NPASS Compound

Natural Product: NPC490701

Natural Product ID	NPC490701
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	4ÃÂ´-o-methyl-genistein
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0002586] O-methylated isoflavonoids [CHEMONTID:0002606] 4'-O-methylated isoflavonoids [CHEMONTID:0002687] 4'-O-methylisoflavones

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 33 35 0 0 0 0 0 0 0 0999 V2000 6.0680 0.7760 -0.5541 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2551 1.1210 0.5746 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8988 0.8304 0.5799 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2766 0.1973 -0.5010 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9261 -0.0629 -0.4324 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1501 0.2731 0.6593 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2617 -0.0331 0.6566 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8374 -0.5936 1.7805 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1179 -0.8785 1.7966 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8778 -0.6400 0.7534 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2254 -0.9378 0.7651 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0534 -0.7007 -0.3127 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4215 -1.0167 -0.2655 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5124 -0.1410 -1.4539 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1694 0.1662 -1.4925 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5814 0.7290 -2.6155 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3580 -0.0778 -0.4062 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0107 0.2404 -0.4708 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4990 0.7531 -1.5072 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7799 0.8951 1.7124 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1388 1.1730 1.6784 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0729 1.1944 -0.4704 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5397 1.1348 -1.4848 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1229 -0.3312 -0.5796 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8927 -0.0595 -1.3459 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4939 -0.5620 -1.3119 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1850 -0.7832 2.6368 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6929 -1.3835 1.6534 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7031 -1.9675 -0.0042 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1543 0.0569 -2.3259 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7538 1.6924 -2.8620 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2234 1.1817 2.5944 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5763 1.6720 2.5553 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 10 11 2 0 11 12 1 0 12 13 1 0 12 14 2 0 14 15 1 0 15 16 1 0 15 17 2 0 17 18 1 0 18 19 2 0 6 20 1 0 20 21 2 0 21 3 1 0 18 7 1 0 17 10 1 0 1 22 1 0 1 23 1 0 1 24 1 0 4 25 1 0 5 26 1 0 8 27 1 0 11 28 1 0 13 29 1 0 14 30 1 0 16 31 1 0 20 32 1 0 21 33 1 0 M END

Standard InCHIKey	WUADCCWRTIWANL-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H12O5/c1-20-11-4-2-9(3-5-11)12-8-21-14-7-10(17)6-13(18)15(14)16(12)19/h2-8,17-18H,1H3
SMILES	COC1=CC=C(C2=COC3=CC(O)=CC(O)=C3C2=O)C=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	284.07	Volume:	282.482 ? Van der Waals volume.
Dense:	1.006	LogP:	2.411 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.552 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.725 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
TPSA:	79.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.756	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.173	Fsp³:	0.062
MCE-18:	17.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.417	Fluc inhibitor:	0.996 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.864 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.658 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.59	Promiscuous compounds:	0.856

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.009	MDCK Permeability:	-4.829
Pgp-inhibitor:	0.154	Pgp-substrate:	0.321
PAMPA:	0.266 ? 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):	0.085
20% Bioavailability (F20%):	0.464	30% Bioavailability (F30%):	0.835
50% Bioavailability (F50%):	0.962

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.015	MRP1:	0.389
Plasma Protein Binding (PPB):	97.164%	Volume Distribution (VD):	-0.081
Fu:	2.088% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.758
OATP1B3 inhibitor:	0.932	BCRP inhibitor:	0.973
BSEP inhibitor:	0.712

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.947
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.295
CYP2C9-inhibitor:	0.987	CYP2C9-substrate:	0.998
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.99
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.965
CYP2B6-substrate:	0.013	CYP2C8-inhibitor:	1.0
HLM stability:	0.388 ? 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):

5.446

Half-life (T1/2):

