NPASS Compound

Natural Product: NPC473781

Natural Product ID	NPC473781
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Lycaconitine
IUPAC Name	n.a.
Synonyms	Lycaconitine
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL451640
PubChem CID	441745
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 3D 96103 0 0 0 0 0 0 0 0999 V2000 -0.4636 2.6341 2.4009 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1587 1.5502 1.9728 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7860 0.9847 0.7947 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5181 -0.5002 0.8519 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7732 -0.6727 0.0566 C 0 0 1 0 0 0 0 0 0 0 0 0 1.1182 -2.1246 -0.1921 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0144 -2.6703 -1.0617 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3060 -2.5060 -0.3265 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6411 -1.1259 0.0505 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7524 -0.1109 -1.0453 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8811 1.1800 -0.2320 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6914 2.3029 -1.0148 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1888 1.2779 0.5214 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0373 2.4160 1.3585 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3228 1.6089 -0.3871 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2474 0.4879 -0.6998 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.2762 -0.6021 0.3121 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1254 -1.5722 -0.0031 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9503 -1.1735 0.7862 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.3666 0.1142 1.4194 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.8765 -0.0698 1.6437 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.4943 1.1268 1.9484 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1678 0.9408 3.1685 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5725 0.9693 -0.8162 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1203 0.7141 -2.0487 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6114 0.0328 -1.8511 N 0 0 0 0 0 0 0 0 0 0 0 0 0.6559 -0.0009 -1.2860 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7744 0.2650 -3.2244 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4852 0.4061 -4.0118 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2069 -3.2386 -1.0311 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5013 -4.4359 -0.3838 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9643 -0.1180 0.8148 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0961 -0.3392 -0.0273 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3784 0.0387 0.3318 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5594 0.5917 1.4268 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4941 -0.2152 -0.5735 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2629 -0.8370 -1.7962 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2971 -1.0844 -2.6610 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5752 -0.7132 -2.3138 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7959 -0.1058 -1.1177 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7673 0.1638 -0.2084 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0395 0.8020 1.0351 N 0 0 0 0 0 0 0 0 0 0 0 0 7.3636 0.1758 2.2575 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3561 -1.0712 2.4670 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7241 1.1698 3.2989 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8143 2.4617 2.5550 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0423 2.2083 1.3082 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4896 3.0948 0.6196 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6120 2.3576 2.5380 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8245 2.8986 3.4218 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5764 3.5533 1.7945 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0742 1.5858 0.4131 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4143 -0.9003 1.8575 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0453 -2.1224 -0.7937 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2353 -2.7204 0.7095 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0043 -2.2832 -2.0894 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1839 -3.7635 -1.1354 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1039 -3.0699 0.6389 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6413 -0.2149 -1.6711 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9590 2.8546 -0.6301 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0403 3.2414 0.8025 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9329 2.4819 -0.0490 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8725 1.9505 -1.3632 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0230 0.0184 -1.6918 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2596 -1.1288 0.3298 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0285 -1.5887 -1.0818 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5452 -2.5748 0.2979 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8149 -1.9208 1.6205 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9589 0.1796 2.4291 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0516 -0.8573 2.4014 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6914 1.8635 3.4812 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9092 0.1048 3.0941 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3737 0.6501 3.8985 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1491 1.1257 -2.0402 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5832 1.2675 -2.8594 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2097 -0.3643 -2.2838 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3546 -0.5499 -1.9854 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0989 1.0194 -1.2389 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4527 1.1317 -3.3745 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3351 -0.6102 -3.6682 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0570 -0.5302 -4.0034 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0719 1.3043 -3.7500 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1796 0.5617 -5.0883 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9213 -4.2695 0.6261 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5596 -5.0154 -0.2270 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2571 -5.0332 -0.9362 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1130 -0.7899 1.7028 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8759 0.9271 1.0923 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2464 -1.1260 -2.0594 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1397 -1.5665 -3.6164 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4280 -0.8874 -2.9647 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7883 0.1964 -0.8189 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7274 0.9377 3.7186 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9531 1.2525 4.0951 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8681 2.6860 2.2259 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4035 3.3068 3.1440 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 8 9 1 0 9 10 1 6 10 11 1 0 11 12 1 6 11 13 1 0 13 14 1 1 13 15 1 0 15 16 1 0 16 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 16 24 1 0 24 25 1 0 10 26 1 0 26 27 1 0 26 28 1 0 28 29 1 0 8 30 1 0 30 31 1 0 5 32 1 1 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 11 3 1 0 20 13 1 0 41 36 1 0 47 42 1 0 9 4 1 0 21 17 1 0 27 5 1 0 19 9 1 0 1 49 1 0 1 50 1 0 1 51 1 0 3 52 1 6 4 53 1 1 6 54 1 0 6 55 1 0 7 56 1 0 7 57 1 0 8 58 1 1 10 59 1 0 12 60 1 0 14 61 1 0 15 62 1 0 15 63 1 0 16 64 1 6 17 65 1 1 18 66 1 0 18 67 1 0 19 68 1 1 20 69 1 1 21 70 1 1 23 71 1 0 23 72 1 0 23 73 1 0 25 74 1 0 25 75 1 0 25 76 1 0 27 77 1 0 27 78 1 0 28 79 1 0 28 80 1 0 29 81 1 0 29 82 1 0 29 83 1 0 31 84 1 0 31 85 1 0 31 86 1 0 32 87 1 0 32 88 1 0 37 89 1 0 38 90 1 0 39 91 1 0 40 92 1 0 45 93 1 0 45 94 1 0 46 95 1 0 46 96 1 0 M END

