 48 1 0 12 49 1 0 19 50 1 0 23 51 1 0 23 52 1 0 24 53 1 0 24 54 1 0 25 55 1 0 25 56 1 0 26 57 1 0 26 58 1 0 27 59 1 0 27 60 1 0 27 61 1 0 32 62 1 0 33 63 1 0 34 64 1 0 M END

Standard InCHIKey	KVTYWHGIZSCFLG-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C26H30O8/c1-3-5-7-9-16(27)11-15-12-17(28)13-20-22(15)26(32)34-21-14-19(29)23(25(30)31)18(24(21)33-20)10-8-6-4-2/h12-14,28-29H,3-11H2,1-2H3,(H,30,31)
SMILES	CCCCCC(=O)Cc1cc(cc2c1C(=O)Oc1cc(c(c(CCCCC)c1O2)C(=O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	470.19	Volume:	479.176 ? Van der Waals volume.
Dense:	0.981	LogP:	5.924 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.527 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.73 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	20.0
TPSA:	130.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.221	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.076	Fsp³:	0.423
MCE-18:	42.0 ? 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:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.552	Fluc inhibitor:	0.297 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.899 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.869 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.175	Promiscuous compounds:	0.247

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.987	MDCK Permeability:	-4.728
Pgp-inhibitor:	0.479	Pgp-substrate:	0.236
PAMPA:	0.422 ? 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):	0.067
20% Bioavailability (F20%):	0.09	30% Bioavailability (F30%):	0.599
50% Bioavailability (F50%):	0.682

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.95
Plasma Protein Binding (PPB):	98.431%	Volume Distribution (VD):	-0.186
Fu:	0.869% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.002
OATP1B3 inhibitor:	0.01	BCRP inhibitor:	0.32
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.951
CYP2C19-inhibitor:	0.003	CYP2C19-substrate:	0.995
CYP2C9-inhibitor:	0.935	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.999 ? 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):

0.674

Half-life (T1/2):

1.393

ADMET: Toxicity

hERG Blockers:	0.141	hERG Blockers (10um):	0.365
Human Hepatotoxicity (H-HT):	0.401	Drug-induced Liver Injury (DILI):	0.574
AMES Toxicity:	0.05	Rat Oral Acute Toxicity:	0.324
Maximum Recommended Daily Dose:	0.218	Skin Sensitization:	0.988
Carcinogencity:	0.059	Eye Corrosion:	0.424
Eye Irritation:	0.99	Respiratory Toxicity:	0.969
Drug-induced Neurotoxicity:	0.035	Ototoxicity:	0.313
Hematotoxicity:	0.252	Drug-induced Nephrotoxicity:	0.693
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.035
A549 Cytotoxicity:	0.267	Hek293 Cytotoxicity:	0.186
BCF:	1.262 ? 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:	4.178 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.461 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.552 ? 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
NPO40010	Alectoria sarmentosa	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7964789]
NPO8465	Maesa indica	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4891	Lentinellus ursinus	Species	Auriscalpiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7203	Lindera lucida	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5847	Moghania faginea	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4334	Garcinia griffithii	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4517	Laggera tomentosa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8465	Maesa indica	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4334	Garcinia griffithii	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4334	Garcinia griffithii	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8465	Maesa indica	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4517	Laggera tomentosa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4334	Garcinia griffithii	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9731	Roccella fuciformis	Species	Roccellaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5847	Moghania faginea	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO9715	Hypericum richeri	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24532	Ula pilosa	Species	Pediciidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8465	Maesa indica	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6552	Astrocasia phyllanthoides	Species	Phyllanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1286	Parmelia furfuracea	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9084	Rumex confertus	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4891	Lentinellus ursinus	Species	Auriscalpiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18984	Aster lautureanus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3334	Dicranum japonicum	Species	Dicranaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6307	Salix lasiolepis	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7203	Lindera lucida	Species	Lauraceae	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	8
IC50	12
Potency	26
EC50	10
AC50	2
Imax	6
Activity	2
ED50	1

Activity Type	# Activity
Individual protein	37
Cell line	1
Single protein	18
Organism	6
Non-molecular	5

