NPASS Compound

Natural Product: NPC35390

Natural Product ID	NPC35390
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Methyllycaconitine
IUPAC Name	n.a.
Synonyms	Methyllycaconitine; Methyllycanonitine
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL510275
PubChem CID	44575473
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0003788] Aconitane-type diterpenoid alkaloids

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 2D 99106 0 0 0 0 0 0 0 0999 V2000 -4.8476 -0.3425 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3498 -0.4244 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2313 -0.9596 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.0796 -1.0061 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7062 -2.6807 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4086 -3.6844 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8351 -3.2209 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1470 -1.7537 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 -0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8578 2.6401 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2760 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 -1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3907 1.0037 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8173 0.5402 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8192 2.0952 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1895 1.4851 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3463 -0.0067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8136 -0.3186 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5636 0.9805 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5599 2.0952 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7734 2.9769 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6166 4.4687 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3463 2.6982 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9087 3.1262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5182 4.1884 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8946 4.7846 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6624 3.5870 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9419 -0.4816 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4410 -0.5340 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1328 -3.1443 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5593 -3.6078 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8712 -5.0750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7565 -6.0787 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2978 -5.5385 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6097 -7.0058 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0362 -7.4693 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1510 -6.4656 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8391 -4.9984 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4125 -4.5348 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1006 -3.0676 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.7303 -2.4575 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2884 -2.8709 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8871 -0.9657 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3543 -0.6539 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1043 -1.9529 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5961 -2.1097 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8908 0.7727 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3242 -0.0787 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3080 1.0851 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1114 -1.8191 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2680 1.0734 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7916 -1.8578 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6095 -2.2796 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3602 -3.3326 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1128 -5.0089 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6521 -4.7451 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3342 -3.2733 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0439 -4.7063 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2440 -2.7768 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4231 1.3118 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3250 2.9520 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6004 -0.7041 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8615 -1.5254 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2439 0.0766 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2808 1.9668 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1833 -0.8193 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3724 2.9739 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8347 -1.4249 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8922 -1.8165 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3115 -0.3969 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0553 1.1373 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9738 3.4760 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2791 5.9302 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1164 4.4424 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1677 4.8570 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8216 2.9696 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9562 4.2850 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4113 4.5395 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1881 5.5442 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4706 6.2234 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9446 3.7134 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7079 4.1971 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8828 -0.9475 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6757 0.9476 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3886 -2.0331 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8466 -4.6167 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9277 -1.8722 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4949 -8.0095 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3481 -8.9365 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5775 -6.9291 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9538 -3.9947 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3983 -1.1486 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7303 0.5260 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7247 -0.0438 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4273 2.1993 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3174 1.2362 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6188 -0.0222 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 9 8 1 6 9 10 1 0 10 11 1 0 11 12 1 1 11 13 1 0 13 14 1 0 13 15 1 0 15 16 1 0 11 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 21 25 1 0 25 26 1 0 25 27 1 0 27 28 1 0 17 29 1 1 8 30 1 0 30 31 1 0 5 32 1 6 32 33 1 0 33 34 1 0 34 35 2 0 34 36 1 0 36 37 2 0 37 38 1 0 38 39 2 0 39 40 1 0 40 41 2 0 41 42 1 0 42 43 1 0 43 44 2 0 43 45 1 0 45 46 1 0 46 47 1 0 47 48 2 0 46 49 1 0 10 3 1 0 26 17 1 0 41 36 1 0 47 42 1 0 14 5 1 0 22 18 1 0 14 9 1 0 19 9 1 0 1 50 1 0 1 51 1 0 1 52 1 0 2 53 1 0 2 54 1 0 4 55 1 0 4 56 1 0 6 57 1 0 6 58 1 0 7 59 1 0 7 60 1 0 8 61 1 1 10 62 1 6 12 63 1 0 13 64 1 6 14 65 1 1 16 66 1 0 16 67 1 0 16 68 1 0 18 69 1 1 19 70 1 1 20 71 1 0 20 72 1 0 21 73 1 1 22 74 1 1 24 75 1 0 24 76 1 0 24 77 1 0 25 78 1 6 26 79 1 0 26 80 1 0 28 81 1 0 28 82 1 0 28 83 1 0 29 84 1 0 31 85 1 0 31 86 1 0 31 87 1 0 32 88 1 0 32 89 1 0 37 90 1 0 38 91 1 0 39 92 1 0 40 93 1 0 45 94 1 0 45 95 1 0 46 96 1 1 49 97 1 0 49 98 1 0 49 99 1 0 M END

