NPASS Compound

Natural Product: NPC167546

Natural Product ID	NPC167546
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	YJWBWQWUHVXPNC-CQSZACIVSA-N
IUPAC Name	n.a.
Synonyms	(-)-Dicentrine
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL478754
PubChem CID	317843
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0000381] Aporphines

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 46 50 0 0 0 0 0 0 0 0999 V2000 4.5451 1.8818 0.2695 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4447 0.5018 0.0626 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1940 -0.1075 0.0046 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0551 0.6956 0.1579 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8269 0.0845 0.0991 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7247 -1.2733 -0.1003 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8656 -2.0767 -0.2559 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0842 -1.4613 -0.1981 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2202 -2.2575 -0.3524 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1374 -3.6489 -0.5615 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6014 -1.9208 -0.0326 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6526 -1.0655 -0.5658 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6148 0.3197 -0.0823 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3780 0.9238 0.1223 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2709 2.2653 0.4668 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7349 3.1601 0.7327 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2264 4.4536 0.4888 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1119 4.2917 0.9487 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4435 2.9779 0.6029 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6765 2.3903 0.4070 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7757 1.0670 0.0654 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1027 0.4710 -0.1409 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8944 -0.7108 -1.0849 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9784 -1.6619 -0.5331 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.3436 -2.1816 0.7385 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1987 2.1203 1.2786 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9945 2.4550 -0.5016 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6399 2.1421 0.1848 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2182 1.7550 0.3104 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6935 -3.1181 -0.4094 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1517 -4.0041 -0.8374 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7690 -4.1817 0.3558 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3853 -3.8352 -1.3664 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4960 -2.8990 -0.5829 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7294 -2.1589 1.0767 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4535 -0.9749 -1.6922 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2421 4.6157 -0.6265 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7622 5.2274 1.0402 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6064 2.9554 0.5168 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8013 1.1614 -0.6811 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5324 0.1782 0.8135 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8465 -1.1369 -1.4287 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4042 -0.2734 -1.9919 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6940 -1.9106 1.5738 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3204 -3.3042 0.6647 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3859 -1.9321 1.0438 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 6 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 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 8 3 1 0 24 12 1 0 14 5 1 0 19 15 2 0 21 13 1 0 1 26 1 0 1 27 1 0 1 28 1 0 4 29 1 0 7 30 1 0 10 31 1 0 10 32 1 0 10 33 1 0 11 34 1 0 11 35 1 0 12 36 1 6 17 37 1 0 17 38 1 0 20 39 1 0 22 40 1 0 22 41 1 0 23 42 1 0 23 43 1 0 25 44 1 0 25 45 1 0 25 46 1 0 M END

Standard InCHIKey	YJWBWQWUHVXPNC-CQSZACIVSA-N
Standard InCHI	InChI=1S/C20H21NO4/c1-21-5-4-11-7-17-20(25-10-24-17)19-13-9-16(23-3)15(22-2)8-12(13)6-14(21)18(11)19/h7-9,14H,4-6,10H2,1-3H3/t14-/m1/s1
SMILES	COc1cc2c(cc1OC)C[C@@H]1c3c2c2OCOc2cc3CCN1C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	339.15	Volume:	342.033 ? Van der Waals volume.
Dense:	0.992	LogP:	2.572 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.71 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.894 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	24.0
TPSA:	40.16 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.84	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.117	Fsp³:	0.4
MCE-18:	87.286 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.604	Fluc inhibitor:	0.041 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.725 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.193 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.004	Promiscuous compounds:	0.895

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.713	MDCK Permeability:	-4.709
Pgp-inhibitor:	0.725	Pgp-substrate:	0.153
PAMPA:	0.008 ? 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):	0.002
20% Bioavailability (F20%):	0.152	30% Bioavailability (F30%):	0.018
50% Bioavailability (F50%):	0.882

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.879	MRP1:	0.804
Plasma Protein Binding (PPB):	72.243%	Volume Distribution (VD):	0.354
Fu:	26.999% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.988
OATP1B3 inhibitor:	0.992	BCRP inhibitor:	0.877
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.422	CYP2C9-substrate:	0.991
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.653
CYP3A4-inhibitor:	0.983	CYP3A4-substrate:	0.864
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	0.0
HLM stability:	0.466 ? 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):

7.863

Half-life (T1/2):

