NPASS Compound

Natural Product: NPC469753

Natural Product ID	NPC469753
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Toxicarioside B
IUPAC Name	(3S,5S,8R,9S,10S,12R,13S,14S,17R)-3-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-3-methoxy-6-methyloxan-2-yl]oxy-5,12,14-trihydroxy-13-methyl-17-(5-oxo-2H-furan-3-yl)-2,3,4,6,7,8,9,11,12,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-10-carbaldehyde
Synonyms	Toxicarioside B
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1169682
PubChem CID	49799520
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 85 90 0 0 0 0 0 0 0 0999 V2000 5.9684 1.6214 2.6958 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9581 2.1247 1.2708 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1565 1.6134 0.5134 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6179 0.9667 -0.7630 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6141 -0.0896 -0.2793 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4314 0.6517 0.3151 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7619 1.9409 0.6345 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4468 0.6853 -0.6516 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2710 0.0649 -0.3026 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1884 1.1503 -0.3169 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4146 1.1234 -1.6042 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3444 -0.1576 -1.8518 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8209 -0.0567 -1.6132 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2949 1.2275 -1.0413 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6140 1.2732 -0.4202 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4075 0.0434 -0.2584 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6659 -0.2847 1.2019 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1856 -1.7082 1.0939 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3025 -2.3552 0.0660 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7418 -1.2234 -0.7288 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2727 -1.2315 -0.7473 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5295 -1.1663 0.5169 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0951 -1.6207 0.2111 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3391 -1.2933 -1.1688 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8481 -1.0081 -1.2467 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2321 -2.4901 -1.9273 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1513 -1.4289 -2.0684 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7023 0.5182 1.8522 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3779 1.5889 1.5222 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3195 1.9923 2.5584 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1149 2.9888 2.5331 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1842 1.0829 3.5789 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2218 0.1573 3.2246 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7498 0.1248 -0.9500 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5506 1.8986 0.8571 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1858 -0.4167 -3.3187 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3413 -1.4084 -3.7669 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2461 -0.8970 0.6365 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3330 -2.1764 0.1315 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6297 0.3549 -1.4917 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8311 0.6120 1.2085 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6511 0.7495 2.8009 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9790 1.3635 3.0738 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3832 2.3902 3.4107 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1033 3.2439 1.3457 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8972 2.3992 0.2746 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1028 1.7721 -1.3116 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3349 -0.6586 -1.1834 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1292 0.1258 1.2378 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3800 -0.3454 0.7216 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6248 1.0709 0.6009 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6611 2.1786 -0.2898 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2272 1.2489 -2.3909 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1649 2.0413 -1.6970 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4329 -0.1982 -2.5597 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5321 1.5670 -0.2813 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1862 1.9977 -1.8661 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2500 2.0094 -1.0046 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7068 -0.2822 1.7810 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1661 -2.2303 2.0706 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2139 -1.6563 0.7025 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5487 -2.9943 0.5418 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9518 -3.0457 -0.5395 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9772 -2.1908 -1.2690 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4167 -0.1426 0.9426 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9103 -1.7943 1.3466 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5798 -1.2752 1.0236 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1273 -2.7412 0.3711 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3657 -1.9751 -1.0424 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0117 -0.6552 -2.2863 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6174 -3.1964 -1.3407 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0866 -2.3837 -2.2232 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2675 2.1268 0.6156 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4202 0.1507 3.9694 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6509 -0.8849 3.1582 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8382 1.1188 -1.4825 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8444 -0.6150 -1.7739 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6222 0.0077 -0.3224 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4746 2.8702 0.7769 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5521 0.3030 -4.0526 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8409 -2.8065 0.8766 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8665 -2.2404 -0.8230 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2949 -2.5446 -0.0496 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7189 0.7359 -2.4107 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7751 0.5932 0.8801 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 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 24 26 1 0 20 27 1 0 17 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 30 32 1 0 32 33 1 0 16 34 1 0 15 35 1 0 12 36 1 0 36 37 2 0 5 38 1 0 38 39 1 0 4 40 1 0 3 41 1 0 7 2 1 0 25 9 1 0 24 12 1 0 21 13 1 0 20 16 1 0 33 28 1 0 1 42 1 0 1 43 1 0 1 44 1 0 2 45 1 0 3 46 1 0 4 47 1 0 5 48 1 0 6 49 1 0 9 50 1 0 10 51 1 0 10 52 1 0 11 53 1 0 11 54 1 0 13 55 1 0 14 56 1 0 14 57 1 0 15 58 1 0 17 59 1 0 18 60 1 0 18 61 1 0 19 62 1 0 19 63 1 0 21 64 1 0 22 65 1 0 22 66 1 0 23 67 1 0 23 68 1 0 25 69 1 0 25 70 1 0 26 71 1 0 27 72 1 0 29 73 1 0 33 74 1 0 33 75 1 0 34 76 1 0 34 77 1 0 34 78 1 0 35 79 1 0 36 80 1 0 39 81 1 0 39 82 1 0 39 83 1 0 40 84 1 0 41 85 1 0 M END