Standard InCHIKey	XLTANAWLDBYGFU-BVFBBISOSA-N
Standard InCHI	InChI=1S/C37H50N2O10/c1-7-38-17-34(18-49-32(42)20-10-8-9-11-23(20)39-26(40)14-19(2)31(39)41)13-12-25(46-4)36-22-15-21-24(45-3)16-35(43,27(22)28(21)47-5)37(44,33(36)38)30(48-6)29(34)36/h8-11,19,21-22,24-25,27-30,33,43-44H,7,12-18H2,1-6H3/t19-,21+,22+,24-,25-,27+,28-,29+,30-,33-,34-,35+,36-,37-/m0/s1
SMILES	CCN1C[C@@]2(CC[C@@H]([C@]34[C@H]1[C@@](O)([C@H]([C@H]23)OC)[C@@]1([C@@H]2[C@H]4C[C@@H]([C@@H]2OC)[C@H](C1)OC)O)OC)COC(=O)c1ccccc1N1C(=O)C[C@@H](C1=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	682.35	Volume:	674.133 ? Van der Waals volume.
Dense:	1.012	LogP:	1.846 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.16 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.324 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	38.0
TPSA:	144.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	2.0	Rings:	8.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.292	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.255	Fsp³:	0.757
MCE-18:	244.615 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.478	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.01 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.006 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.649

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.374	MDCK Permeability:	-5.146
Pgp-inhibitor:	0.0	Pgp-substrate:	0.26
PAMPA:	0.977 ? 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%):	0.014	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.058

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.035	MRP1:	0.996
Plasma Protein Binding (PPB):	81.91%	Volume Distribution (VD):	0.166
Fu:	21.048% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.607
OATP1B3 inhibitor:	0.416	BCRP inhibitor:	0.0
BSEP inhibitor:	0.661

ADMET: Metabolism

CYP1A2-inhibitor:	0.925	CYP1A2-substrate:	0.352
CYP2C19-inhibitor:	0.967	CYP2C19-substrate:	0.535
CYP2C9-inhibitor:	0.05	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.642
CYP3A4-inhibitor:	0.407	CYP3A4-substrate:	0.026
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.294
HLM stability:	0.989 ? 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):

3.69

Half-life (T1/2):

2.017

ADMET: Toxicity

hERG Blockers:	0.062	hERG Blockers (10um):	0.299
Human Hepatotoxicity (H-HT):	0.259	Drug-induced Liver Injury (DILI):	0.899
AMES Toxicity:	0.664	Rat Oral Acute Toxicity:	0.262
Maximum Recommended Daily Dose:	0.245	Skin Sensitization:	0.998
Carcinogencity:	0.721	Eye Corrosion:	0.0
Eye Irritation:	0.053	Respiratory Toxicity:	0.771
Drug-induced Neurotoxicity:	0.895	Ototoxicity:	0.733
Hematotoxicity:	0.838	Drug-induced Nephrotoxicity:	0.927
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.07
A549 Cytotoxicity:	0.192	Hek293 Cytotoxicity:	0.769
BCF:	0.76 ? 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:	3.885 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.051 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.782 ? 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
NPO32441	delphinium sp.	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9748371]
NPO32441	delphinium sp.	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
Blockage	1
Ki	51
IC50	18
Inhibition	1
Concentration	2
Activity	3
EC50	1
Ratio	3
AD50	2

Activity Type	# Activity
Individual protein	27
Protein complex	13
Organism	3
Others	39

