NPASS Compound

Natural Product: NPC262198

Natural Product ID	NPC262198
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Salvinorin A
IUPAC Name	methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-9-acetyloxy-2-(furan-3-yl)-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octahydro-1H-benzo[f]isochromene-7-carboxylate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL445332
PubChem CID	128563
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001538] Diterpene lactones

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 59 62 0 0 0 0 0 0 0 0999 V2000 -4.4192 -3.1303 1.7324 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6355 -2.1289 1.1258 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7339 -1.4043 1.8625 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6430 -1.6758 3.0933 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8970 -0.3541 1.2797 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.7562 0.7101 0.6913 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9919 1.8134 0.0098 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8335 2.5044 -0.8644 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1556 3.8327 -0.6466 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6595 4.3857 0.3673 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0555 4.5188 -1.6088 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7301 1.3734 -0.6153 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3415 1.9842 -1.5781 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0208 0.2383 -0.0846 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8719 -0.8909 0.2779 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6056 -1.5669 -0.8123 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0705 -1.9562 1.0393 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9423 -2.4642 0.0344 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8957 -1.3430 -0.2260 C 0 0 2 0 0 0 0 0 0 0 0 0 1.2394 -0.1433 -0.8686 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0141 -0.3648 -2.3360 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2588 0.9993 -0.7437 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6516 0.5763 -1.0446 C 0 0 2 0 0 0 0 0 0 0 0 0 3.7196 -0.6841 -1.7032 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0299 -1.7318 -1.1079 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3839 -2.9005 -1.3351 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5399 0.5522 0.1357 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8214 0.0481 0.1662 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2965 0.1976 1.3698 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4316 0.7697 2.1711 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2843 1.0125 1.4046 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0164 -3.6293 0.9365 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0977 -2.6907 2.4994 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7990 -3.9064 2.2326 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2793 0.1312 2.0807 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5668 0.2962 0.0224 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3256 1.1785 1.5278 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6850 2.5285 0.8309 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7949 4.2769 -2.6587 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0128 5.6119 -1.5140 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1067 4.2190 -1.3972 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4358 0.6087 0.9130 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9783 -2.5745 -0.4563 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5564 -1.0426 -1.1248 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0750 -1.7780 -1.7345 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4884 -1.4165 1.8227 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7259 -2.7449 1.4237 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5367 -3.3097 0.4418 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4591 -2.8205 -0.9091 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3165 -1.0100 0.7441 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0893 0.0372 -2.7443 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8373 0.1147 -2.9485 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1422 -1.4615 -2.5843 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1303 1.3992 0.2740 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9964 1.8207 -1.4562 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1540 1.2857 -1.7700 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3634 -0.4042 -0.6682 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5311 1.0250 3.2170 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4100 1.4781 1.8133 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 3 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 9 11 1 0 7 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 15 16 1 6 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 6 20 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 2 0 23 27 1 0 27 28 2 0 28 29 1 0 29 30 1 0 30 31 2 0 15 5 1 0 25 19 1 0 31 27 1 0 20 14 1 0 1 32 1 0 1 33 1 0 1 34 1 0 5 35 1 1 6 36 1 0 6 37 1 0 7 38 1 1 11 39 1 0 11 40 1 0 11 41 1 0 14 42 1 1 16 43 1 0 16 44 1 0 16 45 1 0 17 46 1 0 17 47 1 0 18 48 1 0 18 49 1 0 19 50 1 1 21 51 1 0 21 52 1 0 21 53 1 0 22 54 1 0 22 55 1 0 23 56 1 6 28 57 1 0 30 58 1 0 31 59 1 0 M END

Standard InCHIKey	OBSYBRPAKCASQB-AGQYDFLVSA-N
Standard InCHI	InChI=1S/C23H28O8/c1-12(24)30-16-9-15(20(26)28-4)22(2)7-5-14-21(27)31-17(13-6-8-29-11-13)10-23(14,3)19(22)18(16)25/h6,8,11,14-17,19H,5,7,9-10H2,1-4H3/t14-,15-,16-,17-,19-,22-,23-/m0/s1
SMILES	COC(=O)[C@@H]1C[C@H](OC(=O)C)C(=O)[C@H]2[C@@]1(C)CC[C@@H]1[C@]2(C)C[C@H](OC1=O)c1cocc1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	432.18	Volume:	426.641 ? Van der Waals volume.
Dense:	1.013	LogP:	1.968 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.092 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.937 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	25.0
TPSA:	109.11 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.53	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.625	Fsp³:	0.652
MCE-18:	100.211 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.469	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.015 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.203	Promiscuous compounds:	0.19

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.847	MDCK Permeability:	-4.565
Pgp-inhibitor:	0.871	Pgp-substrate:	0.081
PAMPA:	0.179 ? 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):	0.004
20% Bioavailability (F20%):	0.047	30% Bioavailability (F30%):	0.161
50% Bioavailability (F50%):	0.529

