NPASS Compound

Natural Product: NPC7846

Natural Product ID	NPC7846
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Sid489025
IUPAC Name	2-(3,4-dimethoxyphenyl)-5-hydroxy-3,6,7,8-tetramethoxychromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL422237
PubChem CID	136417
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0002585] O-methylated flavonoids [CHEMONTID:0002593] 8-O-methylated flavonoids

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 52 54 0 0 0 0 0 0 0 0999 V2000 5.4952 1.2814 -4.5686 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6903 0.2232 -4.0850 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7387 0.4066 -3.1032 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5335 1.6496 -2.5475 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5610 1.7980 -1.5551 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7817 0.7847 -1.0815 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0213 -0.4657 -1.6741 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9710 -0.6438 -2.6536 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1975 -1.8914 -3.2325 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4149 -2.9897 -2.7817 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7920 0.8473 -0.0311 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6797 1.8998 0.8118 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2931 1.9453 1.8287 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3795 2.9173 2.5859 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1329 0.8640 1.9347 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1268 0.8068 2.9038 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9395 -0.2996 2.9664 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8067 -1.3634 2.0992 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8211 -1.3004 1.1426 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9742 -0.1843 1.0517 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0590 -0.1892 0.1193 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6433 -2.3349 0.2497 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2963 -2.4109 -1.0009 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6659 -2.4532 2.2206 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8987 -2.5281 1.5334 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9342 -0.3607 3.9336 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2448 0.1452 3.6554 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2533 1.8860 3.7752 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4889 2.9890 0.7606 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6829 3.1334 1.5214 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2546 0.8957 -5.2724 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8904 2.0983 -5.0030 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0754 1.6485 -3.6800 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1227 2.4771 -2.8864 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4388 2.7962 -1.2005 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4215 -1.2868 -1.3217 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8589 -3.9601 -3.1302 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4031 -3.0430 -1.6579 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4129 -2.9323 -3.2164 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7028 -1.9444 -1.8056 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2773 -1.8934 -0.9918 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5023 -3.4815 -1.2079 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7482 -2.6815 2.2499 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8243 -3.3554 0.8079 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1103 -1.5459 1.0453 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2637 0.6246 2.6570 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9798 -0.7099 3.6683 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5580 0.8905 4.4107 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5059 1.7893 4.7429 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5190 3.6942 2.4520 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4235 3.6512 0.8770 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0726 2.1064 1.6835 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 2 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 19 22 1 0 22 23 1 0 18 24 1 0 24 25 1 0 17 26 1 0 26 27 1 0 16 28 1 0 12 29 1 0 29 30 1 0 8 3 1 0 21 11 1 0 20 15 1 0 1 31 1 0 1 32 1 0 1 33 1 0 4 34 1 0 5 35 1 0 7 36 1 0 10 37 1 0 10 38 1 0 10 39 1 0 23 40 1 0 23 41 1 0 23 42 1 0 25 43 1 0 25 44 1 0 25 45 1 0 27 46 1 0 27 47 1 0 27 48 1 0 28 49 1 0 30 50 1 0 30 51 1 0 30 52 1 0 M END

Standard InCHIKey	JDVPHCLYMGBZLE-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C21H22O9/c1-24-11-8-7-10(9-12(11)25-2)16-18(26-3)14(22)13-15(23)19(27-4)21(29-6)20(28-5)17(13)30-16/h7-9,23H,1-6H3
SMILES	COc1ccc(cc1OC)c1c(c(=O)c2c(c(c(c(c2o1)OC)OC)OC)O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	418.13	Volume:	404.123 ? Van der Waals volume.
Dense:	1.035	LogP:	2.058 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.371 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.313 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	18.0
TPSA:	105.82 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.619	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.551	Fsp³:	0.286
MCE-18:	21.0 ? 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:	0.07	Fluc inhibitor:	0.503 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.779 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.688 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.314	Promiscuous compounds:	0.367

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.915	MDCK Permeability:	-4.658
Pgp-inhibitor:	0.969	Pgp-substrate:	0.136
PAMPA:	0.028 ? 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):	0.035
20% Bioavailability (F20%):	0.022	30% Bioavailability (F30%):	0.032
50% Bioavailability (F50%):	0.939