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT416	Protein complex	Neuronal acetylcholine receptor; alpha3/beta2	Rattus norvegicus	Ki	=	2.3	nM	PMID[19743809]
NPT1783	Protein complex	Serotonin 3 (5-HT3) receptor	Homo sapiens	Ki	=	16.5	%	PubChem BioAssay data set
NPT412	Protein complex	Neuronal acetylcholine receptor; alpha4/beta2	Rattus norvegicus	Ki	=	1560.0	nM	PMID[14640526]
NPT412	Protein complex	Neuronal acetylcholine receptor; alpha4/beta2	Rattus norvegicus	Ki	=	1460.0	nM	PMID[21440449]
NPT6604	Individual protein	Neuronal acetylcholine receptor protein alpha-10 subunit	Rattus norvegicus	Ki	=	1300.0	nM	PMID[20158243]
NPT409	Protein complex	Neuronal acetylcholine receptor; alpha4/beta2	Homo sapiens	Concentration	>	1.0	%	PMID[16033252]
NPT3921	Protein complex	Neuronal acetylcholine receptor; alpha2/beta4	Homo sapiens	IC50	>	1000.0	nM	DOI[10.6019/CHEMBL1201861]
NPT3920	Protein complex	Neuronal acetylcholine receptor; alpha4/beta4	Homo sapiens	Concentration	>	1.0	uM	PMID[16033252]
NPT409	Protein complex	Neuronal acetylcholine receptor; alpha4/beta2	Homo sapiens	Ki	>	10000.0	nM	PMID[16643041]
NPT412	Protein complex	Neuronal acetylcholine receptor; alpha4/beta2	Rattus norvegicus	Ki	=	400.0	nM	PMID[8759171]
NPT410	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Homo sapiens	Blockage	=	100.0	%	PMID[15050620]
NPT6298	Protein complex	Chromaffin cell neuronal nicotinic acetylcholine receptor	Bos taurus	Inhibition	=	95.2	%	PMID[22801644]
NPT410	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Homo sapiens	IC50	>	1000.0	nM	DOI[10.6019/CHEMBL1201861]
NPT410	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Homo sapiens	Ki	=	7.3	nM	PubChem BioAssay data set
NPT410	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Homo sapiens	Ki	=	1.1	nM	DrugMatrix in vivo data: Pathology
NPT410	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Homo sapiens	Ki	=	1.0	nM	DrugMatrix in vivo data: Pathology
NPT410	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Homo sapiens	Ki	=	6.1	nM	PMID[11575949]
NPT410	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Homo sapiens	Ki	=	6.31	nM	PMID[19344127]
NPT410	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Homo sapiens	Ki	=	1.6	nM	PMID[17722904]
NPT410	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Homo sapiens	Ki	=	1.622	nM	PMID[17722904]
NPT410	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Homo sapiens	IC50	=	8.3	nM	PMID[8176404]
NPT410	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Homo sapiens	IC50	=	8.318	nM	PubChem BioAssay data set
NPT6362	Individual protein	Neuronal acetylcholine receptor subunit alpha-3	Bos taurus	Activity	=	50.1	%	PMID[19738026]
NPT414	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Rattus norvegicus	Ki	=	1560.0	nM	PMID[22925447]
NPT414	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Rattus norvegicus	Ki	=	0.8	nM	PMID[20045651]
NPT414	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Rattus norvegicus	Ki	=	0.6	nM	PMID[20045651]
NPT414	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Rattus norvegicus	Ki	>	1000.0	nM	PMID[20045651]
NPT414	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Rattus norvegicus	Ki	=	2.3	nM	PMID[16643041]
NPT414	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Rattus norvegicus	Ki	=	4.8	nM	PMID[17896816]
NPT414	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Rattus norvegicus	IC50	=	7.6	nM	PMID[19128055]
NPT411	Protein complex	Neuronal acetylcholine receptor; alpha3/beta4	Homo sapiens	IC50	=	2600.0	nM	PMID[18052325]
NPT423	Protein complex	Neuronal acetylcholine receptor; alpha3/beta2	Homo sapiens	IC50	>	1000.0	nM	PMID[21856049]
NPT411	Protein complex	Neuronal acetylcholine receptor; alpha3/beta4	Homo sapiens	IC50	>	1000.0	nM	DOI[10.6019/CHEMBL1201861]
NPT414	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Rattus norvegicus	Ki	=	0.87	nM	PMID[12713403]
NPT6221	Individual protein	Neuronal acetylcholine receptor subunit alpha-7	Bos taurus	Activity	=	7.5	%	PMID[11087617]
