NPASS Compound

Natural Product: NPC27363

Natural Product ID	NPC27363
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Antiaroside E
IUPAC Name	(3S,5R,8R,9S,10R,13R,14S,17R)-14-hydroxy-13-methyl-17-(5-oxo-2H-furan-3-yl)-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-10-carboxylic acid
Synonyms	Antiaroside E
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1169850
PubChem CID	49799050
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 81 86 0 0 0 0 0 0 0 0999 V2000 7.7078 4.2509 1.8084 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6777 3.5128 1.7946 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8516 3.2366 2.8476 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8296 2.3796 2.4153 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0534 2.1108 0.9707 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1319 2.7814 0.6405 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1696 1.2462 0.1660 C 0 0 1 0 0 0 0 0 0 0 0 0 4.5430 1.1332 -1.2822 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6596 -0.3430 -1.5459 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8171 -1.0200 -0.5173 C 0 0 1 0 0 0 0 0 0 0 0 0 4.1136 -0.1813 0.7001 C 0 0 1 0 0 0 0 0 0 0 0 0 5.5069 -0.5173 1.1849 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1687 -0.3704 1.8266 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1619 -1.4953 1.5385 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4457 -1.0677 0.3152 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4064 -1.1945 -0.8552 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8435 -0.2875 -1.9063 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5320 -0.8941 -2.3580 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4042 -1.2710 -1.2734 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2112 -1.8086 -0.0198 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8176 -1.7984 1.0869 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2253 -1.8936 0.5076 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5162 -0.5449 -0.1211 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3833 -0.1461 -1.0095 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7485 -0.5288 -0.7602 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6630 0.3348 -0.2148 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.1147 1.3046 -1.0577 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0790 2.1298 -0.5573 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.5806 3.1482 -1.5373 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2566 1.3870 0.0387 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.8024 0.3803 1.0763 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.7690 -0.5008 0.3956 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.4215 -1.2684 -0.5815 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8636 -0.3888 1.4894 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.1707 2.2612 0.6221 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5532 -3.2439 -0.2639 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3285 -3.8144 -1.3633 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1448 -4.0304 0.7258 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4092 -2.2786 -0.2694 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8721 2.9615 2.4670 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8049 1.4848 3.0389 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6119 2.8388 -0.3202 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1103 1.5967 0.1850 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4957 1.6552 -1.4539 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8039 1.6241 -1.9517 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7283 -0.6183 -1.3331 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4570 -0.6361 -2.5793 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8804 -1.4665 0.7463 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4914 -0.6806 2.2800 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2305 0.3208 1.0206 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6770 -0.6126 2.7935 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5723 0.5553 1.9641 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7811 -2.4072 1.4055 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4836 -1.5779 2.4125 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2105 0.0309 0.4177 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2543 -2.2464 -1.2426 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4768 -0.1851 -2.8007 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5845 0.7028 -1.4502 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7426 -1.7530 -3.0572 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0321 -0.1326 -2.9993 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0447 -2.1123 -1.6809 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6281 -2.5237 1.8784 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7626 -0.7788 1.5501 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3202 -2.7260 -0.2016 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8986 -2.0658 1.3540 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5758 0.1816 0.7160 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8470 0.7752 -0.6404 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8075 0.1463 -1.9981 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1566 0.8379 0.6557 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6222 2.7062 0.2942 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8284 3.4840 -2.2616 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4906 2.7760 -2.0817 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9419 4.0856 -1.0213 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8073 0.8238 -0.7428 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3395 0.9331 1.9157 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3511 -1.2274 1.1191 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5583 -0.6701 -1.3587 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1581 -0.9409 0.7078 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5159 1.8438 1.4489 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7129 -4.8373 0.5158 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1900 -2.8755 -1.0337 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 1 11 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 23 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 28 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 31 34 1 0 30 35 1 0 20 36 1 6 36 37 2 0 36 38 1 0 10 39 1 1 6 2 1 0 11 7 1 0 20 15 1 0 32 26 1 0 16 10 1 0 24 19 1 0 4 40 1 0 4 41 1 0 6 42 1 0 7 43 1 6 8 44 1 0 8 45 1 0 9 46 1 0 9 47 1 0 12 48 1 0 12 49 1 0 12 50 1 0 13 51 1 0 13 52 1 0 14 53 1 0 14 54 1 0 15 55 1 1 16 56 1 6 17 57 1 0 17 58 1 0 18 59 1 0 18 60 1 0 19 61 1 6 21 62 1 0 21 63 1 0 22 64 1 0 22 65 1 0 23 66 1 1 24 67 1 0 24 68 1 0 26 69 1 1 28 70 1 1 29 71 1 0 29 72 1 0 29 73 1 0 30 74 1 6 31 75 1 1 32 76 1 1 33 77 1 0 34 78 1 0 35 79 1 0 38 80 1 0 39 81 1 0 M END

