NPASS Compound

Natural Product: NPC265782

Natural Product ID	NPC265782
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	E-Guggulsterone
IUPAC Name	(8R,9S,10R,13S,14S,17E)-17-ethylidene-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthrene-3,16-dione
Synonyms	(E)-Guggulsterone
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL402063
PubChem CID	6439929
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003568] Androstane steroids [CHEMONTID:0001467] Androgens and derivatives

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 51 54 0 0 0 0 0 0 0 0999 V2000 3.9575 1.6205 1.8929 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2550 1.1605 0.5444 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4126 0.3700 -0.0714 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6274 -0.1569 -1.4556 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7390 -0.1665 -2.0857 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3325 -0.6691 -1.9806 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3742 -0.0503 -1.0156 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0201 -0.6793 -0.9854 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7481 -0.3395 -2.2029 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7647 0.7411 -2.0998 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5911 0.6846 -0.8855 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6630 1.4244 -0.7875 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4897 1.3780 0.4118 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3899 2.2395 0.5743 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2326 0.3066 1.3996 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7105 0.1866 1.5344 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1428 -0.2342 0.1973 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.6152 -1.6348 -0.0778 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6634 -0.0823 0.2309 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0387 -0.5247 1.4615 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3900 0.2348 1.4671 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1410 -0.2102 0.3052 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4221 -1.7126 0.4741 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0100 0.8295 2.6682 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1049 2.3158 1.9966 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8365 2.2847 2.1879 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1640 1.4385 -0.0082 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1901 -0.1528 -2.9737 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2841 -1.7522 -2.0646 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2789 1.0176 -1.1996 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0553 -1.7901 -0.9214 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0281 -0.0392 -2.9930 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2830 -1.2344 -2.6339 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3810 0.6951 -3.0342 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2021 1.7180 -2.1560 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9955 2.1075 -1.5831 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5737 -0.6486 0.9718 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6609 0.5161 2.3963 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3408 1.1886 1.8089 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5003 -0.6019 2.2755 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8286 -2.3342 -0.3591 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1300 -2.0874 0.8185 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4173 -1.6152 -0.8655 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4590 1.0294 0.1416 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1656 -1.5954 1.6003 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5200 -0.1543 2.3608 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0466 1.2894 1.4632 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8525 -0.1065 2.3998 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1960 -2.0158 -0.2602 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8832 -1.8481 1.4823 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5536 -2.3403 0.3194 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 4 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 1 0 16 17 1 0 17 18 1 6 17 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 1 22 3 1 0 22 7 1 0 19 8 1 0 17 11 1 0 1 24 1 0 1 25 1 0 1 26 1 0 2 27 1 0 6 28 1 0 6 29 1 0 7 30 1 6 8 31 1 1 9 32 1 0 9 33 1 0 10 34 1 0 10 35 1 0 12 36 1 0 15 37 1 0 15 38 1 0 16 39 1 0 16 40 1 0 18 41 1 0 18 42 1 0 18 43 1 0 19 44 1 6 20 45 1 0 20 46 1 0 21 47 1 0 21 48 1 0 23 49 1 0 23 50 1 0 23 51 1 0 M END

Standard InCHIKey	WDXRGPWQVHZTQJ-AUKWTSKRSA-N
Standard InCHI	InChI=1S/C21H28O2/c1-4-16-19(23)12-18-15-6-5-13-11-14(22)7-9-20(13,2)17(15)8-10-21(16,18)3/h4,11,15,17-18H,5-10,12H2,1-3H3/b16-4-/t15-,17+,18+,20+,21-/m1/s1
SMILES	C/C=C1/C(=O)C[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	312.21	Volume:	344.581 ? Van der Waals volume.
Dense:	0.906	LogP:	2.893 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.94 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.578 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	23.0
TPSA:	34.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.61	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.22	Fsp³:	0.714
MCE-18:	66.667 ? 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:	0.484	Fluc inhibitor:	0.038 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.013 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.664	Promiscuous compounds:	0.919

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.513	MDCK Permeability:	-4.796
Pgp-inhibitor:	0.996	Pgp-substrate:	0.001
PAMPA:	0.003 ? 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%):	0.088	30% Bioavailability (F30%):	0.355
50% Bioavailability (F50%):	0.904

