NPASS Compound

Natural Product: NPC133849

Natural Product ID	NPC133849
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	CEXRTAGZMFHGHD-IOWSJCHKSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000254] Ethers [CHEMONTID:0002463] Diarylethers

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 84 90 0 0 0 0 0 0 0 0999 V2000 -5.8965 -2.7108 -1.3172 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5655 -2.5000 -0.8566 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.2014 -3.0585 0.3730 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8029 -1.9821 1.3834 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5953 -1.3614 0.8096 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4455 -1.1760 1.4916 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3130 -0.6517 0.8416 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3827 -0.3278 -0.4922 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5408 -0.5108 -1.1729 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6747 -1.0329 -0.5388 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9320 -1.2964 -1.2689 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.9275 -0.1660 -1.0611 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2871 1.0952 -0.6400 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5293 1.7537 -1.5724 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8476 2.8619 -1.2059 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9407 3.2891 0.1020 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6715 2.6896 1.0475 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3768 1.5413 0.6628 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1359 4.4680 0.4086 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7815 4.0506 0.0491 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2062 4.4512 -1.1112 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0444 3.9907 -1.4246 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6886 3.1430 -0.5676 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1005 2.7604 0.6016 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1639 3.2149 0.9346 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9601 2.5550 -0.9971 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5810 1.5092 -0.2013 C 0 0 2 0 0 0 0 0 0 0 0 0 3.1477 0.1091 -0.2268 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1821 -0.7892 0.2052 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3970 -0.0769 0.6954 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0411 1.0443 1.6334 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0212 1.9448 1.1128 N 0 0 0 0 0 0 0 0 0 0 0 0 4.5076 3.3110 1.0816 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0713 -2.1359 0.2314 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8922 -2.6882 -0.1807 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8935 -1.8619 -0.5921 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0034 -0.4575 -0.6183 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7992 0.1781 -1.0733 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6681 -2.4043 -1.0258 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5186 -2.8051 -2.3878 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7664 -4.0706 -0.1609 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7789 -4.9348 0.2575 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8421 -0.4697 1.5358 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9415 -0.7927 2.8977 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3448 -1.7997 -1.7242 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9991 -3.5878 -1.9946 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5191 -2.9792 -0.4140 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9706 -3.7351 0.8190 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2575 -3.6823 0.2710 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6164 -1.2562 1.4501 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5884 -2.4585 2.3770 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3843 -1.4312 2.5532 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5832 -0.2542 -2.2187 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6962 -1.2924 -2.3669 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4680 0.0026 -2.0498 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7434 -0.4048 -0.3646 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4814 1.3915 -2.5775 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2567 3.3949 -1.9083 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7428 3.0279 2.0434 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9671 1.0672 1.4256 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7004 5.1238 -1.7767 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5037 4.3029 -2.3420 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6578 2.0957 1.2635 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6141 2.9177 1.8376 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8729 2.2086 -2.0966 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7469 3.3845 -1.1390 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6672 1.4105 -0.7209 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0847 0.1858 -0.0990 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9475 -0.8282 1.3387 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7271 0.6791 2.6302 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9535 1.6529 1.7865 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6714 3.9740 0.8068 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9778 3.6076 2.0195 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2487 3.3713 0.2388 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9121 -2.7559 0.5761 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4415 -3.2845 -2.7796 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2141 -1.9433 -3.0063 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2977 -3.5476 -2.4120 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6348 -4.8636 -0.4520 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1157 -4.7371 1.2909 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3639 -5.9807 0.1758 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6767 -1.8625 3.1118 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9619 -0.6393 3.2692 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2228 -0.1744 3.4954 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 16 19 1 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 23 26 1 0 26 27 1 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 29 34 1 0 34 35 2 0 35 36 1 0 36 37 2 0 37 38 1 0 36 39 1 0 39 40 1 0 35 41 1 0 41 42 1 0 7 43 1 0 43 44 1 0 11 2 1 0 18 13 1 0 25 20 1 0 32 27 1 0 10 5 1 0 37 28 1 0 38 8 1 0 1 45 1 0 1 46 1 0 1 47 1 0 3 48 1 0 3 49 1 0 4 50 1 0 4 51 1 0 6 52 1 0 9 53 1 0 11 54 1 6 12 55 1 0 12 56 1 0 14 57 1 0 15 58 1 0 17 59 1 0 18 60 1 0 21 61 1 0 22 62 1 0 24 63 1 0 25 64 1 0 26 65 1 0 26 66 1 0 27 67 1 6 30 68 1 0 30 69 1 0 31 70 1 0 31 71 1 0 33 72 1 0 33 73 1 0 33 74 1 0 34 75 1 0 40 76 1 0 40 77 1 0 40 78 1 0 42 79 1 0 42 80 1 0 42 81 1 0 44 82 1 0 44 83 1 0 44 84 1 0 M END

