NPASS Compound

Natural Product: NPC476397

Natural Product ID	NPC476397
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Artemether Complex
IUPAC Name	[(2R,3R,4S,5R,6R)-4-[(2S,3R,4R,5R,6S)-4,5-dihydroxy-6-methyl-3-[(2S,3R,4R,5S)-3,4,5-trihydroxyoxan-2-yl]oxyoxan-2-yl]oxy-6-[2-(3,4-dihydroxyphenyl)ethoxy]-3,5-dihydroxyoxan-2-yl]methyl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL595333
PubChem CID	46227139
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0000198] Oligosaccharides

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 97101 0 0 0 0 0 0 0 0999 V2000 -3.4696 -0.0298 -3.7114 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7193 -0.6595 -2.3314 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8510 -1.8607 -2.2351 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6024 -2.3843 -0.8707 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6364 -1.3107 0.1751 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4622 0.0168 -0.5109 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4800 0.3137 -1.4069 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2183 0.1373 -1.1170 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4234 1.1400 -0.5621 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7679 0.5168 0.0642 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0764 1.1867 -0.1837 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8567 2.5369 -0.2971 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1434 2.9156 -1.4243 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1552 2.1990 -1.5836 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2228 1.6385 -2.8574 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9567 4.2980 -1.3081 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6469 5.0015 -2.2906 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3534 6.4798 -2.0261 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8305 6.8506 -0.6564 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0205 6.7454 0.4395 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4811 7.0910 1.6965 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7882 7.5549 1.8618 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5943 7.6567 0.7517 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1191 7.3052 -0.5121 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2399 7.8997 3.1348 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6951 6.9989 2.8261 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8265 0.6084 -1.3583 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0491 -0.7743 -1.2302 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7752 -1.3522 -0.2216 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2920 -0.6284 0.6618 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9803 -2.8061 -0.1255 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6827 -3.3116 0.8564 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9191 -4.7342 1.0043 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6756 -5.2339 2.0639 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9173 -6.5700 2.2336 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3978 -7.4711 1.3272 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6495 -6.9976 0.2758 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4134 -5.6418 0.1174 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6316 -8.8487 1.4792 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6769 -7.0123 3.3062 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9066 -0.8373 -0.3250 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9097 -1.3247 0.7392 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9320 -1.4812 2.1008 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7723 -2.6767 2.5224 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1978 -2.4620 2.1328 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4619 -1.2166 1.3504 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6144 -0.0465 1.7328 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6016 -0.3570 2.6384 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4224 -1.4616 -0.0402 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6283 -3.5554 1.3780 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6751 -2.7287 3.9307 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2968 -2.9309 -0.8556 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6900 -1.6494 -2.9784 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3775 -0.1019 -3.9003 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8330 1.0160 -3.7394 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9816 -0.6499 -4.4460 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8066 -0.9641 -2.3723 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3934 -2.6851 -2.7924 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2552 -3.2504 -0.6153 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8409 -1.4254 0.9383 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5015 0.7854 0.3205 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0495 1.5859 0.2684 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6373 0.4415 1.1854 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7251 1.0535 0.7197 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8101 2.7641 -2.2972 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9754 2.9473 -1.5353 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4048 2.0523 -3.4881 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2497 4.7328 -3.2733 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7397 4.8444 -2.2064 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8478 7.0767 -2.8060 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2669 6.6716 -2.0421 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0084 6.3869 0.3153 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6073 8.0138 0.8621 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7433 7.3827 -1.3794 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2070 8.1829 3.2245 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8120 7.6295 3.5849 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3340 0.7982 -2.3306 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8348 1.0859 -1.3523 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5290 -3.4042 -0.8905 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1131 -2.6264 1.6030 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0658 -4.4985 2.7522 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2550 -7.7292 -0.4195 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8239 -5.3644 -0.7249 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0910 -9.3611 0.7375 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2848 -7.5821 4.0292 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6891 -0.8791 -1.2736 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9228 -1.5741 2.5237 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3443 -3.6231 2.1519 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8502 -2.4415 3.0503 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5331 -0.9120 1.5422 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1981 0.7970 2.1561 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1303 0.3438 0.8016 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1592 -2.0721 -0.2261 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1945 -4.3970 1.6594 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4056 -2.1325 4.2775 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2059 -3.3101 0.0643 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0420 -2.3445 -2.6850 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 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 13 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 22 25 1 0 21 26 1 0 11 27 1 0 27 28 1 0 28 29 1 0 29 30 2 0 29 31 1 0 31 32 2 3 32 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 36 37 1 0 37 38 2 0 36 39 1 0 35 40 1 0 10 41 1 0 5 42 1 0 42 43 1 0 43 44 1 0 44 45 1 0 45 46 1 0 46 47 1 0 47 48 1 0 46 49 1 0 45 50 1 0 44 51 1 0 4 52 1 0 3 53 1 0 7 2 1 0 14 9 1 0 24 19 1 0 38 33 1 0 48 43 1 0 1 54 1 0 1 55 1 0 1 56 1 0 2 57 1 0 3 58 1 0 4 59 1 0 5 60 1 0 6 61 1 0 9 62 1 0 10 63 1 0 11 64 1 0 13 65 1 0 14 66 1 0 15 67 1 0 17 68 1 0 17 69 1 0 18 70 1 0 18 71 1 0 20 72 1 0 23 73 1 0 24 74 1 0 25 75 1 0 26 76 1 0 27 77 1 0 27 78 1 0 31 79 1 0 32 80 1 0 34 81 1 0 37 82 1 0 38 83 1 0 39 84 1 0 40 85 1 0 41 86 1 0 43 87 1 0 44 88 1 0 45 89 1 0 46 90 1 0 47 91 1 0 47 92 1 0 49 93 1 0 50 94 1 0 51 95 1 0 52 96 1 0 53 97 1 0 M END