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.024	MRP1:	0.372
Plasma Protein Binding (PPB):	97.64%	Volume Distribution (VD):	-0.091
Fu:	2.541% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.77
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.304	CYP1A2-substrate:	0.978
CYP2C19-inhibitor:	0.998	CYP2C19-substrate:	0.347
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.484
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.997
HLM stability:	0.918 ? 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):

9.815

Half-life (T1/2):

0.252

ADMET: Toxicity

hERG Blockers:	0.101	hERG Blockers (10um):	0.4
Human Hepatotoxicity (H-HT):	0.71	Drug-induced Liver Injury (DILI):	0.438
AMES Toxicity:	0.363	Rat Oral Acute Toxicity:	0.581
Maximum Recommended Daily Dose:	0.731	Skin Sensitization:	0.86
Carcinogencity:	0.945	Eye Corrosion:	0.025
Eye Irritation:	0.593	Respiratory Toxicity:	0.515
Drug-induced Neurotoxicity:	0.642	Ototoxicity:	0.373
Hematotoxicity:	0.559	Drug-induced Nephrotoxicity:	0.505
Genotoxicity:	0.953	RPMI-8226 Immunitoxicity:	0.113
A549 Cytotoxicity:	0.19	Hek293 Cytotoxicity:	0.558
BCF:	1.181 ? 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:	3.839 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.277 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.763 ? 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
NPO32667	Petrosia sp.	Species	Petrosiidae	Eukaryota	n.a.	(15-25 m depth) off Komun Island, Korea	1995-JUL	PMID[10217707]
NPO32667	Petrosia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[10346968]
NPO32667	Petrosia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11170665]
NPO32667	Petrosia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11754614]
NPO32667	Petrosia sp.	Species	Petrosiidae	Eukaryota	n.a.	Indonesia	1996	PMID[18327911]
NPO13567	Streptomyces sahachiroi	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[20485749]
NPO32667	Petrosia sp.	Species	Petrosiidae	Eukaryota	n.a.	Miyako sea-knoll, southwestern Japan (2525.64' N, 12542.48' E), at a depth of 415 m	2009-OCT	PMID[21534590]
NPO32667	Petrosia sp.	Species	Petrosiidae	Eukaryota	n.a.	American Samoa	n.a.	PMID[23368996]
NPO32667	Petrosia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[26821210]
NPO32667	Petrosia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9917297]
NPO16197	Eucalyptus microcorys	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16527	Baptisia minor	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO32667	Petrosia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13567	Streptomyces sahachiroi	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16488	Achromobacter piechaudii	Species	Alcaligenaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO13402	Eupatorium inulifolium	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16527	Baptisia minor	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16197	Eucalyptus microcorys	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13567	Streptomyces sahachiroi	Species	Streptomycetaceae	Bacteria	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	101
IC50	30
Ki	6
EC50	21
Efficacy	7
log2FC	22
PC50	2

Activity Type	# Activity
Individual protein	107
Cell line	34
Protein-protein interaction	1
Protein complex	2
Protein family	4
Others	30
Tissue	11

