NPASS Compound

Natural Product: NPC154304

Natural Product ID	NPC154304
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Rhuschalcone Iv
IUPAC Name	(E)-1-[2-hydroxy-4-[4-hydroxy-5-[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]-2-methoxyphenoxy]phenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one
Synonyms	rhuschalcone IV
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL511428
PubChem CID	5472699
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0003467] Linear 1,3-diarylpropanoids [CHEMONTID:0001630] Chalcones and dihydrochalcones [CHEMONTID:0003472] 2'-Hydroxychalcones

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 63 66 0 0 0 0 0 0 0 0999 V2000 -0.0540 -3.5901 0.5971 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0506 -2.5441 -0.3563 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1245 -1.8120 -0.5378 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2569 -2.0986 0.1927 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4547 -1.3871 0.0394 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5407 -1.7372 0.8087 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5496 -0.3557 -0.8626 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3870 -0.0819 -1.5940 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2088 -0.7828 -1.4422 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1034 -0.4408 -2.2120 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1155 -0.0239 -1.7341 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2279 1.3171 -1.3718 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4233 1.7901 -0.8890 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5439 0.9952 -0.7392 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4105 -0.3116 -1.0998 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2026 -0.8272 -1.5971 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4462 -1.2219 -1.0041 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7443 1.5613 -0.2335 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7116 2.8130 0.0655 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0189 0.9270 -0.0017 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0755 1.5581 0.4765 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3741 0.9872 0.7312 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6722 -0.3281 0.4961 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.9456 -0.8465 0.7555 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.9285 -0.0305 1.2570 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.6488 1.2917 1.4994 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.3848 1.7782 1.2349 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.2168 -0.5330 1.5249 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7403 0.4394 -1.0952 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6720 1.3614 -1.9646 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0147 0.2825 -0.4249 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0523 1.0730 -0.7165 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3506 0.9774 -0.0922 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3449 1.8655 -0.4892 C 0 0 0 0 0 0 0 0 0 0 0 0 10.6088 1.8529 0.0454 C 0 0 0 0 0 0 0 0 0 0 0 0 10.8989 0.9253 1.0097 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9580 0.0252 1.4396 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6825 0.0722 0.8691 C 0 0 0 0 0 0 0 0 0 0 0 0 12.1599 0.8434 1.6062 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0008 -4.1294 0.6221 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7868 -4.2803 0.2974 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2510 -3.2233 1.6187 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1914 -2.9128 0.9088 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5730 -1.7498 1.8023 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4495 0.7358 -2.3144 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3593 1.9805 -1.4766 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4297 2.8600 -0.6256 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1580 -1.8834 -1.8810 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4643 -1.9120 -0.2672 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1455 -0.1096 -0.2197 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9304 2.6149 0.6935 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8914 -0.9703 0.0991 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1017 -1.8915 0.5442 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.4448 1.9119 1.8953 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1892 2.8389 1.4383 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.7264 -1.0625 0.8413 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2277 -0.4543 0.3350 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8557 1.8336 -1.4912 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0929 2.5957 -1.2582 H 0 0 0 0 0 0 0 0 0 0 0 0 11.3865 2.5482 -0.2655 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1524 -0.7247 2.2024 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9575 -0.6473 1.2240 H 0 0 0 0 0 0 0 0 0 0 0 0 13.0042 0.9504 1.0860 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 1 0 5 7 2 0 7 8 1 0 8 9 2 0 9 10 1 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 14 18 1 0 18 19 2 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 25 28 1 0 7 29 1 0 29 30 2 0 29 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 36 37 1 0 37 38 2 0 36 39 1 0 9 3 1 0 16 11 1 0 27 22 1 0 38 33 1 0 1 40 1 0 1 41 1 0 1 42 1 0 4 43 1 0 6 44 1 0 8 45 1 0 12 46 1 0 13 47 1 0 16 48 1 0 17 49 1 0 20 50 1 0 21 51 1 0 23 52 1 0 24 53 1 0 26 54 1 0 27 55 1 0 28 56 1 0 31 57 1 0 32 58 1 0 34 59 1 0 35 60 1 0 37 61 1 0 38 62 1 0 39 63 1 0 M END

Standard InCHIKey	AUWRGBKFYMBVIY-MKFXEVHTSA-N
Standard InCHI	InChI=1S/C31H24O8/c1-38-30-18-29(37)25(27(35)15-7-20-4-10-22(33)11-5-20)17-31(30)39-23-12-13-24(28(36)16-23)26(34)14-6-19-2-8-21(32)9-3-19/h2-18,32-33,36-37H,1H3/b14-6+,15-7+
SMILES	COc1cc(O)c(cc1Oc1ccc(c(c1)O)C(=O)/C=C/c1ccc(cc1)O)C(=O)/C=C/c1ccc(cc1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	524.15	Volume:	538.645 ? Van der Waals volume.
Dense:	0.973	LogP:	4.211 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.278 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.956 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	28.0
TPSA:	133.52 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	4.0	Rings:	4.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.152	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.665	Fsp³:	0.032
MCE-18:	25.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	1.0	Fluc inhibitor:	1.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.872 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.99 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.643	Promiscuous compounds:	0.561