Standard InCHIKey	QBKQKZMPUZQDGD-ZQBVNWIYSA-N
Standard InCHI	InChI=1S/C34H44O19/c1-14-24(41)27(44)31(53-32-28(45)25(42)21(39)12-49-32)34(50-14)52-30-26(43)22(13-48-23(40)7-4-15-2-5-17(35)19(37)10-15)51-33(29(30)46)47-9-8-16-3-6-18(36)20(38)11-16/h2-7,10-11,14,21-22,24-39,41-46H,8-9,12-13H2,1H3/b7-4+/t14-,21-,22+,24-,25+,26+,27+,28+,29+,30-,31+,32-,33+,34-/m0/s1
SMILES	CC1C(C(C(C(O1)OC2C(C(OC(C2O)OCCC3=CC(=C(C=C3)O)O)COC(=O)C=CC4=CC(=C(C=C4)O)O)O)OC5C(C(C(CO5)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	756.25	Volume:	699.76 ? Van der Waals volume.
Dense:	1.081	LogP:	-0.965 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.059 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.171 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	13.0	Rigid Bonds:	32.0
TPSA:	304.21 ? Topological Polar Surface Area.	H-Bond Acceptor:	19.0
H-Bond Donor:	11.0	Rings:	5.0
Heavy Atoms:	19.0

MedChem Properties

QED Drug-Likeness Score:	0.06	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.303	Fsp³:	0.559
MCE-18:	128.377 ? 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:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.35	Fluc inhibitor:	0.582 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.101 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.909 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.406	Promiscuous compounds:	0.632

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.327	MDCK Permeability:	-5.144
Pgp-inhibitor:	0.0	Pgp-substrate:	0.949
PAMPA:	1.0 ? 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):	1.0
20% Bioavailability (F20%):	1.0	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.825
Plasma Protein Binding (PPB):	53.76%	Volume Distribution (VD):	-0.461
Fu:	40.035% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.004
OATP1B3 inhibitor:	0.976	BCRP inhibitor:	0.011
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.008
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.005 ? 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):

1.248

Half-life (T1/2):