0.858

ADMET: Toxicity

hERG Blockers:	0.188	hERG Blockers (10um):	0.545
Human Hepatotoxicity (H-HT):	0.465	Drug-induced Liver Injury (DILI):	0.898
AMES Toxicity:	0.661	Rat Oral Acute Toxicity:	0.526
Maximum Recommended Daily Dose:	0.78	Skin Sensitization:	0.336
Carcinogencity:	0.746	Eye Corrosion:	0.06
Eye Irritation:	0.985	Respiratory Toxicity:	0.844
Drug-induced Neurotoxicity:	0.304	Ototoxicity:	0.193
Hematotoxicity:	0.14	Drug-induced Nephrotoxicity:	0.246
Genotoxicity:	0.935	RPMI-8226 Immunitoxicity:	0.073
A549 Cytotoxicity:	0.237	Hek293 Cytotoxicity:	0.577
BCF:	1.269 ? 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:	4.01 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.787 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.38 ? 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
NPO41927	A new engineered strain of Bacillus subtilis [yyzE ypqE ptsG]	Strain	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	DOI[10.1002/biot.201700020]
NPO8210	Trigonella foenum-graecum	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11599360]
NPO8210	Trigonella foenum-graecum	Species	Fabaceae	Eukaryota	n.a.	seed	n.a.	PMID[21381697]
NPO18296	Diospyros kaki	Species	Ebenaceae	Eukaryota	n.a.	calyx	n.a.	PMID[21561086]
NPO18296	Diospyros kaki	Species	Ebenaceae	Eukaryota	n.a.	fruit	n.a.	PMID[24086493]
NPO19632	Terminalia ivorensis	Species	Combretaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36964494]
NPO8210	Trigonella foenum-graecum	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37120447]
NPO18296	Diospyros kaki	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37324556]
NPO12133	Corchorus olitorius	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38543013]
NPO47851	Escallonia pulverulenta	Species	Escalloniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39065498]
NPO53058	Eriosema montanum	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39769974]
NPO12133	Corchorus olitorius	Species	Malvaceae	Eukaryota	n.a.	leaf	n.a.	PMID[9658577]
NPO12133	Corchorus olitorius	Species	Malvaceae	Eukaryota	n.a.	leaf	n.a.	Database[Article]
NPO8210	Trigonella foenum-graecum	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12133	Corchorus olitorius	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18296	Diospyros kaki	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8210	Trigonella foenum-graecum	Species	Fabaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO12133	Corchorus olitorius	Species	Malvaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO12133	Corchorus olitorius	Species	Malvaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO8210	Trigonella foenum-graecum	Species	Fabaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO8210	Trigonella foenum-graecum	Species	Fabaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO12133	Corchorus olitorius	Species	Malvaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO8210	Trigonella foenum-graecum	Species	Fabaceae	Eukaryota	Plant	n.a.	n.a.	Database[FooDB]
NPO8210	Trigonella foenum-graecum	Species	Fabaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO8210	Trigonella foenum-graecum	Species	Fabaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO12133	Corchorus olitorius	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18296	Diospyros kaki	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8210	Trigonella foenum-graecum	Species	Fabaceae	Eukaryota	n.a.	n.a.		Database[Phenol-Explorer]
NPO12133	Corchorus olitorius	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8210	Trigonella foenum-graecum	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18296	Diospyros kaki	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18296	Diospyros kaki	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8210	Trigonella foenum-graecum	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO18296	Diospyros kaki	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO8210	Trigonella foenum-graecum	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18296	Diospyros kaki	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19632	Terminalia ivorensis	Species	Combretaceae	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
NPO12133	Corchorus olitorius	Dried	Stems	1.77	n.a.	n.a.	Âµg/100g	PMID[38543013]
NPO18296	Diospyros kaki	n.a.	n.a.	464.49 Â± 0.10	n.a.	n.a.	Î¼g/mL	PMID[37324556]
NPO19632	Terminalia ivorensis	Cold water extraction	n.a.	0.02	n.a.	n.a.	ng/mg	PMID[36964494]
NPO19632	Terminalia ivorensis	Cold water extraction	n.a.	18.9Â±4.7	n.a.	n.a.	%	PMID[36964494]
NPO19632	Terminalia ivorensis	Hot water extraction	n.a.	0.03	n.a.	n.a.	%	PMID[36964494]
NPO19632	Terminalia ivorensis	Hot water extraction	n.a.	16.3Â±4.0	n.a.	n.a.	ng/mg	PMID[36964494]
NPO19632	Terminalia ivorensis	Petroleum ether extract	n.a.	14.3Â±3.3	n.a.	n.a.	ng/mg	PMID[36964494]
NPO47851	Escallonia pulverulenta	n.a.	n.a.	13.74 Â± 1.49	n.a.	n.a.	mg/100g	PMID[39065498]
NPO47851	Escallonia pulverulenta	n.a.	n.a.	26.18 Â± 0.00	n.a.	n.a.	mg/100g	PMID[39065498]
NPO53058	Eriosema montanum	n.a.	n.a.	48.30352	n.a.	n.a.	mg/L	PMID[39769974]
NPO8210	Trigonella foenum-graecum	n.a.	n.a.	0.01	n.a.	n.a.	mg/100g	PMID[37120447]