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT153	Individual protein	Androgen Receptor	Homo sapiens	Potency	n.a.	2448.1	nM	PubChem BioAssay data set
NPT153	Individual protein	Androgen Receptor	Homo sapiens	Potency	n.a.	8608.6	nM	PubChem BioAssay data set
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	Potency	n.a.	60944.1	nM	PubChem BioAssay data set
NPT106	Individual protein	Peroxisome proliferator-activated receptor delta	Homo sapiens	Potency	n.a.	21818.9	nM	PubChem BioAssay data set
NPT162	Individual protein	Heat shock protein beta-1	Homo sapiens	Potency	n.a.	19446.1	nM	PubChem BioAssay data set
NPT106	Individual protein	Peroxisome proliferator-activated receptor delta	Homo sapiens	Potency	n.a.	6149.4	nM	PubChem BioAssay data set
NPT163	Individual protein	Nuclear factor NF-kappa-B p105 subunit	Homo sapiens	Potency	n.a.	30820	nM	PubChem BioAssay data set
NPT249	Individual protein	Glucocorticoid receptor	Homo sapiens	Ki	=	224.0	nM	PMID[16250653]
NPT153	Individual protein	Androgen Receptor	Homo sapiens	Ki	=	240.0	nM	PMID[16250653]
NPT249	Individual protein	Glucocorticoid receptor	Homo sapiens	IC50	=	1740.0	nM	PMID[16250653]
NPT153	Individual protein	Androgen Receptor	Homo sapiens	IC50	=	220.0	nM	PMID[16250653]
NPT210	Individual protein	Thyroid stimulating hormone receptor	Homo sapiens	Potency	=	15848.9	nM	PubChem BioAssay data set
NPT282	Individual protein	MAP kinase ERK2	Homo sapiens	Potency	=	31622.8	nM	PubChem BioAssay data set
NPT150	Individual protein	Anthrax lethal factor	Bacillus anthracis	Potency	=	31622.8	nM	PubChem BioAssay data set
NPT109	Individual protein	Cytochrome P450 3A4	Homo sapiens	Potency	=	1000.0	nM	PubChem BioAssay data set
NPT108	Individual protein	Estrogen receptor alpha	Homo sapiens	Potency	n.a.	39810.7	nM	PubChem BioAssay data set
NPT249	Individual protein	Glucocorticoid receptor	Homo sapiens	Potency	n.a.	11220.2	nM	PubChem BioAssay data set
NPT153	Individual protein	Androgen Receptor	Homo sapiens	Potency	n.a.	44668.4	nM	PubChem BioAssay data set
NPT106	Individual protein	Peroxisome proliferator-activated receptor delta	Homo sapiens	Potency	n.a.	22387.2	nM	PubChem BioAssay data set
NPT108	Individual protein	Estrogen receptor alpha	Homo sapiens	Potency	n.a.	19952.6	nM	PubChem BioAssay data set
NPT106	Individual protein	Peroxisome proliferator-activated receptor delta	Homo sapiens	Potency	n.a.	28183.8	nM	PubChem BioAssay data set
NPT198	Individual protein	Vitamin D receptor	Homo sapiens	Potency	n.a.	50118.7	nM	PubChem BioAssay data set
NPT249	Individual protein	Glucocorticoid receptor	Homo sapiens	Potency	n.a.	35481.3	nM	PubChem BioAssay data set
NPT198	Individual protein	Vitamin D receptor	Homo sapiens	Potency	n.a.	31622.8	nM	PubChem BioAssay data set
NPT163	Individual protein	Nuclear factor NF-kappa-B p105 subunit	Homo sapiens	Potency	n.a.	50118.7	nM	PubChem BioAssay data set
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	Potency	n.a.	3757.8	nM	PubChem BioAssay data set
NPT158	Individual protein	Nuclear receptor subfamily 1 group I member 2	Rattus norvegicus	Potency	n.a.	12589.3	nM	PubChem BioAssay data set
NPT102	Individual protein	Interleukin-8	Homo sapiens	Potency	n.a.	66824.2	nM	PubChem BioAssay data set
NPT103	Individual protein	Nuclear receptor ROR-gamma	Homo sapiens	Potency	n.a.	47307.9	nM	PubChem BioAssay data set
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	Potency	n.a.	42163.2	nM	PubChem BioAssay data set
NPT1794	Individual protein	LXR-alpha	Homo sapiens	EC50	>	100000.0	nM	PMID[31673308]
NPT1794	Individual protein	LXR-alpha	Homo sapiens	IC50	>	100000.0	nM	PMID[31673308]
NPT1746	Individual protein	LXR-beta	Homo sapiens	EC50	=	3600.0	nM	PMID[31673308]
NPT1746	Individual protein	LXR-beta	Homo sapiens	IC50	>	100000.0	nM	PMID[31673308]
NPT106	Individual protein	Peroxisome proliferator-activated receptor delta	Homo sapiens	EC50	>	100000.0	nM	PMID[31673308]
NPT106	Individual protein	Peroxisome proliferator-activated receptor delta	Homo sapiens	IC50	>	100000.0	nM	PMID[31673308]
NPT198	Individual protein	Vitamin D receptor	Homo sapiens	EC50	>	100000.0	nM	PMID[31673308]
NPT198	Individual protein	Vitamin D receptor	Homo sapiens	IC50	=	2000.0	nM	PMID[31673308]
NPT108	Individual protein	Estrogen receptor alpha	Homo sapiens	EC50	>	100000.0	nM	PMID[31673308]
NPT108	Individual protein	Estrogen receptor alpha	Homo sapiens	IC50	=	62000.0	nM	PMID[31673308]
NPT249	Individual protein	Glucocorticoid receptor	Homo sapiens	EC50	>	100000.0	nM	PMID[31673308]