2.234

ADMET: Toxicity

hERG Blockers:	0.355	hERG Blockers (10um):	0.648
Human Hepatotoxicity (H-HT):	0.597	Drug-induced Liver Injury (DILI):	0.089
AMES Toxicity:	0.744	Rat Oral Acute Toxicity:	0.475
Maximum Recommended Daily Dose:	0.871	Skin Sensitization:	0.713
Carcinogencity:	0.826	Eye Corrosion:	0.001
Eye Irritation:	0.538	Respiratory Toxicity:	0.733
Drug-induced Neurotoxicity:	0.784	Ototoxicity:	0.449
Hematotoxicity:	0.262	Drug-induced Nephrotoxicity:	0.294
Genotoxicity:	0.484	RPMI-8226 Immunitoxicity:	0.072
A549 Cytotoxicity:	0.1	Hek293 Cytotoxicity:	0.397
BCF:	1.953 ? 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:	4.172 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.179 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.076 ? 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
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.3987/COM-96-7609.]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16038566]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	stem	n.a.	PMID[16964757]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18081254]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	root	n.a.	PMID[20030508]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[23059629]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[3728032]
NPO22151	Stephania pierrei	Species	Menispermaceae	Eukaryota	tubers	n.a.	n.a.	PMID[8254346]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Article]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2058	Sideritis discolor	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22151	Stephania pierrei	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4921	Brickellia diffusa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO628	Schisandra nigra	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3183	Phalaenopsis equestris	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14105.2	Panax pseudo-ginseng var. notoginseng	Varieties	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO628	Schisandra nigra	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14105.2	Panax pseudo-ginseng var. notoginseng	Varieties	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO8841	Shorea leprosula	Species	Dipterocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO413	Astragalus prusianus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2058	Sideritis discolor	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4921	Brickellia diffusa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22151	Stephania pierrei	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO628	Schisandra nigra	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2256	Pseudaxinyssa cantharella	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3183	Phalaenopsis equestris	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20755	Ballota hirsuta	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23324	Porphyridium purpureum	Species	Porphyridiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO189	Pachypodium lealii	Species	Apocynaceae	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
Potency	29
AC50	7
EC50	1
IC50	1
ED50	14
Ratio ED50	2
GI50	58

Activity Type	# Activity
Individual protein	27
Cell line	66
Organism	4
Non-molecular	5
Others	10