Standard InCHIKey	WUAYGHQTMPWDRU-VPRBOWIESA-N
Standard InCHI	InChI=1S/C30H44O11/c1-15-23(34)24(35)25(38-3)26(40-15)41-17-4-7-28(14-31)20-11-21(32)27(2)18(16-10-22(33)39-13-16)6-9-30(27,37)19(20)5-8-29(28,36)12-17/h10,14-15,17-21,23-26,32,34-37H,4-9,11-13H2,1-3H3/t15-,17+,18-,19-,20+,21-,23-,24+,25-,26-,27+,28+,29+,30+/m1/s1
SMILES	CC1C(C(C(C(O1)OC2CCC3(C4CC(C5(C(CCC5(C4CCC3(C2)O)O)C6=CC(=O)OC6)C)O)C=O)OC)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	580.29	Volume:	564.88 ? Van der Waals volume.
Dense:	1.027	LogP:	-0.804 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.06 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.923 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	33.0
TPSA:	172.21 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	5.0	Rings:	6.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.173	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.562	Fsp³:	0.867
MCE-18:	118.5 ? 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:	0.009	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.013 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.125 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.104	Promiscuous compounds:	0.003

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.774	MDCK Permeability:	-5.151
Pgp-inhibitor:	0.0	Pgp-substrate:	0.992
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):	0.998
20% Bioavailability (F20%):	0.911	30% Bioavailability (F30%):	0.969
50% Bioavailability (F50%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.903
Plasma Protein Binding (PPB):	29.193%	Volume Distribution (VD):	-0.472
Fu:	76.431% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.002
OATP1B3 inhibitor:	0.622	BCRP inhibitor:	0.001
BSEP inhibitor:	0.014

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.669	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.001
HLM stability:	0.0 ? 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):

3.061

Half-life (T1/2):