NPT249	Individual protein	Glucocorticoid receptor	Homo sapiens	IC50	>	100000.0	nM	PMID[31673308]
NPT1746	Individual protein	LXR-beta	Homo sapiens	Efficacy	=	40.0	%	PMID[31673308]
NPT2612	Individual protein	Bile acid receptor	Mus musculus	log2FC	=	1.6	n.a.	PMID[31673308]
NPT2612	Individual protein	Bile acid receptor	Mus musculus	log2FC	=	1.3	n.a.	PMID[31673308]
NPT2612	Individual protein	Bile acid receptor	Mus musculus	log2FC	=	1.2	n.a.	PMID[31673308]
NPT2612	Individual protein	Bile acid receptor	Mus musculus	log2FC	=	-1.0	n.a.	PMID[31673308]
NPT2612	Individual protein	Bile acid receptor	Mus musculus	log2FC	=	-1.1	n.a.	PMID[31673308]
NPT2612	Individual protein	Bile acid receptor	Mus musculus	log2FC	=	-1.2	n.a.	PMID[31673308]
NPT2612	Individual protein	Bile acid receptor	Mus musculus	log2FC	=	-1.5	n.a.	PMID[31673308]
NPT2612	Individual protein	Bile acid receptor	Mus musculus	log2FC	=	-1.4	n.a.	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	IC50	=	100000.0	nM	PMID[16250653]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	Ki	>	5000.0	nM	PMID[16250653]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	IC50	=	4100.0	nM	PMID[17988093]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	IC50	=	44000.0	nM	PMID[21142112]
NPT533	Protein-protein interaction	Runt-related transcription factor 1/Core-binding factor subunit beta	Homo sapiens	Potency	n.a.	15848.9	nM	PubChem BioAssay data set
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	Potency	n.a.	39810.7	nM	PubChem BioAssay data set
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	Potency	n.a.	2511.9	nM	PubChem BioAssay data set
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	IC50	=	41000.0	nM	PMID[26821210]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	EC50	>	100000.0	nM	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	IC50	=	25000.0	nM	PMID[31673308]
NPT866	Individual protein	Peroxisome proliferator-activated receptor alpha	Homo sapiens	EC50	>	100000.0	nM	PMID[31673308]
NPT866	Individual protein	Peroxisome proliferator-activated receptor alpha	Homo sapiens	IC50	=	20000.0	nM	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	EC50	=	220.0	nM	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	EC50	=	310.0	nM	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	EC50	=	420.0	nM	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	EC50	=	130.0	nM	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	EC50	=	400.0	nM	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	EC50	=	380.0	nM	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	IC50	=	13000.0	nM	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	IC50	=	6000.0	nM	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	IC50	=	10000.0	nM	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	IC50	=	4200.0	nM	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	Efficacy	=	46.0	%	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	Efficacy	=	75.0	%	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	Efficacy	=	51.0	%	PMID[31673308]
NPT540	Individual protein	Bile acid receptor FXR	Homo sapiens	Efficacy	=	69.0	%	PMID[31673308]
NPT542	Individual protein	Progesterone receptor	Homo sapiens	Ki	=	201.0	nM	PMID[16250653]
NPT542	Individual protein	Progesterone receptor	Homo sapiens	IC50	=	1200.0	nM	PMID[16250653]
NPT94	Individual protein	Aldehyde dehydrogenase 1A1	Homo sapiens	Potency	=	39810.7	nM	PubChem BioAssay data set
NPT98	Individual protein	HERG	Homo sapiens	Potency	n.a.	17782.8	nM	PubChem BioAssay data set
NPT99	Individual protein	Peroxisome proliferator-activated receptor gamma	Homo sapiens	Potency	n.a.	44668.4	nM	PubChem BioAssay data set
NPT99	Individual protein	Peroxisome proliferator-activated receptor gamma	Homo sapiens	Potency	n.a.	22387.2	nM	PubChem BioAssay data set
NPT99	Individual protein	Peroxisome proliferator-activated receptor gamma	Homo sapiens	EC50	>	100000.0	nM	PMID[31673308]
NPT99	Individual protein	Peroxisome proliferator-activated receptor gamma	Homo sapiens	IC50	=	27000.0	nM	PMID[31673308]
NPT542	Individual protein	Progesterone receptor	Homo sapiens	EC50	=	1900.0	nM	PMID[31673308]
NPT542	Individual protein	Progesterone receptor	Homo sapiens	IC50	>	100000.0	nM	PMID[31673308]
NPT542	Individual protein	Progesterone receptor	Homo sapiens	Efficacy	=	115.0	%	PMID[31673308]
NPT93	Individual protein	Survival motor neuron protein	Homo sapiens	Potency	=	25118.9	nM	PubChem BioAssay data set
NPT46	Individual protein	Thyroid hormone receptor beta-1	Homo sapiens	Potency	n.a.	44668.4	nM	PubChem BioAssay data set