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.09	MRP1:	0.984
Plasma Protein Binding (PPB):	96.27%	Volume Distribution (VD):	-0.341
Fu:	3.112% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.109
OATP1B3 inhibitor:	0.954	BCRP inhibitor:	0.961
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.991	CYP1A2-substrate:	0.019
CYP2C19-inhibitor:	0.6	CYP2C19-substrate:	0.482
CYP2C9-inhibitor:	0.119	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.815	CYP2D6-substrate:	0.833
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.852
CYP2B6-substrate:	0.011	CYP2C8-inhibitor:	0.954
HLM stability:	0.721 ? 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):

5.606

Half-life (T1/2):

1.734

ADMET: Toxicity

hERG Blockers:	0.098	hERG Blockers (10um):	0.512
Human Hepatotoxicity (H-HT):	0.434	Drug-induced Liver Injury (DILI):	0.712
AMES Toxicity:	0.316	Rat Oral Acute Toxicity:	0.357
Maximum Recommended Daily Dose:	0.28	Skin Sensitization:	0.584
Carcinogencity:	0.795	Eye Corrosion:	0.308
Eye Irritation:	0.83	Respiratory Toxicity:	0.678
Drug-induced Neurotoxicity:	0.518	Ototoxicity:	0.223
Hematotoxicity:	0.52	Drug-induced Nephrotoxicity:	0.276
Genotoxicity:	0.1	RPMI-8226 Immunitoxicity:	0.154
A549 Cytotoxicity:	0.147	Hek293 Cytotoxicity:	0.325
BCF:	1.5 ? 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:	3.561 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.781 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.967 ? 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
NPO32678	acronychia porteri	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7964782]
NPO33371	zieridium pseudobtusifolium	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[7964782]

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
IC50	8
Inhibition	1
Potency	21
EC50	3
GI50	61
AC50	1

Activity Type	# Activity
Individual protein	16
Cell line	66
Protein complex	2
Organism	2
Others	9