5.271

ADMET: Toxicity

hERG Blockers:	0.231	hERG Blockers (10um):	0.472
Human Hepatotoxicity (H-HT):	0.761	Drug-induced Liver Injury (DILI):	0.109
AMES Toxicity:	0.938	Rat Oral Acute Toxicity:	0.961
Maximum Recommended Daily Dose:	0.994	Skin Sensitization:	0.754
Carcinogencity:	0.734	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.532
Drug-induced Neurotoxicity:	0.236	Ototoxicity:	0.985
Hematotoxicity:	0.201	Drug-induced Nephrotoxicity:	0.346
Genotoxicity:	0.998	RPMI-8226 Immunitoxicity:	0.607
A549 Cytotoxicity:	0.238	Hek293 Cytotoxicity:	0.917
BCF:	0.473 ? 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:	3.355 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.325 ? 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
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	DOI[10.6019/CHEMBL1201861]
NPT308	Cell line	CAKI-1	Homo sapiens	ED50	=	0.07	ug ml-1	PubChem BioAssay data set
NPT309	Cell line	1A9	Homo sapiens	ED50	=	0.063	ug ml-1	DOI[10.6019/CHEMBL1201861]
NPT306	Cell line	PC-3	Homo sapiens	ED50	=	0.091	ug ml-1	PubChem BioAssay data set
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	0.092	ug ml-1	PubChem BioAssay data set
NPT81	Cell line	A549	Homo sapiens	ED50	=	0.058	ug ml-1	PubChem BioAssay data set
NPT91	Cell line	KB	Homo sapiens	ED50	=	0.13	ug ml-1	PMID[16643036]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	0.1	uM	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	163.0	%	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Ratio	=	10.0	n.a.	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	71.4	%	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	=	0.13	ug ml-1	PMID[24582402]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.14	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 NPC469753 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	15776
0.1-0.2	29921
0.2-0.3	3888
0.3-0.4	133
0.4-0.5	85
0.5-0.6	27
0.6-0.7	14
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	Natural Product ID
0.8101	Intermediate Similarity	NPC10823
0.7683	Intermediate Similarity	NPC9499
0.7683	Intermediate Similarity	NPC471360
0.7683	Intermediate Similarity	NPC469751
0.7683	Intermediate Similarity	NPC471361
0.7683	Intermediate Similarity	NPC86159
0.7683	Intermediate Similarity	NPC469752
0.7683	Intermediate Similarity	NPC469754
0.7683	Intermediate Similarity	NPC70542
0.7059	Intermediate Similarity	NPC471359
0.6706	Remote Similarity	NPC6108
0.6706	Remote Similarity	NPC89514
0.6552	Remote Similarity	NPC77319
0.6552	Remote Similarity	NPC471351
0.6552	Remote Similarity	NPC471355
0.6404	Remote Similarity	NPC471354
0.6404	Remote Similarity	NPC27507
0.6329	Remote Similarity	NPC469794
0.618	Remote Similarity	NPC180079
0.6136	Remote Similarity	NPC17896
0.6136	Remote Similarity	NPC469755
0.6136	Remote Similarity	NPC284406
0.6136	Remote Similarity	NPC197707
0.6136	Remote Similarity	NPC251866
0.5934	Remote Similarity	NPC179412
0.5934	Remote Similarity	NPC471356
0.5667	Remote Similarity	NPC219085
0.5657	Remote Similarity	NPC247190
0.5618	Remote Similarity	NPC474418
0.5591	Remote Similarity	NPC471353
0.55	Remote Similarity	NPC146857
0.5435	Remote Similarity	NPC34390
0.5417	Remote Similarity	NPC173555
0.5385	Remote Similarity	NPC99728
0.5385	Remote Similarity	NPC87250
0.5385	Remote Similarity	NPC244402
0.5385	Remote Similarity	NPC50305
0.5288	Remote Similarity	NPC329636
0.5269	Remote Similarity	NPC157376
0.5269	Remote Similarity	NPC142066
0.5269	Remote Similarity	NPC603972
0.5253	Remote Similarity	NPC32793
0.5253	Remote Similarity	NPC116075
0.5253	Remote Similarity	NPC608063
0.5248	Remote Similarity	NPC469749
0.5172	Remote Similarity	NPC475030
0.5161	Remote Similarity	NPC484211
0.514	Remote Similarity	NPC329675
0.514	Remote Similarity	NPC194716
0.5119	Remote Similarity	NPC189588
0.5104	Remote Similarity	NPC93883

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC469753 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6312
0.1-0.2	2765
0.2-0.3	59
0.3-0.4	3
0.4-0.5	7
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
0.6136	Remote Similarity	NPD7319	Approved
0.5484	Remote Similarity	NPD8335	Phase 4
0.5417	Remote Similarity	NPD8296	Phase 4
0.5104	Remote Similarity	NPD8380	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