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1038	Individual protein	Histone-lysine N-methyltransferase MLL	Homo sapiens	Potency	=	31622.8	nM	PubChem BioAssay data set
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	Potency	n.a.	16360.1	nM	PubChem BioAssay data set
NPT2866	Individual protein	Replicative DNA helicase	Mycobacterium tuberculosis	AC50	=	26710.0	nM	PubChem BioAssay data set
NPT2867	Individual protein	Protein RecA	Mycobacterium tuberculosis	EC50	=	952.0	nM	PubChem BioAssay data set
NPT2866	Individual protein	Replicative DNA helicase	Mycobacterium tuberculosis	AC50	=	50810.0	nM	PubChem BioAssay data set
NPT10	Individual protein	Geminin	Homo sapiens	Potency	n.a.	29092.9	nM	PubChem BioAssay data set
NPT10	Individual protein	Geminin	Homo sapiens	Potency	n.a.	20596.2	nM	PubChem BioAssay data set
NPT1274	Individual protein	DNA repair protein RAD52 homolog	Homo sapiens	AC50	=	1180.0	nM	PubChem BioAssay data set
NPT105	Individual protein	Muscleblind-like protein 1	Homo sapiens	Potency	n.a.	79432.8	nM	PubChem BioAssay data set
NPT483	Individual protein	Prelamin-A/C	Homo sapiens	Potency	=	11220.2	nM	PubChem BioAssay data set
NPT531	Individual protein	Nuclear receptor ROR-gamma	Mus musculus	Potency	=	12589.3	nM	PubChem BioAssay data set
NPT55	Individual protein	Putative fructose-1,6-bisphosphate aldolase	Giardia intestinalis	Potency	=	500.0	nM	PubChem BioAssay data set
NPT531	Individual protein	Nuclear receptor ROR-gamma	Mus musculus	Potency	=	35481.3	nM	PubChem BioAssay data set
NPT803	Individual protein	Flap endonuclease 1	Homo sapiens	Potency	n.a.	2511.9	nM	PubChem BioAssay data set
NPT4907	Individual protein	Tyrosyl-DNA phosphodiesterase 2	Homo sapiens	IC50	=	7828.0	nM	PubChem BioAssay data set
NPT803	Individual protein	Flap endonuclease 1	Homo sapiens	Potency	n.a.	33807.8	nM	PubChem BioAssay data set
NPT48	Individual protein	Lysine-specific demethylase 4D-like	Homo sapiens	Potency	=	31622.8	nM	PubChem BioAssay data set
NPT444	Individual protein	Ubiquitin carboxyl-terminal hydrolase 1	Homo sapiens	Potency	n.a.	22387.2	nM	PubChem BioAssay data set
NPT51	Individual protein	Microtubule-associated protein tau	Homo sapiens	Potency	=	15848.9	nM	PubChem BioAssay data set
NPT59	Individual protein	DNA polymerase beta	Homo sapiens	Potency	=	56234.1	nM	PubChem BioAssay data set
NPT8	Individual protein	DNA polymerase iota	Homo sapiens	Potency	n.a.	2818.4	nM	PubChem BioAssay data set
NPT821	Individual protein	Werner syndrome ATP-dependent helicase	Homo sapiens	Potency	n.a.	56234.1	nM	PubChem BioAssay data set
NPT861	Individual protein	Isocitrate dehydrogenase [NADP] cytoplasmic	Homo sapiens	Potency	n.a.	32642.7	nM	PubChem BioAssay data set
NPT56	Individual protein	Beta-lactamase AmpC	Escherichia coli K-12	Potency	=	4466.8	nM	PubChem BioAssay data set
NPT532	Individual protein	Lysine-specific demethylase 4A	Homo sapiens	Potency	n.a.	50118.7	nM	PubChem BioAssay data set
NPT84	Individual protein	Dual specificity tyrosine-phosphorylation-regulated kinase 1A	Rattus norvegicus	AC50	=	2087.0	nM	PubChem BioAssay data set
NPT867	Individual protein	Caspase-6	Homo sapiens	AC50	=	5630.0	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT453	Cell line	HT-1080	Homo sapiens	ED50	=	1.7	ug ml-1	PMID[8254346]
NPT147	Cell line	SK-MEL-2	Homo sapiens	ED50	=	3.8	ug ml-1	PMID[8254346]
NPT91	Cell line	KB	Homo sapiens	ED50	=	1.6	ug ml-1	PMID[8254346]
NPT168	Cell line	P388	Mus musculus	ED50	=	0.6	ug ml-1	PMID[8254346]
NPT762	Cell line	A-431	Homo sapiens	ED50	=	1.7	ug ml-1	PMID[8254346]
NPT858	Cell line	LNCaP	Homo sapiens	ED50	=	1.9	ug ml-1	PMID[8254346]
NPT133	Cell line	ZR-75-1	Homo sapiens	ED50	=	2.8	ug ml-1	PMID[8254346]
NPT71	Cell line	HEK293	Homo sapiens	Potency	n.a.	1458.1	nM	PubChem BioAssay data set
NPT368	Cell line	SN12C	Homo sapiens	GI50	n.a.	6137.62	nM	PubChem BioAssay data set
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	n.a.	10232.93	nM	PubChem BioAssay data set
NPT371	Cell line	UO-31	Homo sapiens	GI50	n.a.	11830.42	nM	PubChem BioAssay data set
NPT116	Cell line	HL-60	Homo sapiens	GI50	n.a.	7261.06	nM	PubChem BioAssay data set
NPT372	Cell line	HOP-92	Homo sapiens	GI50	n.a.	6776.42	nM	PubChem BioAssay data set
NPT374	Cell line	SF-539	Homo sapiens	GI50	n.a.	5942.92	nM	PubChem BioAssay data set
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	n.a.	7516.23	nM	PubChem BioAssay data set
NPT375	Cell line	Malme-3M	Homo sapiens	GI50	n.a.	9141.13	nM	PubChem BioAssay data set
NPT376	Cell line	A498	Homo sapiens	GI50	n.a.	4688.13	nM	PubChem BioAssay data set
NPT111	Cell line	K562	Homo sapiens	GI50	n.a.	5357.97	nM	PubChem BioAssay data set
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	n.a.	3845.92	nM	PubChem BioAssay data set
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	n.a.	13551.89	nM	PubChem BioAssay data set
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	GI50	n.a.	5623.41	nM	PubChem BioAssay data set
NPT379	Cell line	HOP-62	Homo sapiens	GI50	n.a.	3572.73	nM	PubChem BioAssay data set
NPT380	Cell line	U-251	Homo sapiens	GI50	n.a.	10789.47	nM	PubChem BioAssay data set