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	Potency	n.a.	14581.0	nM	PMID[18603337]
NPT135	Individual protein	Chromobox protein homolog 1	Homo sapiens	Potency	n.a.	17782.8	nM	PMID[8627602]
NPT1323	Individual protein	Botulinum neurotoxin type A	Clostridium botulinum (strain Hall / ATCC 3502 / NCTC 13319 / Type A)	EC50	n.a.	20000.0	nM	PMID[22233864]
NPT150	Individual protein	Anthrax lethal factor	Bacillus anthracis	EC50	n.a.	20000.0	nM	PMID[23822611]
NPT10	Individual protein	Geminin	Homo sapiens	Potency	n.a.	23109.3	nM	PMID[25760525]
NPT101	Individual protein	Glucagon-like peptide 1 receptor	Homo sapiens	Potency	n.a.	2818.4	nM	PMID[20970332]
NPT160	Individual protein	TAR DNA-binding protein 43	Homo sapiens	Potency	n.a.	35481.3	nM	PMID[15781124]
NPT105	Individual protein	Muscleblind-like protein 1	Homo sapiens	Potency	n.a.	19952.6	nM	PMID[18625769]
NPT531	Individual protein	Nuclear receptor ROR-gamma	Mus musculus	Potency	=	25118.9	nM	PMID[22037378]
NPT531	Individual protein	Nuclear receptor ROR-gamma	Mus musculus	Potency	=	11220.2	nM	PMID[19451298]
NPT48	Individual protein	Lysine-specific demethylase 4D-like	Homo sapiens	Potency	=	35481.3	nM	PMID[25019388]
NPT518	Protein complex	Tubulin	Homo sapiens	IC50	>	40000.0	nM	PMID[21513293]
NPT518	Protein complex	Tubulin	Homo sapiens	Inhibition	=	4.0	%	DOI[10.1007/s00044-011-9693-2]
NPT51	Individual protein	Microtubule-associated protein tau	Homo sapiens	Potency	=	28183.8	nM	Open TG-GATES in vivo data: Hematology
NPT60	Individual protein	Lysosomal alpha-glucosidase	Homo sapiens	Potency	=	39810.7	nM	DOI[10.6019/CHEMBL1201861]
NPT755	Individual protein	Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1	Homo sapiens	Potency	n.a.	79432.8	nM	PMID[22194678]
NPT6277	Individual protein	Botulinum neurotoxin type F	Clostridium botulinum	EC50	n.a.	20000.0	nM	DOI[10.6019/CHEMBL1201861]
NPT64	Individual protein	ATPase family AAA domain-containing protein 5	Homo sapiens	Potency	n.a.	11577.4	nM	PMID[19845338]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT517	Cell line	Panel NCI-60 (60 carcinoma cell lines)	Homo sapiens	GI50	=	7100.0	nM	DOI[10.1007/s00044-012-0292-7]
NPT116	Cell line	HL-60	Homo sapiens	IC50	=	4160.0	nM	PMID[16033274]
NPT116	Cell line	HL-60	Homo sapiens	AC50	=	5900.0	nM	PMID[1336040]
NPT91	Cell line	KB	Homo sapiens	IC50	=	6.0	ug.mL-1	PMID[18808182]
NPT65	Cell line	HepG2	Homo sapiens	Potency	n.a.	22387.2	nM	PMID[15943472]
NPT368	Cell line	SN12C	Homo sapiens	GI50	n.a.	26242.19	nM	PMID[16472241]
NPT367	Cell line	MDA-N	Homo sapiens	GI50	n.a.	10280.16	nM	PMID[19651905]
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	n.a.	31117.16	nM	PMID[22584254]
NPT371	Cell line	UO-31	Homo sapiens	GI50	n.a.	9057.33	nM	PMID[25744190]
NPT369	Cell line	ACHN	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT116	Cell line	HL-60	Homo sapiens	GI50	n.a.	6807.69	nM	PMID[19506060]
NPT372	Cell line	HOP-92	Homo sapiens	GI50	n.a.	243.22	nM	PMID[20151678]
NPT374	Cell line	SF-539	Homo sapiens	GI50	n.a.	19408.86	nM	PMID[218014]
NPT90	Cell line	DU-145	Homo sapiens	GI50	n.a.	36224.3	nM	PMID[15050646]
NPT375	Cell line	Malme-3M	Homo sapiens	GI50	n.a.	46773.51	nM	PMID[24411478]
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	n.a.	9705.1	nM	DOI[10.6019/CHEMBL1201861]
NPT111	Cell line	K562	Homo sapiens	GI50	n.a.	10592.54	nM	Open TG-GATES in vivo data: Hematology
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	n.a.	22698.65	nM	DOI[10.1039/C4MD00325J]
NPT376	Cell line	A498	Homo sapiens	GI50	n.a.	19860.95	nM	PMID[25499431]
NPT379	Cell line	HOP-62	Homo sapiens	GI50	n.a.	19453.6	nM	DrugMatrix in vitro pharmacology data
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	n.a.	15452.54	nM	PMID[25581396]
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	GI50	n.a.	13273.94	nM	PMID[10514320]
NPT380	Cell line	U-251	Homo sapiens	GI50	n.a.	27733.2	nM	PMID[19332671]
NPT381	Cell line	OVCAR-8	Homo sapiens	GI50	n.a.	25409.73	nM	PMID[21683602]
NPT382	Cell line	OVCAR-5	Homo sapiens	GI50	n.a.	35563.13	nM	PMID[7807120]
