NPASS Compound

Natural Product: NPC477580

Natural Product ID	NPC477580
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3-[(3S,5S,8R,9S,10S,13R,14S,17R)-14-hydroxy-3-[(2R,4R,5S,6R)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]cyclopent-2-en-1-one
IUPAC Name	3-[(3S,5S,8R,9S,10S,13R,14S,17R)-14-hydroxy-3-[(2R,4R,5S,6R)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]cyclopent-2-en-1-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	44425146
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001013] Steroidal glycosides

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 85 90 0 0 0 0 0 0 0 0999 V2000 5.9266 1.0358 1.7134 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6723 -0.2634 1.6581 C 0 0 2 0 0 0 0 0 0 0 0 0 7.6928 -0.2949 0.5323 C 0 0 1 0 0 0 0 0 0 0 0 0 6.9114 -0.3025 -0.7626 C 0 0 1 0 0 0 0 0 0 0 0 0 5.9540 -1.4364 -0.7607 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1479 -1.5776 0.5052 C 0 0 1 0 0 0 0 0 0 0 0 0 5.8817 -1.3794 1.6559 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9901 -0.8023 0.4768 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8270 -1.5679 0.4935 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9963 -1.3223 1.7305 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0585 -0.1634 1.6110 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2739 -0.1265 0.3440 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5652 -1.4160 -0.4112 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0115 -1.4064 -0.7724 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2726 -1.5925 -1.6284 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7713 -1.3890 -1.3554 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8890 0.0043 -0.7803 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1913 -0.0823 0.5620 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7208 0.9850 1.4433 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1659 0.5397 1.7131 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0078 0.6903 0.4539 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2064 0.6339 -0.7999 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.1907 0.0159 -1.7742 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8792 -1.0492 -0.9794 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0646 -0.3523 0.3649 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.4649 0.1169 0.4000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2843 -0.2684 1.4053 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6025 0.3084 1.2377 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.6693 -0.0234 1.8060 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.4695 1.3879 0.2518 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2392 0.9507 -0.5189 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0633 1.9718 -1.2557 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6600 2.0489 0.5988 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7031 1.0834 -0.4579 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3660 0.9284 -1.0363 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9000 1.5066 -2.1694 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5783 0.7482 0.6339 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4254 1.1057 2.7060 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1604 1.1643 0.9514 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6863 1.8518 1.6885 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2868 -0.3140 2.6055 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2428 -1.2405 0.6046 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6753 -0.5124 -1.5689 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5440 -2.3807 -0.8964 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2594 -1.3661 -1.6148 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8060 -2.6427 0.5342 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1361 -2.6328 0.5262 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5220 -2.2515 2.0498 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7339 -1.0556 2.5436 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5748 0.8081 1.7830 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3240 -0.2522 2.4545 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3862 -2.2462 0.2918 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3511 -0.4915 -1.2840 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1904 -2.2456 -1.4921 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0192 -0.8964 -2.4421 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1473 -2.6109 -2.0011 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2674 -1.5570 -2.3004 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0019 -2.1156 -0.5478 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1824 0.6194 -1.4211 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4948 -1.0634 1.0128 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8231 1.9843 0.9362 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2006 1.1349 2.3880 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5420 1.1204 2.5552 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1083 -0.5433 1.9379 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7719 -0.2866 -2.7261 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9573 0.7970 -2.0221 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8567 -1.2491 -1.4747 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3633 -2.0037 -0.9071 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8427 -1.1180 1.1407 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0207 -0.9127 2.2280 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3279 2.3918 0.7160 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3347 1.4840 -0.4354 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6296 0.3729 -1.3942 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7819 1.8399 -0.9207 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0109 1.9192 -2.2248 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9985 2.7049 1.2529 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6185 2.0416 1.1111 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6469 2.6128 -0.3711 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6674 1.4940 -0.0447 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8382 0.8820 -1.5205 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0255 1.9179 -0.3527 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7211 0.8643 -3.0471 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9852 1.7026 -2.1035 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4022 2.4950 -2.3300 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4113 0.5403 1.1213 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 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 23 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 28 30 1 0 30 31 1 0 22 32 1 6 21 33 1 1 12 34 1 6 4 35 1 0 35 36 1 0 3 37 1 0 7 2 1 0 14 9 1 0 18 12 1 0 22 17 1 0 25 21 1 0 31 26 1 0 1 38 1 0 1 39 1 0 1 40 1 0 2 41 1 1 3 42 1 1 4 43 1 6 5 44 1 0 5 45 1 0 6 46 1 1 9 47 1 1 10 48 1 0 10 49 1 0 11 50 1 0 11 51 1 0 13 52 1 1 14 53 1 0 14 54 1 0 15 55 1 0 15 56 1 0 16 57 1 0 16 58 1 0 17 59 1 6 18 60 1 1 19 61 1 0 19 62 1 0 20 63 1 0 20 64 1 0 23 65 1 0 23 66 1 0 24 67 1 0 24 68 1 0 25 69 1 1 27 70 1 0 30 71 1 0 30 72 1 0 31 73 1 0 31 74 1 0 32 75 1 0 33 76 1 0 33 77 1 0 33 78 1 0 34 79 1 0 34 80 1 0 34 81 1 0 36 82 1 0 36 83 1 0 36 84 1 0 37 85 1 0 M END