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.93
Plasma Protein Binding (PPB):	56.088%	Volume Distribution (VD):	0.005
Fu:	44.889% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.119
BSEP inhibitor:	0.987

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.92
CYP2C19-inhibitor:	0.997	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.3
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.01
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.959
HLM stability:	0.145 ? 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):

6.506

Half-life (T1/2):

1.117

ADMET: Toxicity

hERG Blockers:	0.034	hERG Blockers (10um):	0.105
Human Hepatotoxicity (H-HT):	0.879	Drug-induced Liver Injury (DILI):	0.993
AMES Toxicity:	0.847	Rat Oral Acute Toxicity:	0.827
Maximum Recommended Daily Dose:	0.915	Skin Sensitization:	0.984
Carcinogencity:	0.929	Eye Corrosion:	0.003
Eye Irritation:	0.58	Respiratory Toxicity:	0.323
Drug-induced Neurotoxicity:	0.58	Ototoxicity:	0.242
Hematotoxicity:	0.385	Drug-induced Nephrotoxicity:	0.967
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.093
A549 Cytotoxicity:	0.434	Hek293 Cytotoxicity:	0.178
BCF:	1.016 ? 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:	3.776 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.012 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.425 ? 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
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14510607]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15987194]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16441078]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16621556]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16945525]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17190459]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17580847]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21338114]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25193297]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36987013]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
Ki	82
EC50	45
Emax	33
Efficacy	4
Ratio EC50	3
Inhibition	12
Potency	6
ED50	7
Selectivity	3
Ratio Ki	29
IC50	1