NPT383	Cell line	SNB-19	Homo sapiens	GI50	n.a.	63386.97	nM	PMID[25052206]
NPT82	Cell line	MDA-MB-231	Homo sapiens	GI50	n.a.	22233.1	nM	PMID[17228858]
NPT385	Cell line	SR	Homo sapiens	GI50	n.a.	7870.46	nM	DOI[10.6019/CHEMBL1201861]
NPT323	Cell line	SW-620	Homo sapiens	GI50	n.a.	20796.97	nM	PMID[19700322]
NPT384	Cell line	TK-10	Homo sapiens	GI50	n.a.	36224.3	nM	PubChem BioAssay data set
NPT455	Cell line	NCI-H522	Homo sapiens	GI50	n.a.	14288.94	nM	PMID[3735324]
NPT387	Cell line	M14	Homo sapiens	GI50	n.a.	26424.09	nM	PMID[21489793]
NPT386	Cell line	KM12	Homo sapiens	GI50	n.a.	24434.31	nM	PMID[18656367]
NPT388	Cell line	NCI-H322M	Homo sapiens	GI50	n.a.	46238.1	nM	PMID[18936192]
NPT389	Cell line	RPMI-8226	Homo sapiens	GI50	n.a.	16710.91	nM	DrugMatrix in vivo data: Hematology
NPT456	Cell line	OVCAR-4	Homo sapiens	GI50	n.a.	26485.0	nM	PMID[10924160]
NPT457	Cell line	BT-549	Homo sapiens	GI50	n.a.	34434.99	nM	PMID[19223646]
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	n.a.	11015.39	nM	PMID[25981688]
NPT147	Cell line	SK-MEL-2	Homo sapiens	GI50	n.a.	15100.8	nM	PMID[8021914]
NPT1635	Cell line	H9c2	Rattus norvegicus	IC50	>	79000.0	nM	DrugMatrix in vitro pharmacology data
NPT81	Cell line	A549	Homo sapiens	GI50	n.a.	27478.94	nM	PMID[20970332]
NPT391	Cell line	HCC 2998	Homo sapiens	GI50	n.a.	19319.68	nM	PMID[16933872]
NPT392	Cell line	SNB-75	Homo sapiens	GI50	n.a.	1663.41	nM	PMID[25211145]
NPT148	Cell line	HCT-15	Homo sapiens	GI50	n.a.	13963.68	nM	PMID[23398362]
NPT395	Cell line	SF-268	Homo sapiens	GI50	n.a.	9332.54	nM	PMID[16872140]
NPT393	Cell line	HCT-116	Homo sapiens	GI50	n.a.	24945.95	nM	PMID[11520240]
NPT83	Cell line	MCF7	Homo sapiens	GI50	n.a.	3971.92	nM	PMID[22506638]
NPT394	Cell line	EKVX	Homo sapiens	GI50	n.a.	37583.74	nM	PMID[22705001]
NPT306	Cell line	PC-3	Homo sapiens	GI50	n.a.	17988.71	nM	PMID[27212070]
NPT146	Cell line	SK-OV-3	Homo sapiens	GI50	n.a.	8203.52	nM	DOI[10.1016/S0960-894X(01)80881-7]
NPT396	Cell line	T47D	Homo sapiens	GI50	n.a.	2857.59	nM	PubChem BioAssay data set
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	n.a.	17782.79	nM	PMID[6539809]
NPT398	Cell line	UACC-62	Homo sapiens	GI50	n.a.	21777.1	nM	PubChem BioAssay data set
NPT400	Cell line	MDA-MB-435	Homo sapiens	GI50	n.a.	4688.13	nM	PMID[20411974]
NPT308	Cell line	CAKI-1	Homo sapiens	GI50	n.a.	40364.54	nM	PMID[24571273]
NPT399	Cell line	SF-295	Homo sapiens	GI50	n.a.	22029.26	nM	PMID[24709561]
NPT402	Cell line	Hs-578T	Homo sapiens	GI50	n.a.	3013.01	nM	DrugMatrix in vivo data: Hematology
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	n.a.	3147.75	nM	Open TG-GATES in vivo data: Hematology
NPT401	Cell line	786-0	Homo sapiens	GI50	n.a.	25409.73	nM	PMID[7473578]
NPT403	Cell line	UACC-257	Homo sapiens	GI50	n.a.	32062.69	nM	PMID[10425118]
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	n.a.	16943.38	nM	PubChem BioAssay data set
NPT405	Cell line	NCI-H226	Homo sapiens	GI50	n.a.	20653.8	nM	PMID[22472691]
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	n.a.	32210.69	nM	PMID[17850214]
NPT139	Cell line	HT-29	Homo sapiens	GI50	n.a.	23550.49	nM	Open TG-GATES in vivo data: Biochemistry
NPT406	Cell line	RXF 393	Homo sapiens	GI50	n.a.	17378.01	nM	Open TG-GATES in vivo data: Hematology
NPT407	Cell line	COLO 205	Homo sapiens	GI50	n.a.	25763.21	nM	PMID[2095372]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	3294.4	nM	DOI[10.1007/s00044-013-0779-x]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	165.1	nM	PMID[20553004]
NPT2	Others	Unspecified	n.a.	IC50	=	10000.0	nM	PMID[25316316]
NPT2	Others	Unspecified	n.a.	Potency	=	20596.2	nM	DOI[10.3390/molecules16075618]
NPT2	Others	Unspecified	n.a.	IC50	>	79000.0	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	IC50	=	12100.0	nM	PMID[20022253]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	10000.0	nM	PMID[11902656]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	11220.2	nM	PMID[16499313]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	15848.9	nM	PMID[2292684]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	8912.5	nM	PMID[23999046]