Standard InCHIKey	DASJJOOKVLPCQK-RHLYVVHBSA-N
Standard InCHI	InChI=1S/C31H48O6/c1-18-28(33)26(35-4)17-27(36-18)37-22-9-12-29(2)20(16-22)6-8-25-24(29)10-13-30(3)23(11-14-31(25,30)34)19-5-7-21(32)15-19/h15,18,20,22-28,33-34H,5-14,16-17H2,1-4H3/t18-,20+,22+,23-,24+,25-,26-,27+,28+,29+,30-,31+/m1/s1
SMILES	C[C@@H]1[C@@H]([C@@H](C[C@@H](O1)O[C@H]2CC[C@]3([C@H](C2)CC[C@@H]4[C@@H]3CC[C@]5([C@@]4(CC[C@@H]5C6=CC(=O)CC6)O)C)C)OC)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	516.35	Volume:	540.862 ? Van der Waals volume.
Dense:	0.955	LogP:	3.897 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.749 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.921 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	32.0
TPSA:	85.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	6.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.515	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.028	Fsp³:	0.903
MCE-18:	106.915 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.798	Fluc inhibitor:	0.007 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.014 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.238	Promiscuous compounds:	0.622

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.208	MDCK Permeability:	-5.061
Pgp-inhibitor:	0.944	Pgp-substrate:	0.374
PAMPA:	0.356 ? 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):	0.001
20% Bioavailability (F20%):	0.394	30% Bioavailability (F30%):	0.419
50% Bioavailability (F50%):	0.928

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.011	MRP1:	0.767
Plasma Protein Binding (PPB):	93.43%	Volume Distribution (VD):	0.26
Fu:	5.934% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.945	BCRP inhibitor:	0.659
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.958	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.016	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.088
HLM stability:	0.669 ? 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):

11.862

Half-life (T1/2):