Activity Type	# Activity
Individual protein	175
Cell line	1
Protein-protein interaction	1
Others	34
Organism	13
Single protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT145	Individual protein	Mu opioid receptor	Homo sapiens	Ki	>	1000.0	nM	PMID[16792410]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	40.0	nM	PMID[25248680]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	120.0	%	PMID[21338114]
NPT271	Individual protein	Delta opioid receptor	Homo sapiens	Ki	=	5790.0	nM	PMID[16792410]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	1.9	nM	PMID[20478711]
NPT145	Individual protein	Mu opioid receptor	Homo sapiens	Ki	>	10000.0	nM	PMID[23587424]
NPT271	Individual protein	Delta opioid receptor	Homo sapiens	Ki	>	10000.0	nM	PMID[23587424]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	38.0	nM	PMID[16033256]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	1.3	nM	PMID[26330078]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	4.5	nM	PMID[26330078]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Efficacy	=	99.0	%	PMID[16777411]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	2.6	nM	PMID[16777411]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	2.2	nM	PMID[16777411]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Efficacy	=	106.0	%	PMID[16945525]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	2.82	nM	PMID[17303418]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	4.77	nM	PMID[17303418]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	100.0	%	PMID[28718638]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	107.0	%	PMID[17303418]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	45.0	nM	PMID[16441078]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	108.0	%	PMID[17580847]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	1.24	nM	PMID[17904842]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	118.0	%	PMID[17904842]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	2.4	nM	PMID[17981041]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	1.8	nM	PMID[17981041]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	81.0	%	PMID[17981041]
NPT1069	Individual protein	Mu opioid receptor	Rattus norvegicus	Ki	>	1000.0	nM	PMID[26330078]
NPT1167	Individual protein	Delta opioid receptor	Mus musculus	Ki	>	1000.0	nM	PMID[26330078]
NPT1069	Individual protein	Mu opioid receptor	Rattus norvegicus	Ki	>	25000.0	nM	PMID[18293909]
NPT1167	Individual protein	Delta opioid receptor	Mus musculus	Ki	>	25000.0	nM	PMID[18293909]
NPT145	Individual protein	Mu opioid receptor	Homo sapiens	Ki	=	4370.0	nM	PMID[18380425]
NPT271	Individual protein	Delta opioid receptor	Homo sapiens	Ki	=	3990.0	nM	PMID[18380425]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	5.7	nM	PMID[18380425]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	2.5	nM	PMID[19147366]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	2.1	nM	PMID[19147366]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	105.0	%	PMID[19147366]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ratio EC50	=	0.1	n.a.	PMID[16441078]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ratio EC50	=	0.2	n.a.	PMID[16441078]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	0.81	nM	PMID[16441078]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	0.8	nM	PMID[19683449]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Inhibition	>	50.0	%	PMID[26330078]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	106.0	%	PMID[20801035]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	7.5	nM	PMID[20801035]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	0.75	nM	PMID[21115248]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	0.2	nM	PMID[21115248]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	703.0	%	PMID[21115248]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	7.4	nM	PMID[22464684]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	ED50	=	40.0	nM	PMID[21338114]
NPT145	Individual protein	Mu opioid receptor	Homo sapiens	EC50	=	2860.0	nM	PMID[21338114]
NPT145	Individual protein	Mu opioid receptor	Homo sapiens	Emax	=	75.0	%	PMID[21338114]
NPT198	Individual protein	Vitamin D receptor	Homo sapiens	Potency	n.a.	44668.4	nM	PubChem BioAssay data set
NPT1069	Individual protein	Mu opioid receptor	Rattus norvegicus	Inhibition	<	50.0	%	PMID[26330078]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	3.0	nM	PMID[22204910]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	6.9	nM	PMID[22204910]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	98.0	%	PMID[22204910]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	31.0	nM	PMID[22204910]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ratio EC50	=	3.0	n.a.	PMID[22204910]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	6.11	nM	PMID[22464684]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	124.0	%	PMID[22464684]
NPT145	Individual protein	Mu opioid receptor	Homo sapiens	Ki	=	1370.0	nM	PMID[22464684]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	97.0	%	PMID[22464684]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	6.2	nM	PMID[23587424]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	5.0	nM	PMID[23587424]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	3.162	nM	PMID[24365159]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	3.2	nM	PMID[24365159]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	16.0	nM	PMID[24559070]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	1.7	nM	PMID[25075762]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	103.0	%	PMID[25075762]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	0.03	nM	PMID[25426797]
NPT145	Individual protein	Mu opioid receptor	Homo sapiens	EC50	>=	10000.0	nM	PMID[25426797]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	2.9	nM	PMID[25193297]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	0.36	nM	PMID[25193297]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	110.0	%	PMID[26330078]
NPT1167	Individual protein	Delta opioid receptor	Mus musculus	Inhibition	>	50.0	%	PMID[26330078]
NPT1069	Individual protein	Mu opioid receptor	Rattus norvegicus	Inhibition	>	50.0	%	PMID[26330078]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	0.21	nM	PMID[28376298]
NPT271	Individual protein	Delta opioid receptor	Homo sapiens	Emax	=	0.0	%	PMID[28376298]
NPT145	Individual protein	Mu opioid receptor	Homo sapiens	Emax	=	0.0	%	PMID[28376298]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	0.042	nM	PMID[28718638]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	94.0	%	PMID[29939744]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	10.0	nM	PMID[29939744]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	101.0	%	PMID[29939744]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	4.7	nM	PMID[29939744]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	0.015	nM	PMID[30543421]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	5.1	nM	PMID[30543421]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Emax	=	99.8	%	PMID[33479684]
NPT145	Individual protein	Mu opioid receptor	Homo sapiens	EC50	>	10000.0	nM	PMID[25426797]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	0.04	nM	PMID[27958743]
NPT271	Individual protein	Delta opioid receptor	Homo sapiens	EC50	>	10000.0	nM	PMID[27958743]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	40.0	nM	PMID[36179400]
NPT1075	Individual protein	Kappa opioid receptor	Cavia porcellus	Ki	>	5000.0	nM	PMID[36179400]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	16.0	nM	PMID[36179400]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	4.73	nM	PMID[36179400]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	10.5	nM	PMID[36179400]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	Ki	=	4.0	nM	PMID[36179400]
NPT1075	Individual protein	Kappa opioid receptor	Cavia porcellus	Ki	=	4.3	nM	PMID[36179400]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	0.2	nM	PMID[36179400]
NPT145	Individual protein	Mu opioid receptor	Homo sapiens	Ki	>	10000.0	nM	PMID[34995453]
NPT271	Individual protein	Delta opioid receptor	Homo sapiens	Ki	>	10000.0	nM	PMID[34995453]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	EC50	=	2.2	nM	PMID[36179400]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	4.0	nM	PMID[15658846]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	0.75	nM	PMID[17303418]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	18.4	nM	PMID[17303418]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	17.5	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	22.0	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	18.1	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	6.8	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	25.3	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	29.6	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	2.9	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	>	10000.0	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	147.0	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	67.0	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	17.7	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	9.5	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	19.5	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	79.0	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	16.0	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	126.0	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	37.0	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	71.0	nM	PMID[18293909]
NPT3601	Individual protein	Kappa opioid receptor	Rattus norvegicus	Ki	=	565.0	nM	PMID[18293909]
NPT50	Individual protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	=	50118.7	nM	PubChem BioAssay data set
NPT50	Individual protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	=	39810.7	nM	PubChem BioAssay data set
NPT533	Protein-protein interaction	Runt-related transcription factor 1/Core-binding factor subunit beta	Homo sapiens	Potency	n.a.	2818.4	nM	PubChem BioAssay data set
NPT20556	Single protein	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	14.76	%	DOI[10.6019/CHEMBL4495564]
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	-64.16	%	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	=	-2.73	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT3603	Individual protein	Kappa opioid receptor	Mus musculus	EC50	=	104.0	nM	PMID[34995453]
NPT3603	Individual protein	Kappa opioid receptor	Mus musculus	EC50	=	6.9	nM	PMID[34995453]
NPT3603	Individual protein	Kappa opioid receptor	Mus musculus	Ki	=	18.7	nM	PMID[34995453]
NPT443	Individual protein	Histone acetyltransferase GCN5	Homo sapiens	Potency	n.a.	39810.7	nM	PubChem BioAssay data set
NPT5	Individual protein	Histone-lysine N-methyltransferase, H3 lysine-9 specific 3	Homo sapiens	Potency	n.a.	17782.8	nM	PubChem BioAssay data set