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT12	Individual protein	Human immunodeficiency virus type 1 integrase	Human immunodeficiency virus 1	Inhibition	=	94.0	%	PMID[9083483]
NPT12	Individual protein	Human immunodeficiency virus type 1 integrase	Human immunodeficiency virus 1	Inhibition	=	79.5	%	PMID[9083483]
NPT12	Individual protein	Human immunodeficiency virus type 1 integrase	Human immunodeficiency virus 1	IC50	=	38500.0	nM	PMID[9083483]
NPT12	Individual protein	Human immunodeficiency virus type 1 integrase	Human immunodeficiency virus 1	IC50	=	30900.0	nM	PMID[9083483]
NPT12	Individual protein	Human immunodeficiency virus type 1 integrase	Human immunodeficiency virus 1	IC50	=	32500.0	nM	PMID[9083483]
NPT3	Individual protein	Thioredoxin glutathione reductase	Schistosoma mansoni	Potency	=	35481.3	nM	PubChem BioAssay data set
NPT1254	Individual protein	Streptokinase A	Streptococcus pyogenes serotype M1	EC50	=	6670.0	nM	PubChem BioAssay data set
NPT1254	Individual protein	Streptokinase A	Streptococcus pyogenes serotype M1	EC50	=	15899.0	nM	PubChem BioAssay data set
NPT1039	Individual protein	Envelope glycoprotein gp160	Human immunodeficiency virus 1	IC50	=	4100.0	nM	PubChem BioAssay data set
NPT198	Individual protein	Vitamin D receptor	Homo sapiens	Potency	n.a.	89125.1	nM	PubChem BioAssay data set
NPT2866	Individual protein	Replicative DNA helicase	Mycobacterium tuberculosis	AC50	=	2050.0	nM	PubChem BioAssay data set
NPT2867	Individual protein	Protein RecA	Mycobacterium tuberculosis	EC50	=	3230.0	nM	PubChem BioAssay data set
NPT199	Individual protein	DNA polymerase kappa	Homo sapiens	Potency	n.a.	79432.8	nM	PubChem BioAssay data set
NPT2866	Individual protein	Replicative DNA helicase	Mycobacterium tuberculosis	AC50	=	6087.0	nM	PubChem BioAssay data set
NPT154	Individual protein	Mothers against decapentaplegic homolog 3	Homo sapiens	Potency	n.a.	35481.3	nM	PubChem BioAssay data set
NPT10	Individual protein	Geminin	Homo sapiens	Potency	n.a.	1835.6	nM	PubChem BioAssay data set
NPT101	Individual protein	Glucagon-like peptide 1 receptor	Homo sapiens	Potency	n.a.	28183.8	nM	PubChem BioAssay data set
NPT161	Individual protein	Rap guanine nucleotide exchange factor 4	Homo sapiens	Potency	n.a.	15848.9	nM	PubChem BioAssay data set
NPT30	Individual protein	Cyclooxygenase-1	Homo sapiens	IC50	>	30000.0	nM	DOI[10.1039/C5MD00278H]
NPT55	Individual protein	Putative fructose-1,6-bisphosphate aldolase	Giardia intestinalis	Potency	=	25059.4	nM	PubChem BioAssay data set
NPT58	Individual protein	Bloom syndrome protein	Homo sapiens	Potency	=	3981.1	nM	PubChem BioAssay data set
NPT803	Individual protein	Flap endonuclease 1	Homo sapiens	Potency	n.a.	22387.2	nM	PubChem BioAssay data set
NPT9	Individual protein	DNA polymerase eta	Homo sapiens	Potency	n.a.	17782.8	nM	PubChem BioAssay data set
NPT26023	Single protein	Kinesin-like protein KIF20B	Homo sapiens	IC50	=	9900.0	nM	PMID[27300079]
NPT26023	Single protein	Kinesin-like protein KIF20B	Homo sapiens	Imax	=	85.0	%	PMID[27300079]
NPT26023	Single protein	Kinesin-like protein KIF20B	Homo sapiens	IC50	=	5800.0	nM	PMID[27300079]
NPT26023	Single protein	Kinesin-like protein KIF20B	Homo sapiens	Imax	=	90.0	%	PMID[27300079]
NPT26023	Single protein	Kinesin-like protein KIF20B	Homo sapiens	IC50	=	10400.0	nM	PMID[27300079]
NPT26023	Single protein	Kinesin-like protein KIF20B	Homo sapiens	IC50	=	4600.0	nM	PMID[27300079]
NPT26023	Single protein	Kinesin-like protein KIF20B	Homo sapiens	Imax	=	95.0	%	PMID[27300079]
NPT48	Individual protein	Lysine-specific demethylase 4D-like	Homo sapiens	Potency	=	39810.7	nM	PubChem BioAssay data set
NPT444	Individual protein	Ubiquitin carboxyl-terminal hydrolase 1	Homo sapiens	Potency	n.a.	50118.7	nM	PubChem BioAssay data set
NPT831	Individual protein	Serine/threonine-protein kinase PLK1	Homo sapiens	Potency	n.a.	23778.1	nM	PubChem BioAssay data set