NPT414	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Rattus norvegicus	Ki	=	4.0	nM	PMID[17336534]
NPT414	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Rattus norvegicus	Ki	=	2.91	nM	PMID[17279798]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	Ki	=	739.0	nM	PMID[25679337]
NPT2	Others	Unspecified	n.a.	Ki	=	24.0	nM	DrugMatrix in vitro pharmacology data
NPT2	Others	Unspecified	n.a.	Ki	=	23.99	nM	DrugMatrix in vitro pharmacology data
NPT2	Others	Unspecified	n.a.	Ki	=	4.5	nM	PMID[15771411]
NPT2	Others	Unspecified	n.a.	Ki	=	4.467	nM	PMID[20060625]
NPT2	Others	Unspecified	n.a.	Ki	=	3.5	nM	PMID[16792420]
NPT2	Others	Unspecified	n.a.	Ki	=	3.548	nM	PMID[16792420]
NPT2	Others	Unspecified	n.a.	Ki	=	3.2	nM	PMID[11063609]
NPT2	Others	Unspecified	n.a.	Ki	=	3.802	nM	PMID[21377877]
NPT2	Others	Unspecified	n.a.	Ki	=	3.9	nM	Open TG-GATES in vivo data: Hematology
NPT2	Others	Unspecified	n.a.	Ki	=	3.89	nM	Open TG-GATES in vivo data: Hematology
NPT2	Others	Unspecified	n.a.	Ki	=	4.3	nM	PMID[16506833]
NPT2	Others	Unspecified	n.a.	Ki	=	4.266	nM	PMID[16506833]
NPT2	Others	Unspecified	n.a.	Ki	=	2.5	nM	PMID[21612217]
NPT2	Others	Unspecified	n.a.	Ki	=	2.512	nM	PMID[21612217]
NPT2	Others	Unspecified	n.a.	Ki	=	1.9	nM	PMID[20478710]
NPT2	Others	Unspecified	n.a.	Ki	=	1.95	nM	PMID[20478710]
NPT2	Others	Unspecified	n.a.	Ki	=	13.0	nM	PMID[11374943]
NPT2	Others	Unspecified	n.a.	Ki	=	12.88	nM	PMID[11374943]
NPT2	Others	Unspecified	n.a.	Ki	=	1.7	nM	DOI[10.6019/CHEMBL1201861]
NPT2	Others	Unspecified	n.a.	Ki	=	1.66	nM	PMID[16499324]
NPT2	Others	Unspecified	n.a.	Ki	=	5.5	nM	PMID[23734721]
NPT2	Others	Unspecified	n.a.	Ki	=	5.495	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	IC50	=	10000.0	nM	PMID[8864236]
NPT2	Others	Unspecified	n.a.	IC50	=	31622.78	nM	PMID[25066952]
NPT2	Others	Unspecified	n.a.	IC50	=	89.0	nM	PMID[23046382]
NPT2	Others	Unspecified	n.a.	IC50	=	1800.0	nM	Open TG-GATES in vivo data: Biochemistry
NPT2	Others	Unspecified	n.a.	IC50	=	1819.7	nM	PMID[22295903]
NPT2	Others	Unspecified	n.a.	IC50	=	320.0	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	IC50	=	323.59	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	EC50	=	29512.09	nM	PMID[15646539]
NPT2	Others	Unspecified	n.a.	Ratio	=	100.0	n.a.	PMID[11374943]
NPT2	Others	Unspecified	n.a.	Ratio	=	1000.0	n.a.	PMID[11374943]
NPT2	Others	Unspecified	n.a.	Ratio	=	10000.0	n.a.	PMID[11374943]
NPT2	Others	Unspecified	n.a.	Ki	=	0.37	nM	PMID[18183025]
NPT2	Others	Unspecified	n.a.	Ki	=	0.15	nM	DOI[10.1016/S0960-894X(97)10055-5]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	AD50	=	2.0	mg kg-1	PMID[18355033]
NPT32	Organism	Mus musculus	Mus musculus	AD50	=	12.0	mg kg-1	PMID[18355033]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	15.0	%	PMID[24766560]

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
-	Mus musculus	LD50	=	7.5	mg.kg-1	PMID[24175613]
-	Mus musculus	LD50	=	3.0	mg.kg-1	PMID[17336534]

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 NPC35390 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	14332
0.1-0.2	34815
0.2-0.3	647
0.3-0.4	38
0.4-0.5	10
0.5-0.6	4
0.6-0.7	3
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	3
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC611189
0.9333	High Similarity	NPC470631
0.9333	High Similarity	NPC481816
0.9022	High Similarity	NPC481815
0.8876	High Similarity	NPC473781
0.8021	Intermediate Similarity	NPC475316
0.7812	Intermediate Similarity	NPC473486
0.75	Intermediate Similarity	NPC481814
0.7158	Intermediate Similarity	NPC223590
0.6415	Remote Similarity	NPC473667
0.6239	Remote Similarity	NPC106593
0.6087	Remote Similarity	NPC476501
0.5543	Remote Similarity	NPC474210
0.5435	Remote Similarity	NPC96080
0.5435	Remote Similarity	NPC99905
0.5435	Remote Similarity	NPC208118

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC35390 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3327
0.1-0.2	5785
0.2-0.3	37
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