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	22
IC50	12
Growth Rate	16
Activity	40
log(ratio)	1

Activity Type	# Activity
Individual protein	5
Cell line	74
Unchecked	4
Single protein	3
Protein family	5

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT261	Individual protein	Monoamine oxidase A	Homo sapiens	Inhibition	=	23.5	%	PMID[35101649]
NPT582	Individual protein	Monoamine oxidase B	Homo sapiens	Inhibition	=	36.8	%	PMID[35101649]
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	100.5	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT21762	Single protein	Lysine-specific histone demethylase 1	Homo sapiens	IC50	=	2950.0	nM	PMID[33581557]
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	101.28	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	63.14	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT21762	Single protein	Lysine-specific histone demethylase 1	Homo sapiens	IC50	=	2950.0	nM	PMID[35820351]
NPT21762	Single protein	Lysine-specific histone demethylase 1	Homo sapiens	IC50	=	2950.0	nM	PMID[35101649]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	40.0	ug.mL-1	PMID[33257172]
NPT1045	Cell line	U2OS	Homo sapiens	Growth Rate	=	0.77	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT2615	Cell line	HEK-293T	Homo sapiens	Growth Rate	=	1.0	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT2615	Cell line	HEK-293T	Homo sapiens	Growth Rate	=	0.75	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT81	Cell line	A549	Homo sapiens	Activity	=	92.0	%	PMID[36181478]
NPT1045	Cell line	U2OS	Homo sapiens	Growth Rate	=	0.95	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT3140	Cell line	MGC-803	Homo sapiens	IC50	=	6770.0	nM	PMID[33619958]
NPT34	Cell line	BV-2	Mus musculus	Inhibition	n.a.	n.a.	%	PMID[37137246]
NPT81	Cell line	A549	Homo sapiens	Inhibition	=	13.1	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	79.0	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Inhibition	=	16.2	%	PMID[36181478]
NPT1045	Cell line	U2OS	Homo sapiens	Growth Rate	=	0.85	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT81	Cell line	A549	Homo sapiens	Activity	=	1.973	um	PMID[36181478]
NPT3140	Cell line	MGC-803	Homo sapiens	IC50	=	6770.0	nM	PMID[33581557]
NPT81	Cell line	A549	Homo sapiens	Activity	=	1.854	um	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	1.568	um	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	1.552	um	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	0.405	um	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	171.0	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	20.0	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	n.a.	n.a.	n.a.	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Inhibition	=	50.0	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	19.0	%	PMID[36181478]