NPT5121	Protein complex	Thyroid hormone receptor	Homo sapiens	EC50	>	100000.0	nM	PMID[31673308]
NPT5121	Protein complex	Thyroid hormone receptor	Homo sapiens	IC50	>	100000.0	nM	PMID[31673308]
NPT541	Individual protein	Mineralocorticoid receptor	Homo sapiens	Ki	=	39.0	nM	PMID[16250653]
NPT543	Individual protein	Pregnane X receptor	Homo sapiens	IC50	=	2.4	nM	PMID[16250653]
NPT544	Protein family	Estrogen receptor	Homo sapiens	IC50	>	5000.0	nM	PMID[16250653]
NPT541	Individual protein	Mineralocorticoid receptor	Homo sapiens	IC50	=	1000.0	nM	PMID[16250653]
NPT544	Protein family	Estrogen receptor	Homo sapiens	Ki	>	5000.0	nM	PMID[16250653]
NPT539	Individual protein	Cellular tumor antigen p53	Homo sapiens	Potency	=	31622.8	nM	PubChem BioAssay data set
NPT546	Individual protein	Retinoid X receptor alpha	Homo sapiens	Potency	n.a.	35481.3	nM	PubChem BioAssay data set
NPT546	Individual protein	Retinoid X receptor alpha	Homo sapiens	Potency	n.a.	25118.9	nM	PubChem BioAssay data set
NPT541	Individual protein	Mineralocorticoid receptor	Homo sapiens	EC50	>	100000.0	nM	PMID[31673308]
NPT541	Individual protein	Mineralocorticoid receptor	Homo sapiens	IC50	=	320.0	nM	PMID[31673308]
NPT543	Individual protein	Pregnane X receptor	Homo sapiens	EC50	=	2500.0	nM	PMID[31673308]
NPT543	Individual protein	Pregnane X receptor	Homo sapiens	IC50	>	100000.0	nM	PMID[31673308]
NPT546	Individual protein	Retinoid X receptor alpha	Homo sapiens	EC50	>	100000.0	nM	PMID[31673308]
NPT546	Individual protein	Retinoid X receptor alpha	Homo sapiens	IC50	=	33000.0	nM	PMID[31673308]
NPT543	Individual protein	Pregnane X receptor	Homo sapiens	Efficacy	=	155.0	%	PMID[31673308]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT347	Cell line	Lymphoblastoid cells	Homo sapiens	Potency	=	50118.7	nM	PubChem BioAssay data set
NPT347	Cell line	Lymphoblastoid cells	Homo sapiens	Potency	=	39810.7	nM	PubChem BioAssay data set
NPT347	Cell line	Lymphoblastoid cells	Homo sapiens	Potency	=	31622.8	nM	PubChem BioAssay data set
NPT347	Cell line	Lymphoblastoid cells	Homo sapiens	Potency	=	79432.8	nM	PubChem BioAssay data set
NPT461	Cell line	PANC-1	Homo sapiens	PC50	=	42.0	uM	PMID[32057581]
NPT461	Cell line	PANC-1	Homo sapiens	IC50	>	100000.0	nM	PMID[32057581]
NPT461	Cell line	PANC-1	Homo sapiens	PC50	n.a.	n.a.	n.a.	PMID[34942553]
NPT24629	Protein family	Retinoic acid receptor	Homo sapiens	EC50	>	100000.0	nM	PMID[31673308]
NPT24629	Protein family	Retinoic acid receptor	Homo sapiens	IC50	>	100000.0	nM	PMID[31673308]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	48846.4	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	34271.4	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	61494	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	8686.3	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	43145.1	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	15446.6	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	50118.7	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	27468.4	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	9659	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	10935.4	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	3458.1	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	21818.9	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	13643.7	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	68380.4	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	76724.1	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	21623.8	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	54316.5	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	19272.2	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	54806.6	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	609.4	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	60944.1	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	=	50118.7	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	=	31622.8	nM	PubChem BioAssay data set
NPT625	Tissue	Liver	Mus musculus	log2FC	=	0.9	n.a.	PMID[31673308]
NPT625	Tissue	Liver	Mus musculus	log2FC	=	0.7	n.a.	PMID[31673308]
NPT625	Tissue	Liver	Mus musculus	log2FC	=	1.0	n.a.	PMID[31673308]
NPT625	Tissue	Liver	Mus musculus	log2FC	=	0.5	n.a.	PMID[31673308]
NPT625	Tissue	Liver	Mus musculus	log2FC	=	-0.3	n.a.	PMID[31673308]
NPT625	Tissue	Liver	Mus musculus	log2FC	=	-0.2	n.a.	PMID[31673308]
NPT625	Tissue	Liver	Mus musculus	log2FC	=	-0.6	n.a.	PMID[31673308]
NPT625	Tissue	Liver	Mus musculus	log2FC	=	0.4	n.a.	PMID[31673308]