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.885	MDCK Permeability:	-4.822
Pgp-inhibitor:	0.454	Pgp-substrate:	0.001
PAMPA:	0.084 ? 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):	0.0
20% Bioavailability (F20%):	0.86	30% Bioavailability (F30%):	0.971
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.002
Plasma Protein Binding (PPB):	97.323%	Volume Distribution (VD):	-0.416
Fu:	1.713% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.855
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.997
CYP2C9-inhibitor:	0.117	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	0.999	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.039 ? 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):

4.539

Half-life (T1/2):

1.582

ADMET: Toxicity

hERG Blockers:	0.523	hERG Blockers (10um):	0.64
Human Hepatotoxicity (H-HT):	0.674	Drug-induced Liver Injury (DILI):	0.77
AMES Toxicity:	0.259	Rat Oral Acute Toxicity:	0.035
Maximum Recommended Daily Dose:	0.89	Skin Sensitization:	0.93
Carcinogencity:	0.064	Eye Corrosion:	0.0
Eye Irritation:	0.987	Respiratory Toxicity:	0.585
Drug-induced Neurotoxicity:	0.578	Ototoxicity:	0.181
Hematotoxicity:	0.019	Drug-induced Nephrotoxicity:	0.193
Genotoxicity:	0.803	RPMI-8226 Immunitoxicity:	0.08
A549 Cytotoxicity:	0.693	Hek293 Cytotoxicity:	0.979
BCF:	1.32 ? 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:	4.719 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.365 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.142 ? 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
NPO32638	rhus pyroides	Species	Anacardiaceae	Eukaryota	root bark	n.a.	n.a.	PMID[12762790]

