NPASS Compound

Natural Product: NPC469752

Natural Product ID	NPC469752
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Antialloside
IUPAC Name	(3S,5S,8R,9S,10S,12R,13S,14S,17R)-5,12,14-trihydroxy-13-methyl-17-(5-oxo-2H-furan-3-yl)-3-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-2,3,4,6,7,8,9,11,12,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-10-carbaldehyde
Synonyms	Antialloside
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1169681
PubChem CID	49799519
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides and derivatives

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 82 87 0 0 0 0 0 0 0 0999 V2000 0.9256 1.8581 -2.0852 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3038 0.7888 -2.0023 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1060 0.2192 -0.6458 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8169 1.1315 0.3289 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0085 0.5922 0.9989 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8385 -0.4026 0.2685 C 0 0 1 0 0 0 0 0 0 0 0 0 2.1692 -1.0055 -0.9418 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7039 -1.1744 -0.6871 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1549 -1.7898 -1.8395 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3651 -2.0080 0.4874 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7835 -1.4541 1.3369 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8395 -1.0215 0.3815 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3769 0.1773 -0.3773 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2432 0.2586 -1.6115 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6234 -0.2634 -1.3913 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7183 -1.5642 -1.8819 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1330 -0.2526 0.0209 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1735 -0.7717 1.0271 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5545 -2.0247 1.5667 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1140 0.1720 2.1739 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9022 1.3714 1.7665 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5912 1.1047 0.4652 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.0682 1.2748 0.5149 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8213 1.5142 1.5838 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2389 1.6117 1.2000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2439 1.8306 1.9272 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.2809 1.4158 -0.1547 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9644 1.2770 -0.6614 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3597 -1.1600 0.0129 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1402 0.0039 0.0005 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1077 -0.7376 0.6056 C 0 0 1 0 0 0 0 0 0 0 0 0 5.8770 -1.3222 -0.4203 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1498 -0.3569 -1.4110 C 0 0 2 0 0 0 0 0 0 0 0 0 6.6977 -1.0403 -2.6214 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2603 0.5167 -0.8148 C 0 0 2 0 0 0 0 0 0 0 0 0 6.6282 1.1999 0.3804 C 0 0 2 0 0 0 0 0 0 0 0 0 6.0456 0.1895 1.3505 C 0 0 1 0 0 0 0 0 0 0 0 0 5.3890 0.9149 2.3413 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5381 1.9446 -0.1228 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6829 1.4868 -1.7004 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0387 0.3665 -2.9285 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0563 1.4141 1.1105 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0712 2.1141 -0.1405 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7310 0.2460 2.0385 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7044 1.4635 1.2256 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9749 -1.2840 0.9679 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3044 -0.4022 -1.8566 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6233 -1.9981 -1.1426 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6099 -2.6559 -2.0315 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1808 -2.2135 1.2052 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0084 -3.0320 0.1680 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1741 -2.3168 1.9477 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4538 -0.7116 2.0583 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0046 -1.8731 -0.3295 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6071 1.1027 0.2245 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8204 -0.3442 -2.4494 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3144 1.2990 -1.9869 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3488 0.3474 -2.0032 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6018 -1.4890 -2.8754 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9180 -1.9387 2.4758 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0693 0.4335 2.4992 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5617 -0.2576 3.1201 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5760 1.7393 2.5777 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2201 2.2701 1.5955 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1979 1.8251 -0.3356 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5496 1.6348 2.6228 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9572 0.3985 -1.2871 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7306 2.1425 -1.3393 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0441 -2.1332 0.4976 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1836 -0.7911 0.6213 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6257 -1.4802 -1.0227 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7624 -1.5664 1.2306 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2625 0.2495 -1.5851 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4150 -0.3648 -3.1288 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9267 -1.2865 -3.3755 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2750 -1.9496 -2.3247 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0847 -0.1196 -0.4310 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3302 1.8585 0.9207 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8574 -0.3864 1.8569 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7434 0.3676 2.8360 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1753 2.5726 0.5335 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0221 2.2448 -1.1651 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 3 2 1 6 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 6 8 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 15 17 1 0 17 18 1 0 18 19 1 1 18 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 25 27 1 0 27 28 1 0 17 29 1 6 6 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 33 35 1 0 35 36 1 0 36 37 1 0 37 38 1 0 36 39 1 0 35 40 1 0 13 3 1 0 22 17 1 0 28 23 1 0 37 31 1 0 8 3 1 0 18 12 1 0 2 41 1 0 4 42 1 0 4 43 1 0 5 44 1 0 5 45 1 0 6 46 1 1 7 47 1 0 7 48 1 0 9 49 1 0 10 50 1 0 10 51 1 0 11 52 1 0 11 53 1 0 12 54 1 6 13 55 1 1 14 56 1 0 14 57 1 0 15 58 1 6 16 59 1 0 19 60 1 0 20 61 1 0 20 62 1 0 21 63 1 0 21 64 1 0 22 65 1 6 24 66 1 0 28 67 1 0 28 68 1 0 29 69 1 0 29 70 1 0 29 71 1 0 31 72 1 1 33 73 1 6 34 74 1 0 34 75 1 0 34 76 1 0 35 77 1 1 36 78 1 1 37 79 1 1 38 80 1 0 39 81 1 0 40 82 1 0 M END