4.187

ADMET: Toxicity

hERG Blockers:	0.061	hERG Blockers (10um):	0.806
Human Hepatotoxicity (H-HT):	0.27	Drug-induced Liver Injury (DILI):	0.465
AMES Toxicity:	0.888	Rat Oral Acute Toxicity:	0.142
Maximum Recommended Daily Dose:	0.49	Skin Sensitization:	0.995
Carcinogencity:	0.01	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.002
Drug-induced Neurotoxicity:	0.026	Ototoxicity:	0.999
Hematotoxicity:	0.002	Drug-induced Nephrotoxicity:	0.022
Genotoxicity:	0.448	RPMI-8226 Immunitoxicity:	0.027
A549 Cytotoxicity:	0.871	Hek293 Cytotoxicity:	0.858
BCF:	0.491 ? 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:	3.117 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.138 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.167 ? 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
NPO33377	teucrium chamaedris	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19674906]

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
Activity	4
IC50	4
Fapp	2

Activity Type	# Activity
Others	2
Non-molecular	6
Organism	2

Molecular-level activity

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

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	0.7	n.a.	PMID[19674906]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	1.2	n.a.	PMID[19674906]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	1.8	n.a.	PMID[19674906]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	26300.0	nM	PMID[19674906]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	33500.0	nM	PMID[19674906]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	38000.0	nM	PMID[19674906]
NPT1	Others	Radical scavenging activity	n.a.	Activity	=	0.5	n.a.	PMID[20801038]
NPT1	Others	Radical scavenging activity	n.a.	IC50	=	38300.0	nM	PMID[8691203]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Fapp	=	100.0	%	PMID[19665897]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Fapp	=	181.0	%	PMID[19665897]

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 NPC476397 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	17277
0.1-0.2	28911
0.2-0.3	3153
0.3-0.4	392
0.4-0.5	77
0.5-0.6	28
0.6-0.7	11
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8556	High Similarity	NPC476398
0.7738	Intermediate Similarity	NPC64141
0.7204	Intermediate Similarity	NPC96795
0.7204	Intermediate Similarity	NPC264632
0.7126	Intermediate Similarity	NPC205195
0.7041	Intermediate Similarity	NPC64195
0.6832	Remote Similarity	NPC229505
0.6829	Remote Similarity	NPC287597
0.6517	Remote Similarity	NPC235294
0.6279	Remote Similarity	NPC34293
0.6277	Remote Similarity	NPC476383
0.625	Remote Similarity	NPC94871
0.6186	Remote Similarity	NPC205864
0.6186	Remote Similarity	NPC247032
0.6154	Remote Similarity	NPC260425
0.6147	Remote Similarity	NPC257970
0.6022	Remote Similarity	NPC321638
0.596	Remote Similarity	NPC600370
0.5882	Remote Similarity	NPC141455
0.5833	Remote Similarity	NPC76406
0.5806	Remote Similarity	NPC81515
0.5773	Remote Similarity	NPC611289
0.5747	Remote Similarity	NPC229784
0.566	Remote Similarity	NPC471062
0.5648	Remote Similarity	NPC473427
0.5632	Remote Similarity	NPC288416
0.5575	Remote Similarity	NPC470927
0.5567	Remote Similarity	NPC68092
0.5556	Remote Similarity	NPC47471
0.5545	Remote Similarity	NPC298257
0.5545	Remote Similarity	NPC175214
0.5464	Remote Similarity	NPC472350
0.5464	Remote Similarity	NPC197316
0.5464	Remote Similarity	NPC89105
0.5361	Remote Similarity	NPC483706
0.5333	Remote Similarity	NPC300894
0.5333	Remote Similarity	NPC23845
0.5234	Remote Similarity	NPC476384
0.5234	Remote Similarity	NPC106818
0.5165	Remote Similarity	NPC886
0.5155	Remote Similarity	NPC220942
0.5146	Remote Similarity	NPC269141
0.5133	Remote Similarity	NPC188393
0.5096	Remote Similarity	NPC105005
0.5045	Remote Similarity	NPC87403

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476397 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5572
0.1-0.2	3534
0.2-0.3	42
0.3-0.4	1
0.4-0.5	0
0.5-0.6	1
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
0.5464	Remote Similarity	NPD7266	Phase 2

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