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
ED50	1
GI50	58

Activity Type	# Activity
Cell line	59

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT407	Cell line	COLO 205	Homo sapiens	ED50	=	23.0	ug ml-1	DOI[10.6019/CHEMBL1201861]
NPT367	Cell line	MDA-N	Homo sapiens	GI50	n.a.	3206.27	nM	PMID[8277308]
NPT368	Cell line	SN12C	Homo sapiens	GI50	n.a.	2449.06	nM	PMID[19921834]
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	n.a.	2666.86	nM	PMID[17562796]
NPT369	Cell line	ACHN	Homo sapiens	GI50	n.a.	2398.83	nM	PMID[18838581]
NPT371	Cell line	UO-31	Homo sapiens	GI50	n.a.	2564.48	nM	DOI[10.6019/CHEMBL1201861]
NPT116	Cell line	HL-60	Homo sapiens	GI50	n.a.	3647.54	nM	PMID[10579873]
NPT372	Cell line	HOP-92	Homo sapiens	GI50	n.a.	4355.12	nM	PMID[18391949]
NPT90	Cell line	DU-145	Homo sapiens	GI50	n.a.	2290.87	nM	PMID[20384315]
NPT374	Cell line	SF-539	Homo sapiens	GI50	n.a.	2371.37	nM	PMID[17190458]
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	n.a.	1918.67	nM	PMID[20329738]
NPT375	Cell line	Malme-3M	Homo sapiens	GI50	n.a.	2576.32	nM	PMID[25684422]
NPT376	Cell line	A498	Homo sapiens	GI50	n.a.	2046.44	nM	PMID[11908966]
NPT111	Cell line	K562	Homo sapiens	GI50	n.a.	3388.44	nM	PMID[18183025]
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	n.a.	2870.78	nM	PMID[21916509]
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	n.a.	3126.08	nM	PMID[12105963]
NPT379	Cell line	HOP-62	Homo sapiens	GI50	n.a.	4466.84	nM	PMID[18644957]
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	GI50	n.a.	2910.72	nM	PMID[19620329]
NPT380	Cell line	U-251	Homo sapiens	GI50	n.a.	1927.52	nM	PMID[21481593]
NPT381	Cell line	OVCAR-8	Homo sapiens	GI50	n.a.	2594.18	nM	PMID[18579783]
NPT382	Cell line	OVCAR-5	Homo sapiens	GI50	n.a.	2685.34	nM	PMID[17343407]
NPT383	Cell line	SNB-19	Homo sapiens	GI50	n.a.	4528.98	nM	PubChem BioAssay data set
NPT82	Cell line	MDA-MB-231	Homo sapiens	GI50	n.a.	3597.49	nM	PMID[24164206]
NPT385	Cell line	SR	Homo sapiens	GI50	n.a.	2376.84	nM	PMID[17190448]
NPT384	Cell line	TK-10	Homo sapiens	GI50	n.a.	3419.79	nM	PMID[20038128]
NPT323	Cell line	SW-620	Homo sapiens	GI50	n.a.	3357.38	nM	DrugMatrix in vivo data: Pathology
NPT455	Cell line	NCI-H522	Homo sapiens	GI50	n.a.	1936.42	nM	PMID[23043462]
NPT386	Cell line	KM12	Homo sapiens	GI50	n.a.	1442.12	nM	PMID[17353252]
NPT387	Cell line	M14	Homo sapiens	GI50	n.a.	3899.42	nM	PMID[20824690]
NPT389	Cell line	RPMI-8226	Homo sapiens	GI50	n.a.	2338.84	nM	DrugMatrix in vitro pharmacology data
NPT388	Cell line	NCI-H322M	Homo sapiens	GI50	n.a.	2910.72	nM	PMID[10924160]
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	n.a.	3404.08	nM	PMID[15730249]
NPT456	Cell line	OVCAR-4	Homo sapiens	GI50	n.a.	2218.2	nM	PMID[20939516]
NPT457	Cell line	BT-549	Homo sapiens	GI50	n.a.	2917.43	nM	PMID[17004723]
NPT147	Cell line	SK-MEL-2	Homo sapiens	GI50	n.a.	3357.38	nM	Open TG-GATES in vivo data: Hematology
NPT81	Cell line	A549	Homo sapiens	GI50	n.a.	2964.83	nM	PMID[17452481]
NPT392	Cell line	SNB-75	Homo sapiens	GI50	n.a.	4207.27	nM	PMID[22440015]
NPT393	Cell line	HCT-116	Homo sapiens	GI50	n.a.	1798.87	nM	DrugMatrix in vitro pharmacology data
NPT148	Cell line	HCT-15	Homo sapiens	GI50	n.a.	1794.73	nM	PMID[11551759]
NPT395	Cell line	SF-268	Homo sapiens	GI50	n.a.	2964.83	nM	PMID[9722490]
NPT394	Cell line	EKVX	Homo sapiens	GI50	n.a.	2269.86	nM	DOI[10.1007/s00044-012-0025-y]
NPT83	Cell line	MCF7	Homo sapiens	GI50	n.a.	2685.34	nM	PMID[19721064]
NPT306	Cell line	PC-3	Homo sapiens	GI50	n.a.	3784.43	nM	PMID[20585136]
NPT146	Cell line	SK-OV-3	Homo sapiens	GI50	n.a.	2884.03	nM	PMID[16038536]
NPT396	Cell line	T47D	Homo sapiens	GI50	n.a.	2285.6	nM	PMID[19029333]
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	n.a.	2884.03	nM	PMID[15161186]
NPT398	Cell line	UACC-62	Homo sapiens	GI50	n.a.	2328.09	nM	DrugMatrix in vivo data: Pathology
NPT400	Cell line	MDA-MB-435	Homo sapiens	GI50	n.a.	3396.25	nM	PMID[18809939]
NPT308	Cell line	CAKI-1	Homo sapiens	GI50	n.a.	3499.45	nM	PubChem BioAssay data set
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	n.a.	1667.25	nM	DOI[10.6019/CHEMBL1201861]
NPT399	Cell line	SF-295	Homo sapiens	GI50	n.a.	3758.37	nM	PMID[25647077]
NPT402	Cell line	Hs-578T	Homo sapiens	GI50	n.a.	6516.28	nM	PMID[14738383]
NPT401	Cell line	786-0	Homo sapiens	GI50	n.a.	2233.57	nM	PMID[8946743]
NPT403	Cell line	UACC-257	Homo sapiens	GI50	n.a.	6194.41	nM	PMID[23305465]
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	n.a.	2660.73	nM	DOI[10.6019/CHEMBL1201861]
NPT139	Cell line	HT-29	Homo sapiens	GI50	n.a.	1364.58	nM	PMID[18625769]
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	n.a.	1945.36	nM	PMID[19441852]
NPT407	Cell line	COLO 205	Homo sapiens	GI50	n.a.	1879.32	nM	PubChem BioAssay data set
NPT406	Cell line	RXF 393	Homo sapiens	GI50	n.a.	2483.13	nM	PMID[18512986]

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 NPC154304 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	25227
0.1-0.2	19224
0.2-0.3	4961
0.3-0.4	334
0.4-0.5	93
0.5-0.6	15
0.6-0.7	1
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8571	High Similarity	NPC188967
0.8393	Intermediate Similarity	NPC190487
0.6481	Remote Similarity	NPC205468
0.5965	Remote Similarity	NPC119660
0.5873	Remote Similarity	NPC185526
0.55	Remote Similarity	NPC254659
0.5397	Remote Similarity	NPC269694
0.537	Remote Similarity	NPC19174
0.537	Remote Similarity	NPC115159
0.5357	Remote Similarity	NPC139813
0.5345	Remote Similarity	NPC262359
0.5263	Remote Similarity	NPC192304
0.5254	Remote Similarity	NPC284556
0.5238	Remote Similarity	NPC188879
0.5172	Remote Similarity	NPC257756
0.5172	Remote Similarity	NPC64359
0.5167	Remote Similarity	NPC263670
0.5167	Remote Similarity	NPC129132

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC154304 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4871
0.1-0.2	4146
0.2-0.3	132
0.3-0.4	1
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