Standard InCHIKey	MFIXZHBJWSBQJA-NCKLWLLBSA-N
Standard InCHI	InChI=1S/C29H42O11/c1-14-22(33)23(34)24(35)25(39-14)40-16-3-6-27(13-30)19-10-20(31)26(2)17(15-9-21(32)38-12-15)5-8-29(26,37)18(19)4-7-28(27,36)11-16/h9,13-14,16-20,22-25,31,33-37H,3-8,10-12H2,1-2H3/t14-,16+,17-,18-,19+,20-,22-,23-,24-,25-,26+,27+,28+,29+/m1/s1
SMILES	O=C[C@@]12CC[C@@H](C[C@@]2(O)CC[C@@H]2[C@@H]1C[C@@H](O)[C@]1([C@]2(O)CC[C@@H]1C1=CC(=O)OC1)C)O[C@H]1O[C@H](C)[C@H]([C@H]([C@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	566.27	Volume:	547.584 ? Van der Waals volume.
Dense:	1.034	LogP:	-0.878 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.167 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.785 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	33.0
TPSA:	183.21 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	6.0	Rings:	6.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.149	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.511	Fsp³:	0.862
MCE-18:	119.778 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.636	Fluc inhibitor:	0.006 ? 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:	0.141	Promiscuous compounds:	0.355

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.324	MDCK Permeability:	-5.281
Pgp-inhibitor:	0.0	Pgp-substrate:	1.0
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):	0.147
20% Bioavailability (F20%):	0.661	30% Bioavailability (F30%):	0.558
50% Bioavailability (F50%):	0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.008	MRP1:	0.735
Plasma Protein Binding (PPB):	26.237%	Volume Distribution (VD):	-0.595
Fu:	79.662% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.922
OATP1B3 inhibitor:	0.889	BCRP inhibitor:	0.004
BSEP inhibitor:	0.005

ADMET: Metabolism

CYP1A2-inhibitor:	0.02	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.077	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.009	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.007
HLM stability:	0.266 ? 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):

1.342

Half-life (T1/2):

3.673

ADMET: Toxicity

hERG Blockers:	0.135	hERG Blockers (10um):	0.617
Human Hepatotoxicity (H-HT):	0.697	Drug-induced Liver Injury (DILI):	0.347
AMES Toxicity:	0.919	Rat Oral Acute Toxicity:	0.996
Maximum Recommended Daily Dose:	1.0	Skin Sensitization:	1.0
Carcinogencity:	0.968	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.999
Drug-induced Neurotoxicity:	0.008	Ototoxicity:	0.642
Hematotoxicity:	0.716	Drug-induced Nephrotoxicity:	0.989
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.948
A549 Cytotoxicity:	0.949	Hek293 Cytotoxicity:	0.995
BCF:	0.514 ? 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:	3.16 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.617 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.828 ? 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
NPO8369	Antiaris toxicaria	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20553004]
NPO8369	Antiaris toxicaria	Species	Moraceae	Eukaryota	latex	Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Yunnan Province, China	2011-Mar	PMID[24033101]
NPO8369	Antiaris toxicaria	Species	Moraceae	Eukaryota	trunk bark	Yunnan, China	n.a.	PMID[24582402]
NPO8369	Antiaris toxicaria	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8369	Antiaris toxicaria	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8369	Antiaris toxicaria	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8369	Antiaris toxicaria	Species	Moraceae	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
Activity	2
Ratio	1
Inhibition	1
ED50	10

Activity Type	# Activity
Cell line	7
Non-molecular	7

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
NPT147	Cell line	SK-MEL-2	Homo sapiens	ED50	=	0.12	ug ml-1	PMID[16643036]
NPT308	Cell line	CAKI-1	Homo sapiens	ED50	=	0.068	ug ml-1	PMID[23376010]
NPT309	Cell line	1A9	Homo sapiens	ED50	=	0.062	ug ml-1	PMID[23190013]
NPT306	Cell line	PC-3	Homo sapiens	ED50	=	0.085	ug ml-1	PMID[23190013]
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	0.12	ug ml-1	PMID[24063582]
NPT81	Cell line	A549	Homo sapiens	ED50	=	0.046	ug ml-1	PMID[24063582]
NPT91	Cell line	KB	Homo sapiens	ED50	=	0.065	ug ml-1	PMID[20231390]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	0.25	uM	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	350.0	%	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Ratio	=	80.0	n.a.	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	70.7	%	PMID[24033101]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.11	ug ml-1	PMID[24582402]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.15	ug ml-1	PMID[24582402]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.075	ug ml-1	PMID[24582402]