1.89

ADMET: Toxicity

hERG Blockers:	0.082	hERG Blockers (10um):	0.341
Human Hepatotoxicity (H-HT):	0.571	Drug-induced Liver Injury (DILI):	0.91
AMES Toxicity:	0.884	Rat Oral Acute Toxicity:	0.716
Maximum Recommended Daily Dose:	0.928	Skin Sensitization:	0.997
Carcinogencity:	0.901	Eye Corrosion:	0.001
Eye Irritation:	0.182	Respiratory Toxicity:	0.913
Drug-induced Neurotoxicity:	0.177	Ototoxicity:	0.65
Hematotoxicity:	0.72	Drug-induced Nephrotoxicity:	0.858
Genotoxicity:	0.687	RPMI-8226 Immunitoxicity:	0.184
A549 Cytotoxicity:	0.894	Hek293 Cytotoxicity:	0.903
BCF:	1.683 ? 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:	3.884 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.22 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.659 ? 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
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	leaves	Niigata City, Niigata Province, Japan	2000-Nov	PMID[15730243]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	leaves	n.a.	n.a.	PMID[16933868]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17253842]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	stems and twigs	Niigata City, Niigata Province, Japan	2001-NOV	PMID[17595134]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	stems and twigs	n.a.	n.a.	PMID[17595134]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29693393]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	Leaves; Stems	n.a.	n.a.	PMID[9214727]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10021	Nerium oleander	Species	Apocynaceae	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
IC50	6
Activity	3

Activity Type	# Activity
Cell line	5
Others	4

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
NPT1475	Cell line	WI-38 VA13	Homo sapiens	IC50	=	1300000	nM	PMID[17595134]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	10200000	nM	PMID[17595134]
NPT81	Cell line	A549	Homo sapiens	IC50	=	1800	nM	PMID[17595134]
NPT81	Cell line	A549	Homo sapiens	IC50	=	2100	nM	PMID[17595134]
NPT81	Cell line	A549	Homo sapiens	IC50	>	316000	nM	PMID[17595134]
NPT27	Others	Unspecified	n.a.	IC50	=	370000	nM	PMID[17595134]
NPT2	Others	Unspecified	n.a.	Activity	=	78	%	PMID[17595134]
NPT2	Others	Unspecified	n.a.	Activity	=	67	%	PMID[17595134]
NPT2	Others	Unspecified	n.a.	Activity	=	58	%	PMID[17595134]

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 NPC477580 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	15121
0.1-0.2	30553
0.2-0.3	3887
0.3-0.4	175
0.4-0.5	88
0.5-0.6	22
0.6-0.7	6
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	Natural Product ID
0.7375	Intermediate Similarity	NPC84949
0.7375	Intermediate Similarity	NPC480562
0.7375	Intermediate Similarity	NPC74945
0.7375	Intermediate Similarity	NPC31354
0.7375	Intermediate Similarity	NPC69576
0.6429	Remote Similarity	NPC99080
0.6207	Remote Similarity	NPC483822
0.6	Remote Similarity	NPC103534
0.6	Remote Similarity	NPC44899
0.6	Remote Similarity	NPC304260
0.6	Remote Similarity	NPC29639
0.5843	Remote Similarity	NPC484202
0.5632	Remote Similarity	NPC471633
0.5618	Remote Similarity	NPC199428
0.5618	Remote Similarity	NPC109448
0.5618	Remote Similarity	NPC310341
0.5568	Remote Similarity	NPC481208
0.5506	Remote Similarity	NPC34390
0.5495	Remote Similarity	NPC93883
0.5476	Remote Similarity	NPC246399
0.5476	Remote Similarity	NPC34977
0.5476	Remote Similarity	NPC221196
0.5465	Remote Similarity	NPC39485
0.5385	Remote Similarity	NPC180079
0.5361	Remote Similarity	NPC55532
0.5281	Remote Similarity	NPC99620
0.5275	Remote Similarity	NPC152615
0.5213	Remote Similarity	NPC72260
0.5111	Remote Similarity	NPC479351
0.5111	Remote Similarity	NPC479352
0.5104	Remote Similarity	NPC481207
0.5096	Remote Similarity	NPC475419
0.5052	Remote Similarity	NPC481206

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC477580 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6204
0.1-0.2	2712
0.2-0.3	221
0.3-0.4	3
0.4-0.5	6
0.5-0.6	3
0.6-0.7	1
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
0.6022	Remote Similarity	NPD8377	Phase 4
0.5213	Remote Similarity	NPD8294	Phase 4
0.5152	Remote Similarity	NPD8378	Pre-clinical
0.5152	Remote Similarity	NPD8379	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