NPT1045	Cell line	U2OS	Homo sapiens	Growth Rate	=	0.93	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT81	Cell line	A549	Homo sapiens	Inhibition	n.a.	n.a.	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Inhibition	=	22.0	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Inhibition	=	63.29	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	0.481	um	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	61.3	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	0.302	um	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	52.0	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	76.0	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	44.1	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Inhibition	=	24.8	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	144.0	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	78.0	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	45.0	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	34.09	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	67.0	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	1.932	um	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	48.0	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	107.0	%	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	1.451	um	PMID[36181478]
NPT81	Cell line	A549	Homo sapiens	Activity	=	17.0	%	PMID[36181478]
NPT3140	Cell line	MGC-803	Homo sapiens	IC50	=	2950.0	nM	PMID[33619958]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	10000.0	nM	PMID[33257172]
NPT2615	Cell line	HEK-293T	Homo sapiens	Growth Rate	=	0.93	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT1045	Cell line	U2OS	Homo sapiens	Growth Rate	=	-0.91	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT1045	Cell line	U2OS	Homo sapiens	Growth Rate	=	1.0	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT28438	Unchecked	Unchecked	n.a.	Inhibition	n.a.	n.a.	%	PMID[36181478]
NPT28438	Unchecked	Unchecked	n.a.	log(ratio)	=	0.25	n.a.	PMID[35576701]
NPT25623	Protein family	Serine/threonine-protein kinase AKT	Homo sapiens	Inhibition	=	17.1	%	PMID[36181478]
NPT29337	Protein family	Cytochrome P450	Homo sapiens	Inhibition	<	15.0	%	PMID[35576701]
NPT25623	Protein family	Serine/threonine-protein kinase AKT	Homo sapiens	Inhibition	=	30.0	%	PMID[36181478]
NPT29337	Protein family	Cytochrome P450	Homo sapiens	Inhibition	=	25.0	%	PMID[35576701]
NPT25623	Protein family	Serine/threonine-protein kinase AKT	Homo sapiens	Inhibition	=	73.6	%	PMID[36181478]
NPT29444	Cell line	Fibroblast	Homo sapiens	Growth Rate	=	-0.08	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT29444	Cell line	Fibroblast	Homo sapiens	Growth Rate	=	0.69	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT29444	Cell line	Fibroblast	Homo sapiens	Growth Rate	=	0.21	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT29444	Cell line	Fibroblast	Homo sapiens	Growth Rate	=	0.94	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT29444	Cell line	Fibroblast	Homo sapiens	Growth Rate	=	0.87	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT29444	Cell line	Fibroblast	Homo sapiens	Growth Rate	=	0.58	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT29444	Cell line	Fibroblast	Homo sapiens	Growth Rate	=	-0.65	n.a.	EUbOPEN Chemogenomics Library - IncuCyte
NPT21769	Cell line	GES1	Homo sapiens	IC50	>	32000.0	nM	PMID[33619958]
NPT21769	Cell line	GES1	Homo sapiens	IC50	>	32000.0	nM	PMID[33581557]