Standard InCHIKey	KFXVNXQXPRPLQA-CPIHIRBUSA-N
Standard InCHI	InChI=1S/C36H48N2O10/c1-6-37-17-33(18-48-31(41)19-9-7-8-10-22(19)38-25(39)11-12-26(38)40)14-13-24(45-3)35-21-15-20-23(44-2)16-34(42,27(21)28(20)46-4)36(43,32(35)37)30(47-5)29(33)35/h7-10,20-21,23-24,27-30,32,42-43H,6,11-18H2,1-5H3/t20-,21-,23+,24+,27-,28+,29-,30+,32?,33+,34-,35+,36-/m1/s1
SMILES	CO[C@H]1[C@@H]2[C@]3(CC[C@@H]([C@@]42C([C@@]1(O)[C@@]1(O)C[C@@H]([C@H]2C[C@@H]4[C@@H]1[C@H]2OC)OC)N(C3)CC)OC)COC(=O)c1ccccc1N1C(=O)CCC1=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	668.33	Volume:	656.837 ? Van der Waals volume.
Dense:	1.017	LogP:	1.363 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.815 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.444 ? 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:	0.294	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.159	Fsp³:	0.75
MCE-18:	241.016 ? 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:	0.373	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.02 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.015 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.378

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.271	MDCK Permeability:	-5.029
Pgp-inhibitor:	0.0	Pgp-substrate:	0.0
PAMPA:	0.816 ? 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%):	0.013	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.219

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.378	MRP1:	0.549
Plasma Protein Binding (PPB):	73.674%	Volume Distribution (VD):	0.179
Fu:	29.917% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.914
OATP1B3 inhibitor:	0.626	BCRP inhibitor:	0.0
BSEP inhibitor:	0.753

ADMET: Metabolism

CYP1A2-inhibitor:	0.802	CYP1A2-substrate:	0.006
CYP2C19-inhibitor:	0.429	CYP2C19-substrate:	0.079
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.074
CYP3A4-inhibitor:	0.949	CYP3A4-substrate:	0.139
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.048
HLM stability:	0.99 ? 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):

4.736

Half-life (T1/2):

2.083

ADMET: Toxicity

hERG Blockers:	0.08	hERG Blockers (10um):	0.331
Human Hepatotoxicity (H-HT):	0.207	Drug-induced Liver Injury (DILI):	0.205
AMES Toxicity:	0.591	Rat Oral Acute Toxicity:	0.235
Maximum Recommended Daily Dose:	0.261	Skin Sensitization:	0.919
Carcinogencity:	0.679	Eye Corrosion:	0.0
Eye Irritation:	0.029	Respiratory Toxicity:	0.385
Drug-induced Neurotoxicity:	0.708	Ototoxicity:	0.717
Hematotoxicity:	0.444	Drug-induced Nephrotoxicity:	0.643
Genotoxicity:	0.974	RPMI-8226 Immunitoxicity:	0.077
A549 Cytotoxicity:	0.071	Hek293 Cytotoxicity:	0.72
BCF:	0.442 ? 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:	3.443 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.118 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.399 ? 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
NPO33014	delphinium cashmirianum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[541686]

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	2
Activity	7
EC50	1

Activity Type	# Activity
Individual protein	1
Organism	7
Protein complex	1
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT412	Protein complex	Neuronal acetylcholine receptor; alpha4/beta2	Rattus norvegicus	Ki	=	1000.0	nM	PMID[8759171]
NPT414	Individual protein	Neuronal acetylcholine receptor protein alpha-7 subunit	Rattus norvegicus	Ki	=	80.0	nM	PMID[16124770]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT419	Organism	Oryctolagus cuniculus	Oryctolagus cuniculus	Activity	=	-10.0	bpm	PMID[20726569]
NPT419	Organism	Oryctolagus cuniculus	Oryctolagus cuniculus	Activity	=	0.0	bpm	PMID[20726569]
NPT419	Organism	Oryctolagus cuniculus	Oryctolagus cuniculus	Activity	=	3.0	bpm	PMID[20726569]
NPT419	Organism	Oryctolagus cuniculus	Oryctolagus cuniculus	Activity	=	5.0	bpm	PubChem BioAssay data set
NPT419	Organism	Oryctolagus cuniculus	Oryctolagus cuniculus	Activity	=	-5.0	bpm	PMID[20726569]
NPT2	Others	Unspecified	n.a.	EC50	=	14791.08	nM	PMID[15646539]

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
-	Mus musculus	LD50	=	15.0	mg.kg-1	PMID[24461297]

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 NPC473781 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	13724
0.1-0.2	35380
0.2-0.3	688
0.3-0.4	40
0.4-0.5	10
0.5-0.6	4
0.6-0.7	5
0.7-0.8	0
0.8-0.85	3
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8876	High Similarity	NPC35390
0.8876	High Similarity	NPC611189
0.8298	Intermediate Similarity	NPC470631
0.8298	Intermediate Similarity	NPC481816
0.8021	Intermediate Similarity	NPC481815
0.7312	Intermediate Similarity	NPC223590
0.71	Intermediate Similarity	NPC475316
0.69	Remote Similarity	NPC473486
0.6635	Remote Similarity	NPC481814
0.6538	Remote Similarity	NPC473667
0.6355	Remote Similarity	NPC106593
0.6222	Remote Similarity	NPC476501
0.5667	Remote Similarity	NPC474210
0.5556	Remote Similarity	NPC96080
0.5556	Remote Similarity	NPC99905
0.5556	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 NPC473781 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3204
0.1-0.2	5883
0.2-0.3	62
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