NPT381	Cell line	OVCAR-8	Homo sapiens	GI50	n.a.	4591.98	nM	PubChem BioAssay data set
NPT382	Cell line	OVCAR-5	Homo sapiens	GI50	n.a.	9638.29	nM	PubChem BioAssay data set
NPT383	Cell line	SNB-19	Homo sapiens	GI50	n.a.	5741.16	nM	PubChem BioAssay data set
NPT572	Cell line	DMS-273	Homo sapiens	GI50	n.a.	3515.6	nM	PubChem BioAssay data set
NPT573	Cell line	M19-MEL	Homo sapiens	GI50	n.a.	10447.2	nM	PubChem BioAssay data set
NPT323	Cell line	SW-620	Homo sapiens	GI50	n.a.	3917.42	nM	PubChem BioAssay data set
NPT455	Cell line	NCI-H522	Homo sapiens	GI50	n.a.	6698.85	nM	PubChem BioAssay data set
NPT386	Cell line	KM12	Homo sapiens	GI50	n.a.	7396.05	nM	PubChem BioAssay data set
NPT574	Cell line	XF498	Homo sapiens	GI50	n.a.	13899.53	nM	PubChem BioAssay data set
NPT388	Cell line	NCI-H322M	Homo sapiens	GI50	n.a.	2904.02	nM	PubChem BioAssay data set
NPT389	Cell line	RPMI-8226	Homo sapiens	GI50	n.a.	5741.16	nM	PubChem BioAssay data set
NPT456	Cell line	OVCAR-4	Homo sapiens	GI50	n.a.	8260.38	nM	PubChem BioAssay data set
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	n.a.	3784.43	nM	PubChem BioAssay data set
NPT168	Cell line	P388	Mus musculus	GI50	n.a.	8531.0	nM	PubChem BioAssay data set
NPT147	Cell line	SK-MEL-2	Homo sapiens	GI50	n.a.	10914.4	nM	PubChem BioAssay data set
NPT575	Cell line	KM-20L2	Homo sapiens	GI50	n.a.	3443.5	nM	PubChem BioAssay data set
NPT391	Cell line	HCC 2998	Homo sapiens	GI50	n.a.	9354.06	nM	PubChem BioAssay data set
NPT81	Cell line	A549	Homo sapiens	GI50	n.a.	3341.95	nM	PubChem BioAssay data set
NPT392	Cell line	SNB-75	Homo sapiens	GI50	n.a.	7294.58	nM	PubChem BioAssay data set
NPT393	Cell line	HCT-116	Homo sapiens	GI50	n.a.	2870.78	nM	PubChem BioAssay data set
NPT148	Cell line	HCT-15	Homo sapiens	GI50	n.a.	5767.66	nM	PubChem BioAssay data set
NPT395	Cell line	SF-268	Homo sapiens	GI50	n.a.	7691.3	nM	PubChem BioAssay data set
NPT394	Cell line	EKVX	Homo sapiens	GI50	n.a.	11376.27	nM	PubChem BioAssay data set
NPT83	Cell line	MCF7	Homo sapiens	GI50	n.a.	1940.89	nM	PubChem BioAssay data set
NPT576	Cell line	DMS-114	Homo sapiens	GI50	n.a.	8433.35	nM	PubChem BioAssay data set
NPT146	Cell line	SK-OV-3	Homo sapiens	GI50	n.a.	12133.89	nM	PubChem BioAssay data set
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	n.a.	2529.3	nM	PubChem BioAssay data set
NPT398	Cell line	UACC-62	Homo sapiens	GI50	n.a.	8375.29	nM	PubChem BioAssay data set
NPT552	Cell line	P388/ADR	Mus musculus	GI50	n.a.	7079.46	nM	PubChem BioAssay data set
NPT308	Cell line	CAKI-1	Homo sapiens	GI50	n.a.	6011.74	nM	PubChem BioAssay data set
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	n.a.	9616.12	nM	PubChem BioAssay data set
NPT399	Cell line	SF-295	Homo sapiens	GI50	n.a.	1636.82	nM	PubChem BioAssay data set
NPT578	Cell line	SNB-78	Homo sapiens	GI50	n.a.	11561.12	nM	PubChem BioAssay data set
NPT403	Cell line	UACC-257	Homo sapiens	GI50	n.a.	11614.49	nM	PubChem BioAssay data set
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	n.a.	3962.78	nM	PubChem BioAssay data set
NPT579	Cell line	DLD-1	Homo sapiens	GI50	n.a.	5997.91	nM	PubChem BioAssay data set
NPT139	Cell line	HT-29	Homo sapiens	GI50	n.a.	6397.35	nM	PubChem BioAssay data set
NPT405	Cell line	NCI-H226	Homo sapiens	GI50	n.a.	7063.18	nM	PubChem BioAssay data set
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	n.a.	12161.86	nM	PubChem BioAssay data set
NPT407	Cell line	COLO 205	Homo sapiens	GI50	n.a.	4226.69	nM	PubChem BioAssay data set
NPT406	Cell line	RXF 393	Homo sapiens	GI50	n.a.	8035.26	nM	PubChem BioAssay data set
NPT732	Cell line	HOP-18	Homo sapiens	GI50	n.a.	18155.16	nM	PubChem BioAssay data set
NPT738	Cell line	SN12K1	Homo sapiens	GI50	n.a.	6095.37	nM	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	ED50	=	1260.0	ng/ml	PMID[8254346]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	ED50	=	2550.0	ng/ml	PMID[8254346]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	928.5	nM	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	18526.0	nM	PubChem BioAssay data set
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	2.2	ug ml-1	PMID[8254346]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	6.1	ug ml-1	PMID[8254346]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	2.1	ug ml-1	PMID[8254346]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.9	ug ml-1	PMID[8254346]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	1.5	ug ml-1	PMID[8254346]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	4.0	n.a.	PMID[8254346]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	2.0	n.a.	PMID[8254346]
NPT2	Others	Unspecified	n.a.	Potency	=	16360.1	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	10000.0	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	AC50	n.a.	17620.0	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	AC50	n.a.	116160.0	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	22387.2	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	29092.9	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	2511.9	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	14125.4	nM	PubChem BioAssay data set