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 NPC490701 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	26568
0.1-0.2	19657
0.2-0.3	2717
0.3-0.4	624
0.4-0.5	191
0.5-0.6	56
0.6-0.7	30
0.7-0.8	1
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC294409
0.8113	Intermediate Similarity	NPC200316
0.7963	Intermediate Similarity	NPC194653
0.7636	Intermediate Similarity	NPC279668
0.7636	Intermediate Similarity	NPC278323
0.7547	Intermediate Similarity	NPC78341
0.7255	Intermediate Similarity	NPC39426
0.7255	Intermediate Similarity	NPC608554
0.7222	Intermediate Similarity	NPC116632
0.7222	Intermediate Similarity	NPC35763
0.7193	Intermediate Similarity	NPC254702
0.7069	Intermediate Similarity	NPC104728
0.7049	Intermediate Similarity	NPC233918
0.7018	Intermediate Similarity	NPC481044
0.6964	Remote Similarity	NPC239363
0.6935	Remote Similarity	NPC479305
0.6897	Remote Similarity	NPC142876
0.6842	Remote Similarity	NPC309154
0.6786	Remote Similarity	NPC209560
0.6786	Remote Similarity	NPC490700
0.6731	Remote Similarity	NPC193792
0.6667	Remote Similarity	NPC19980
0.6667	Remote Similarity	NPC38065
0.661	Remote Similarity	NPC483637
0.661	Remote Similarity	NPC264550
0.6471	Remote Similarity	NPC156457
0.6462	Remote Similarity	NPC107838
0.6349	Remote Similarity	NPC133400
0.6333	Remote Similarity	NPC45291
0.6316	Remote Similarity	NPC10467
0.625	Remote Similarity	NPC268059
0.6207	Remote Similarity	NPC124714
0.6207	Remote Similarity	NPC303644
0.6207	Remote Similarity	NPC121522
0.6154	Remote Similarity	NPC128774
0.6129	Remote Similarity	NPC167595
0.6094	Remote Similarity	NPC249824
0.6094	Remote Similarity	NPC40942
0.6071	Remote Similarity	NPC87545
0.6061	Remote Similarity	NPC476178
0.6061	Remote Similarity	NPC474052
0.6034	Remote Similarity	NPC131266
0.6034	Remote Similarity	NPC269451
0.6034	Remote Similarity	NPC603503
0.597	Remote Similarity	NPC482075
0.5833	Remote Similarity	NPC209487
0.5781	Remote Similarity	NPC203636
0.5781	Remote Similarity	NPC608523
0.5763	Remote Similarity	NPC59951
0.5763	Remote Similarity	NPC231772
0.5763	Remote Similarity	NPC241838
0.5735	Remote Similarity	NPC231763
0.5735	Remote Similarity	NPC74178
0.5692	Remote Similarity	NPC213659
0.5692	Remote Similarity	NPC326109
0.5672	Remote Similarity	NPC280937
0.5667	Remote Similarity	NPC69430
0.5614	Remote Similarity	NPC182428
0.5614	Remote Similarity	NPC120924
0.5538	Remote Similarity	NPC238279
0.5522	Remote Similarity	NPC475705
0.5517	Remote Similarity	NPC223354
0.5507	Remote Similarity	NPC303197
0.5507	Remote Similarity	NPC600495
0.55	Remote Similarity	NPC7013
0.55	Remote Similarity	NPC333691
0.5484	Remote Similarity	NPC12377
0.5429	Remote Similarity	NPC52889
0.541	Remote Similarity	NPC181124
0.541	Remote Similarity	NPC245382
0.541	Remote Similarity	NPC216769
0.541	Remote Similarity	NPC610981
0.5405	Remote Similarity	NPC138540
0.5397	Remote Similarity	NPC80710
0.5397	Remote Similarity	NPC90665
0.5373	Remote Similarity	NPC606200
0.5362	Remote Similarity	NPC488570
0.5333	Remote Similarity	NPC481043
0.5333	Remote Similarity	NPC474264
0.5312	Remote Similarity	NPC55162
0.5312	Remote Similarity	NPC476055
0.5312	Remote Similarity	NPC114192
0.5246	Remote Similarity	NPC474340
0.5224	Remote Similarity	NPC85131
0.5224	Remote Similarity	NPC232947
0.5161	Remote Similarity	NPC186507
0.5161	Remote Similarity	NPC162680
0.5161	Remote Similarity	NPC136095
0.5161	Remote Similarity	NPC100971
0.5161	Remote Similarity	NPC609386
0.5156	Remote Similarity	NPC12175
0.5152	Remote Similarity	NPC93552
0.5143	Remote Similarity	NPC149875
0.5139	Remote Similarity	NPC474960
0.5125	Remote Similarity	NPC121647
0.5082	Remote Similarity	NPC605229
0.5079	Remote Similarity	NPC181209
0.5079	Remote Similarity	NPC250557
0.5079	Remote Similarity	NPC605826
0.5067	Remote Similarity	NPC73511

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC490701 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4559
0.1-0.2	4465
0.2-0.3	115
0.3-0.4	8
0.4-0.5	2
0.5-0.6	0
0.6-0.7	0
0.7-0.8	1
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
0.7255	Intermediate Similarity	NPD1510	Phase 2

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