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	>	100000.0	nM	PMID[25075762]
NPT5131	Others	Opioid receptors; delta & kappa	Homo sapiens	Selectivity	=	3050.0	n.a.	PMID[16033256]
NPT5131	Others	Opioid receptors; delta & kappa	Homo sapiens	Selectivity	>	33.0	n.a.	PMID[16033256]
NPT4121	Organism	Rhesus monkey	Macaca mulatta	ED50	=	0.0037	mg.kg-1	PMID[22464684]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	9.21	%	DOI[10.21203/rs.3.rs-23951/v1]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-0.02	%	DOI[10.6019/CHEMBL4495565]
NPT4390	Others	Opioid receptors; mu & kappa	Homo sapiens	Selectivity	>	33.0	n.a.	PMID[16033256]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	1.26	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	1.0	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	0.39	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	1.45	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	1.69	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	0.17	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	>	500.0	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	8.4	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	3.8	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	0.54	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	1.1	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	4.5	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	0.91	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	7.2	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	2.1	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	32.0	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	4.1	n.a.	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ki	=	458.0	nM	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ki	=	522.0	nM	PMID[18293909]
NPT2	Others	Unspecified	n.a.	Ratio Ki	>	526.0	n.a.	PMID[20478711]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	3050.0	n.a.	PMID[16792410]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	767.0	n.a.	PMID[18380425]
NPT2	Others	Unspecified	n.a.	Ratio Ki	=	700.0	n.a.	PMID[18380425]
NPT2	Others	Unspecified	n.a.	Ratio Ki	>	530.0	n.a.	PMID[16792410]
NPT2	Others	Unspecified	n.a.	Ratio Ki	>	10000.0	n.a.	PMID[21115248]
NPT2	Others	Unspecified	n.a.	Ratio Ki	>	1351.0	n.a.	PMID[21338114]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	ED50	=	0.59	mg.kg-1	PMID[16033256]
NPT32	Organism	Mus musculus	Mus musculus	ED50	=	1.98	mg.kg-1	PMID[16033256]
NPT32	Organism	Mus musculus	Mus musculus	Inhibition	=	28.0	%	PMID[16033256]
NPT32	Organism	Mus musculus	Mus musculus	ED50	=	1.285	mg.kg-1	PMID[28376298]
NPT32	Organism	Mus musculus	Mus musculus	Emax	=	100.0	%	PMID[28376298]
NPT32	Organism	Mus musculus	Mus musculus	ED50	=	1.5	ug	PMID[34995453]
NPT32	Organism	Mus musculus	Mus musculus	ED50	=	2.1	mg.kg-1	PMID[34995453]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	EC50	=	46.0	nM	PMID[15658846]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Emax	=	100.0	%	PMID[15658846]

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference
Canis lupus familiaris	n.a.	permeability	=	54.2	%	PMID[25075762]
Canis lupus familiaris	n.a.	permeability	=	21.2	%	PMID[25075762]

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 NPC262198 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	13364
0.1-0.2	35058
0.2-0.3	1153
0.3-0.4	232
0.4-0.5	33
0.5-0.6	9
0.6-0.7	5
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	Natural Product ID
1.0	High Similarity	NPC485313
0.75	Intermediate Similarity	NPC485320
0.6765	Remote Similarity	NPC601789
0.6623	Remote Similarity	NPC485321
0.6538	Remote Similarity	NPC485322
0.6301	Remote Similarity	NPC485323
0.6027	Remote Similarity	NPC485324
0.5797	Remote Similarity	NPC476943
0.5641	Remote Similarity	NPC606944
0.5584	Remote Similarity	NPC610593
0.5443	Remote Similarity	NPC610061
0.5333	Remote Similarity	NPC310830
0.5325	Remote Similarity	NPC18347
0.527	Remote Similarity	NPC608381
0.527	Remote Similarity	NPC609872
0.5205	Remote Similarity	NPC606229

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC262198 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3824
0.1-0.2	5274
0.2-0.3	52
0.3-0.4	0
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