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 NPC7846 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	29321
0.1-0.2	17622
0.2-0.3	2369
0.3-0.4	376
0.4-0.5	106
0.5-0.6	42
0.6-0.7	8
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	Natural Product ID
0.7925	Intermediate Similarity	NPC143828
0.75	Intermediate Similarity	NPC235215
0.75	Intermediate Similarity	NPC4481
0.7407	Intermediate Similarity	NPC292107
0.7368	Intermediate Similarity	NPC19687
0.7321	Intermediate Similarity	NPC178854
0.7273	Intermediate Similarity	NPC105242
0.7193	Intermediate Similarity	NPC224137
0.7193	Intermediate Similarity	NPC2476
0.7143	Intermediate Similarity	NPC22472
0.7018	Intermediate Similarity	NPC176300
0.6727	Remote Similarity	NPC201547
0.6441	Remote Similarity	NPC115798
0.6333	Remote Similarity	NPC603596
0.619	Remote Similarity	NPC603082
0.6066	Remote Similarity	NPC236769
0.6066	Remote Similarity	NPC605494
0.6034	Remote Similarity	NPC7973
0.6034	Remote Similarity	NPC250822
0.5938	Remote Similarity	NPC76482
0.5833	Remote Similarity	NPC176775
0.5833	Remote Similarity	NPC32557
0.5806	Remote Similarity	NPC189179
0.5797	Remote Similarity	NPC280493
0.5763	Remote Similarity	NPC259058
0.5763	Remote Similarity	NPC607530
0.5667	Remote Similarity	NPC299923
0.5645	Remote Similarity	NPC257914
0.5574	Remote Similarity	NPC110070
0.5574	Remote Similarity	NPC608038
0.5556	Remote Similarity	NPC78302
0.5556	Remote Similarity	NPC474520
0.5556	Remote Similarity	NPC196439
0.5556	Remote Similarity	NPC603112
0.5484	Remote Similarity	NPC163780
0.5484	Remote Similarity	NPC134677
0.5469	Remote Similarity	NPC152166
0.541	Remote Similarity	NPC189960
0.5397	Remote Similarity	NPC204854
0.5397	Remote Similarity	NPC69394
0.5397	Remote Similarity	NPC608498
0.5323	Remote Similarity	NPC231018
0.5323	Remote Similarity	NPC605144
0.5323	Remote Similarity	NPC610359
0.5312	Remote Similarity	NPC25495
0.5312	Remote Similarity	NPC288669
0.5246	Remote Similarity	NPC472438
0.5238	Remote Similarity	NPC201136
0.5238	Remote Similarity	NPC607913
0.5231	Remote Similarity	NPC261004
0.5231	Remote Similarity	NPC227325
0.5161	Remote Similarity	NPC191459
0.5161	Remote Similarity	NPC310259
0.5156	Remote Similarity	NPC183597
0.5156	Remote Similarity	NPC238405
0.5156	Remote Similarity	NPC265511
0.5147	Remote Similarity	NPC99671
0.5079	Remote Similarity	NPC76376
0.5079	Remote Similarity	NPC130894
0.5079	Remote Similarity	NPC101830
0.5079	Remote Similarity	NPC606763

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC7846 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5404
0.1-0.2	3681
0.2-0.3	59
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	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