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 NPC469752 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	17408
0.1-0.2	27172
0.2-0.3	4776
0.3-0.4	302
0.4-0.5	110
0.5-0.6	41
0.6-0.7	21
0.7-0.8	0
0.8-0.85	8
0.85-0.9	3
0.9-0.95	0
0.95-1	7

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC9499
1.0	High Similarity	NPC471360
1.0	High Similarity	NPC469751
1.0	High Similarity	NPC471361
1.0	High Similarity	NPC86159
1.0	High Similarity	NPC469754
1.0	High Similarity	NPC70542
0.8571	High Similarity	NPC77319
0.8571	High Similarity	NPC471351
0.8571	High Similarity	NPC471355
0.8354	Intermediate Similarity	NPC471354
0.8354	Intermediate Similarity	NPC27507
0.8077	Intermediate Similarity	NPC17896
0.8077	Intermediate Similarity	NPC469755
0.8077	Intermediate Similarity	NPC284406
0.8077	Intermediate Similarity	NPC197707
0.8077	Intermediate Similarity	NPC251866
0.8	Intermediate Similarity	NPC471359
0.7778	Intermediate Similarity	NPC179412
0.7778	Intermediate Similarity	NPC471356
0.7683	Intermediate Similarity	NPC469753
0.7349	Intermediate Similarity	NPC471353
0.716	Intermediate Similarity	NPC99728
0.716	Intermediate Similarity	NPC87250
0.716	Intermediate Similarity	NPC244402
0.716	Intermediate Similarity	NPC50305
0.6988	Remote Similarity	NPC157376
0.6988	Remote Similarity	NPC142066
0.6988	Remote Similarity	NPC603972
0.6667	Remote Similarity	NPC219085
0.663	Remote Similarity	NPC469749
0.6484	Remote Similarity	NPC32793
0.6484	Remote Similarity	NPC116075
0.641	Remote Similarity	NPC469794
0.6395	Remote Similarity	NPC469750
0.6304	Remote Similarity	NPC471357
0.6304	Remote Similarity	NPC469757
0.6304	Remote Similarity	NPC117702
0.6279	Remote Similarity	NPC84987
0.6211	Remote Similarity	NPC146857
0.6163	Remote Similarity	NPC99620
0.6136	Remote Similarity	NPC10823
0.6092	Remote Similarity	NPC309034
0.6067	Remote Similarity	NPC180079
0.6042	Remote Similarity	NPC247190
0.6	Remote Similarity	NPC59288
0.6	Remote Similarity	NPC208193
0.5978	Remote Similarity	NPC173555
0.5957	Remote Similarity	NPC608063
0.5955	Remote Similarity	NPC76572
0.5955	Remote Similarity	NPC193382
0.5889	Remote Similarity	NPC83287
0.5862	Remote Similarity	NPC158344
0.5862	Remote Similarity	NPC474418
0.5843	Remote Similarity	NPC6108
0.5843	Remote Similarity	NPC89514
0.5784	Remote Similarity	NPC329675
0.5784	Remote Similarity	NPC194716
0.573	Remote Similarity	NPC196429
0.5667	Remote Similarity	NPC480915
0.5625	Remote Similarity	NPC475556
0.5625	Remote Similarity	NPC311706
0.5604	Remote Similarity	NPC480914
0.5567	Remote Similarity	NPC475629
0.5495	Remote Similarity	NPC5311
0.5481	Remote Similarity	NPC117445
0.5481	Remote Similarity	NPC308262
0.5464	Remote Similarity	NPC240070
0.5385	Remote Similarity	NPC484211
0.534	Remote Similarity	NPC329636
0.5326	Remote Similarity	NPC77299
0.5326	Remote Similarity	NPC34390
0.5326	Remote Similarity	NPC480906
0.5253	Remote Similarity	NPC264336
0.5204	Remote Similarity	NPC62172
0.5181	Remote Similarity	NPC189588
0.5176	Remote Similarity	NPC196471
0.5161	Remote Similarity	NPC484210
0.5152	Remote Similarity	NPC188234
0.5152	Remote Similarity	NPC75616
0.5109	Remote Similarity	NPC471633
0.5102	Remote Similarity	NPC30483
0.5102	Remote Similarity	NPC470897
0.5057	Remote Similarity	NPC475030
0.5052	Remote Similarity	NPC480907
0.5051	Remote Similarity	NPC236973
0.5051	Remote Similarity	NPC27363
0.505	Remote Similarity	NPC125077

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC469752 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6575
0.1-0.2	2470
0.2-0.3	88
0.3-0.4	4
0.4-0.5	5
0.5-0.6	7
0.6-0.7	0
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8077	Intermediate Similarity	NPD7319	Approved
0.5978	Remote Similarity	NPD8296	Phase 4
0.5889	Remote Similarity	NPD7327	Approved
0.5889	Remote Similarity	NPD7328	Phase 4
0.5543	Remote Similarity	NPD8335	Phase 4
0.5484	Remote Similarity	NPD8380	Approved
0.53	Remote Similarity	NPD8378	Pre-clinical
0.53	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