Standard InCHIKey	CEXRTAGZMFHGHD-IOWSJCHKSA-N
Standard InCHI	InChI=1S/C37H40N2O5/c1-38-16-14-25-20-32(40-3)33-22-29(25)30(38)18-23-6-10-27(11-7-23)43-28-12-8-24(9-13-28)19-31-35-26(15-17-39(31)2)21-34(41-4)36(42-5)37(35)44-33/h6-13,20-22,30-31H,14-19H2,1-5H3/t30-,31+/m0/s1
SMILES	CN1CCc2cc(c3cc2[C@@H]1Cc1ccc(cc1)Oc1ccc(cc1)C[C@@H]1c2c(CCN1C)cc(c(c2O3)OC)OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	592.29	Volume:	622.92 ? Van der Waals volume.
Dense:	0.951	LogP:	3.755 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.23 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.566 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	42.0
TPSA:	52.63 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	0.0	Rings:	9.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.25	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.739	Fsp³:	0.351
MCE-18:	126.16 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.999	Fluc inhibitor:	0.217 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.648 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.922 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.297

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.58	MDCK Permeability:	-4.695
Pgp-inhibitor:	0.898	Pgp-substrate:	0.419
PAMPA:	0.003 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.0
20% Bioavailability (F20%):	0.263	30% Bioavailability (F30%):	0.078
50% Bioavailability (F50%):	0.981

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.984	MRP1:	0.974
Plasma Protein Binding (PPB):	83.113%	Volume Distribution (VD):	0.257
Fu:	19.281% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.852
OATP1B3 inhibitor:	0.959	BCRP inhibitor:	0.868
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.004
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.999	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	0.888
CYP2B6-substrate:	0.982	CYP2C8-inhibitor:	0.139
HLM stability:	0.671 ? 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):

8.094

Half-life (T1/2):

2.166

ADMET: Toxicity

hERG Blockers:	0.878	hERG Blockers (10um):	0.848
Human Hepatotoxicity (H-HT):	0.57	Drug-induced Liver Injury (DILI):	0.009
AMES Toxicity:	0.644	Rat Oral Acute Toxicity:	0.729
Maximum Recommended Daily Dose:	0.964	Skin Sensitization:	0.511
Carcinogencity:	0.703	Eye Corrosion:	0.0
Eye Irritation:	0.005	Respiratory Toxicity:	0.806
Drug-induced Neurotoxicity:	0.9	Ototoxicity:	0.443
Hematotoxicity:	0.083	Drug-induced Nephrotoxicity:	0.292
Genotoxicity:	0.562	RPMI-8226 Immunitoxicity:	0.061
A549 Cytotoxicity:	0.173	Hek293 Cytotoxicity:	0.61
BCF:	2.337 ? 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:	4.557 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.12 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.439 ? 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
NPO8212	Ligularia nelumbifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12088436]
NPO25510	Plectranthus ernstii	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19445517]
NPO8212	Ligularia nelumbifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22472691]
NPO28026	Grifola frondosa	Species	Schizophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO435	Bohadschia marmorata	Species	Holothuriidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO595	Tephrosia falciformis	Species	Geometridae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8077	Artocarpus incisa	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25510	Plectranthus ernstii	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8212	Ligularia nelumbifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1114	Cetraria australiensis	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28026	Grifola frondosa	Species	Schizophyllaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO859	Berberis oblonga	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO859	Berberis oblonga	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8212	Ligularia nelumbifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8077	Artocarpus incisa	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO435	Bohadschia marmorata	Species	Holothuriidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25510	Plectranthus ernstii	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8077	Artocarpus incisa	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8212	Ligularia nelumbifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO595	Tephrosia falciformis	Species	Geometridae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10518	Chrysanthemum myconis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1114	Cetraria australiensis	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO859	Berberis oblonga	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28026	Grifola frondosa	Species	Schizophyllaceae	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