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 NPC167546 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	37727
0.1-0.2	11069
0.2-0.3	812
0.3-0.4	184
0.4-0.5	28
0.5-0.6	10
0.6-0.7	14
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC63997
1.0	High Similarity	NPC16805
0.8182	Intermediate Similarity	NPC99659
0.8182	Intermediate Similarity	NPC325871
0.7705	Intermediate Similarity	NPC266753
0.7705	Intermediate Similarity	NPC160298
0.7619	Intermediate Similarity	NPC229166
0.7419	Intermediate Similarity	NPC19520
0.7344	Intermediate Similarity	NPC128560
0.7097	Intermediate Similarity	NPC306902
0.7097	Intermediate Similarity	NPC232924
0.7097	Intermediate Similarity	NPC247389
0.6875	Remote Similarity	NPC219341
0.6875	Remote Similarity	NPC476432
0.6875	Remote Similarity	NPC24264
0.6667	Remote Similarity	NPC298979
0.6667	Remote Similarity	NPC320223
0.6667	Remote Similarity	NPC600118
0.6667	Remote Similarity	NPC610764
0.6615	Remote Similarity	NPC226102
0.6515	Remote Similarity	NPC199465
0.6471	Remote Similarity	NPC114364
0.6406	Remote Similarity	NPC253043
0.6364	Remote Similarity	NPC605845
0.6154	Remote Similarity	NPC239775
0.6154	Remote Similarity	NPC136508
0.5938	Remote Similarity	NPC326316
0.5938	Remote Similarity	NPC81733
0.5658	Remote Similarity	NPC606311
0.5493	Remote Similarity	NPC248642
0.5417	Remote Similarity	NPC602113
0.5211	Remote Similarity	NPC126284
0.5211	Remote Similarity	NPC261206
0.5143	Remote Similarity	NPC205421
0.5143	Remote Similarity	NPC474931
0.5143	Remote Similarity	NPC607722

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC167546 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6219
0.1-0.2	2830
0.2-0.3	89
0.3-0.4	11
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