NPT446	Individual protein	Rap guanine nucleotide exchange factor 3	Homo sapiens	Potency	n.a.	39810.7	nM	PubChem BioAssay data set
NPT27059	Single protein	Kinesin-like protein KIF9	Homo sapiens	Inhibition	=	40.0	%	PMID[27300079]
NPT27060	Single protein	Chromosome-associated kinesin KIF4A	Homo sapiens	Inhibition	=	40.0	%	PMID[27300079]
NPT27059	Single protein	Kinesin-like protein KIF9	Homo sapiens	Inhibition	=	50.0	%	PMID[27300079]
NPT51	Individual protein	Microtubule-associated protein tau	Homo sapiens	Potency	=	28183.8	nM	PubChem BioAssay data set
NPT60	Individual protein	Lysosomal alpha-glucosidase	Homo sapiens	Potency	=	44668.4	nM	PubChem BioAssay data set
NPT59	Individual protein	DNA polymerase beta	Homo sapiens	Potency	=	44668.4	nM	PubChem BioAssay data set
NPT63	Individual protein	Bromodomain adjacent to zinc finger domain protein 2B	Homo sapiens	Potency	n.a.	79432.8	nM	PubChem BioAssay data set
NPT8	Individual protein	DNA polymerase iota	Homo sapiens	Potency	n.a.	70794.6	nM	PubChem BioAssay data set
NPT478	Individual protein	Ataxin-2	Homo sapiens	Potency	n.a.	39810.7	nM	PubChem BioAssay data set
NPT821	Individual protein	Werner syndrome ATP-dependent helicase	Homo sapiens	Potency	n.a.	44668.4	nM	PubChem BioAssay data set
NPT27055	Single protein	Centromere-associated protein E	Homo sapiens	IC50	=	29600.0	nM	PMID[27300079]
NPT27055	Single protein	Centromere-associated protein E	Homo sapiens	Imax	=	70.0	%	PMID[27300079]
NPT27055	Single protein	Centromere-associated protein E	Homo sapiens	IC50	=	91400.0	nM	PMID[27300079]
NPT27055	Single protein	Centromere-associated protein E	Homo sapiens	Imax	=	60.0	%	PMID[27300079]
NPT47	Individual protein	ATP-dependent DNA helicase Q1	Homo sapiens	Potency	=	15848.9	nM	PubChem BioAssay data set
NPT532	Individual protein	Lysine-specific demethylase 4A	Homo sapiens	Potency	n.a.	79432.8	nM	PubChem BioAssay data set
NPT956	Individual protein	Prostaglandin E synthase	Homo sapiens	IC50	=	430.0	nM	DOI[10.1039/C5MD00278H]
NPT27052	Single protein	Kinesin-like protein KIF23	Homo sapiens	Inhibition	=	40.0	%	PMID[27300079]
NPT27058	Single protein	Kinesin-like protein KIF3B	Homo sapiens	Inhibition	=	40.0	%	PMID[27300079]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT65	Cell line	HepG2	Homo sapiens	Potency	n.a.	35481.3	nM	PubChem BioAssay data set
NPT174	Organism	Streptococcus	Streptococcus	EC50	>	150000.0	nM	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	9285.0	nM	PubChem BioAssay data set
NPT776	Organism	Spodoptera littoralis	Spodoptera littoralis	ED50	>	110.0	uM	DOI[10.1016/0305-1978(94)90001-9]
NPT602	Organism	Mycobacterium smegmatis	Mycobacterium smegmatis	Activity	=	100.0	ug ml-1	PMID[7964789]
NPT1252	Organism	Streptococcus sp. 'group A'	Streptococcus sp. 'group A'	EC50	=	2358.0	nM	PubChem BioAssay data set
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	EC50	>	50000.0	nM	PMID[27300079]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	EC50	=	38200.0	nM	PMID[27300079]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	EC50	=	31800.0	nM	PMID[27300079]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	EC50	=	32600.0	nM	PMID[27300079]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	EC50	=	37300.0	nM	PMID[27300079]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	Activity	=	25.0	ug ml-1	PMID[7964789]

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 NPC93739 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	13909
0.1-0.2	34608
0.2-0.3	1251
0.3-0.4	77
0.4-0.5	8
0.5-0.6	2
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8955	High Similarity	NPC284007
0.7973	Intermediate Similarity	NPC8070
0.7013	Intermediate Similarity	NPC267153
0.5783	Remote Similarity	NPC300984
0.5476	Remote Similarity	NPC6923

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC93739 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2915
0.1-0.2	6114
0.2-0.3	121
0.3-0.4	0
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