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

In vivo activity

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

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC133849 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	34585
0.1-0.2	14498
0.2-0.3	517
0.3-0.4	119
0.4-0.5	31
0.5-0.6	41
0.6-0.7	25
0.7-0.8	1
0.8-0.85	6
0.85-0.9	1
0.9-0.95	6
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.918	High Similarity	NPC76682
0.918	High Similarity	NPC10908
0.918	High Similarity	NPC63646
0.918	High Similarity	NPC317145
0.918	High Similarity	NPC198498
0.918	High Similarity	NPC115284
0.873	High Similarity	NPC276890
0.8209	Intermediate Similarity	NPC480587
0.8116	Intermediate Similarity	NPC185639
0.8116	Intermediate Similarity	NPC251735
0.8116	Intermediate Similarity	NPC49075
0.8116	Intermediate Similarity	NPC599951
0.8103	Intermediate Similarity	NPC317439
0.7941	Intermediate Similarity	NPC73492
0.7941	Intermediate Similarity	NPC299990
0.7857	Intermediate Similarity	NPC223690
0.7857	Intermediate Similarity	NPC9532
0.7647	Intermediate Similarity	NPC12424
0.7647	Intermediate Similarity	NPC129518
0.7647	Intermediate Similarity	NPC251580
0.7536	Intermediate Similarity	NPC603853
0.75	Intermediate Similarity	NPC227060
0.7273	Intermediate Similarity	NPC480590
0.7222	Intermediate Similarity	NPC311973
0.7183	Intermediate Similarity	NPC290582
0.7183	Intermediate Similarity	NPC217748
0.7183	Intermediate Similarity	NPC182052
0.7183	Intermediate Similarity	NPC271013
0.7183	Intermediate Similarity	NPC42663
0.7183	Intermediate Similarity	NPC15414
0.7143	Intermediate Similarity	NPC247639
0.7143	Intermediate Similarity	NPC25084
0.7123	Intermediate Similarity	NPC116465
0.7105	Intermediate Similarity	NPC24260
0.7083	Intermediate Similarity	NPC279228
0.7067	Intermediate Similarity	NPC16357
0.7067	Intermediate Similarity	NPC302245
0.7051	Intermediate Similarity	NPC480586
0.6986	Remote Similarity	NPC239824
0.6753	Remote Similarity	NPC212237
0.6753	Remote Similarity	NPC475479
0.6667	Remote Similarity	NPC254441
0.6667	Remote Similarity	NPC611658
0.6579	Remote Similarity	NPC274716
0.6579	Remote Similarity	NPC167116
0.6579	Remote Similarity	NPC609821
0.6538	Remote Similarity	NPC243454
0.6538	Remote Similarity	NPC323537
0.6494	Remote Similarity	NPC181796
0.6494	Remote Similarity	NPC290005
0.6494	Remote Similarity	NPC54654
0.6494	Remote Similarity	NPC7715
0.6494	Remote Similarity	NPC328155
0.6494	Remote Similarity	NPC222661
0.6494	Remote Similarity	NPC285931
0.6456	Remote Similarity	NPC485712
0.641	Remote Similarity	NPC195538
0.6389	Remote Similarity	NPC41376
0.6364	Remote Similarity	NPC229373
0.6133	Remote Similarity	NPC480591
0.6098	Remote Similarity	NPC10871
0.6081	Remote Similarity	NPC603603
0.6066	Remote Similarity	NPC314682
0.5952	Remote Similarity	NPC206900
0.5952	Remote Similarity	NPC281581
0.5915	Remote Similarity	NPC317272
0.5915	Remote Similarity	NPC268503
0.589	Remote Similarity	NPC256012
0.589	Remote Similarity	NPC610965
0.5882	Remote Similarity	NPC104196
0.5882	Remote Similarity	NPC485711
0.5769	Remote Similarity	NPC608819
0.5747	Remote Similarity	NPC41122
0.5747	Remote Similarity	NPC318805
0.5732	Remote Similarity	NPC139783
0.5732	Remote Similarity	NPC65312
0.5732	Remote Similarity	NPC611798
0.5714	Remote Similarity	NPC213206
0.5714	Remote Similarity	NPC188163
0.5714	Remote Similarity	NPC328750
0.5696	Remote Similarity	NPC112248
0.5663	Remote Similarity	NPC8836
0.5663	Remote Similarity	NPC275680
0.5663	Remote Similarity	NPC249996
0.5663	Remote Similarity	NPC22115
0.5529	Remote Similarity	NPC239584
0.55	Remote Similarity	NPC475393
0.5422	Remote Similarity	NPC302275
0.5405	Remote Similarity	NPC30779
0.5402	Remote Similarity	NPC11296
0.5402	Remote Similarity	NPC254581
0.5402	Remote Similarity	NPC274661
0.5402	Remote Similarity	NPC82457
0.5393	Remote Similarity	NPC475597
0.5385	Remote Similarity	NPC240841
0.5309	Remote Similarity	NPC286119
0.5309	Remote Similarity	NPC600054
0.5309	Remote Similarity	NPC601504
0.5224	Remote Similarity	NPC185838
0.5217	Remote Similarity	NPC135538
0.5217	Remote Similarity	NPC24233
0.519	Remote Similarity	NPC610959
0.5165	Remote Similarity	NPC234318
0.5122	Remote Similarity	NPC600872

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC133849 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5010
0.1-0.2	4003
0.2-0.3	121
0.3-0.4	9
0.4-0.5	2
0.5-0.6	2
0.6-0.7	0
0.7-0.8	1
0.8-0.85	1
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.918	High Similarity	NPD8099	Discontinued
0.8333	Intermediate Similarity	NPD8156	Discontinued
0.7429	Intermediate Similarity	NPD8095	Phase 1
0.5714	Remote Similarity	NPD4664	Clinical (unspecified phase)
0.5165	Remote Similarity	NPD8053	Approved

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