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 NPC265782 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	24227
0.1-0.2	24015
0.2-0.3	1505
0.3-0.4	58
0.4-0.5	22
0.5-0.6	21
0.6-0.7	4
0.7-0.8	0
0.8-0.85	0
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	NPC2634
1.0	High Similarity	NPC251929
0.6327	Remote Similarity	NPC139397
0.62	Remote Similarity	NPC307176
0.62	Remote Similarity	NPC321874
0.6154	Remote Similarity	NPC282593
0.5849	Remote Similarity	NPC214043
0.5849	Remote Similarity	NPC227064
0.5849	Remote Similarity	NPC85774
0.5849	Remote Similarity	NPC329043
0.5849	Remote Similarity	NPC58841
0.5849	Remote Similarity	NPC161423
0.5818	Remote Similarity	NPC303613
0.5741	Remote Similarity	NPC35734
0.5741	Remote Similarity	NPC144258
0.5741	Remote Similarity	NPC159577
0.5741	Remote Similarity	NPC115023
0.5741	Remote Similarity	NPC327115
0.5741	Remote Similarity	NPC602429
0.5636	Remote Similarity	NPC149203
0.5636	Remote Similarity	NPC237712
0.5536	Remote Similarity	NPC249312
0.5536	Remote Similarity	NPC323765
0.5439	Remote Similarity	NPC310010
0.5439	Remote Similarity	NPC326627
0.5172	Remote Similarity	NPC119416
0.5082	Remote Similarity	NPC320514

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC265782 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7188
0.1-0.2	1757
0.2-0.3	126
0.3-0.4	52
0.4-0.5	11
0.5-0.6	8
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD4691	Approved
0.62	Remote Similarity	NPD4747	Phase 4
0.5849	Remote Similarity	NPD3666	Phase 4
0.5849	Remote Similarity	NPD4221	Phase 4
0.5536	Remote Similarity	NPD4693	Phase 3
0.5439	Remote Similarity	NPD4753	Phase 2
0.5439	Remote Similarity	NPD5330	Phase 4
0.5345	Remote Similarity	NPD5737	Phase 4
0.5254	Remote Similarity	NPD6409	Approved
0.5167	Remote Similarity	NPD6672	Phase 4

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