Standard InCHIKey	OKJYWYPYIBXZKZ-FRGJPERLSA-N
Standard InCHI	InChI=1S/C29H42O10/c1-14-22(31)23(32)24(33)25(38-14)39-17-5-9-28(26(34)35)16(12-17)3-4-20-19(28)6-8-27(2)18(7-10-29(20,27)36)15-11-21(30)37-13-15/h11,14,16-20,22-25,31-33,36H,3-10,12-13H2,1-2H3,(H,34,35)/t14-,16+,17-,18+,19-,20+,22-,23+,24+,25+,27+,28+,29-/m0/s1
SMILES	O=C1OCC(=C1)[C@H]1CC[C@]2([C@]1(C)CC[C@H]1[C@H]2CC[C@H]2[C@@]1(CC[C@@H](C2)O[C@H]1O[C@@H](C)[C@@H]([C@H]([C@H]1O)O)O)C(=O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	550.28	Volume:	538.794 ? Van der Waals volume.
Dense:	1.021	LogP:	0.604 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.392 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.559 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	33.0
TPSA:	162.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	5.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.256	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.212	Fsp³:	0.862
MCE-18:	114.074 ? 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:	0.775	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.021 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.136	Promiscuous compounds:	0.148

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.102	MDCK Permeability:	-5.313
Pgp-inhibitor:	0.0	Pgp-substrate:	0.775
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):	0.289
20% Bioavailability (F20%):	0.431	30% Bioavailability (F30%):	0.647
50% Bioavailability (F50%):	0.956

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.014	MRP1:	0.849
Plasma Protein Binding (PPB):	69.61%	Volume Distribution (VD):	-0.476
Fu:	27.862% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.015
BSEP inhibitor:	0.007

ADMET: Metabolism

CYP1A2-inhibitor:	0.006	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.994	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.013
HLM stability:	0.002 ? 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):

1.981

Half-life (T1/2):

3.505

ADMET: Toxicity

hERG Blockers:	0.043	hERG Blockers (10um):	0.116
Human Hepatotoxicity (H-HT):	0.656	Drug-induced Liver Injury (DILI):	0.924
AMES Toxicity:	0.841	Rat Oral Acute Toxicity:	0.943
Maximum Recommended Daily Dose:	0.999	Skin Sensitization:	1.0
Carcinogencity:	0.781	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.991
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.839
Hematotoxicity:	0.897	Drug-induced Nephrotoxicity:	0.993
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.747
A549 Cytotoxicity:	0.394	Hek293 Cytotoxicity:	0.901
BCF:	0.506 ? 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:	3.227 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.754 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.845 ? 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	4
Ratio	2
ED50	10

Activity Type	# Activity
Cell line	7
Non-molecular	9

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[19928902]
NPT308	Cell line	CAKI-1	Homo sapiens	ED50	=	0.13	ug ml-1	DOI[10.6019/CHEMBL1201861]
NPT309	Cell line	1A9	Homo sapiens	ED50	=	0.13	ug ml-1	PMID[19928902]
NPT306	Cell line	PC-3	Homo sapiens	ED50	=	0.16	ug ml-1	PMID[19928902]
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	0.42	ug ml-1	PMID[19928902]
NPT81	Cell line	A549	Homo sapiens	ED50	=	0.07	ug ml-1	PMID[19928902]
NPT91	Cell line	KB	Homo sapiens	ED50	=	0.49	ug ml-1	PMID[17420206]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	0.42	uM	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	1.33	uM	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	264.0	%	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	230.0	%	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.	Ratio	=	7.7	n.a.	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.35	ug ml-1	PMID[24582402]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.73	ug ml-1	PMID[24582402]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.57	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 NPC27363 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	12409
0.1-0.2	31779
0.2-0.3	5220
0.3-0.4	266
0.4-0.5	100
0.5-0.6	55
0.6-0.7	20
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
0.8023	Intermediate Similarity	NPC486151
0.7849	Intermediate Similarity	NPC486140
0.7579	Intermediate Similarity	NPC329784
0.7374	Intermediate Similarity	NPC486152
0.6552	Remote Similarity	NPC99620
0.6404	Remote Similarity	NPC469750
0.6364	Remote Similarity	NPC99728
0.6364	Remote Similarity	NPC87250
0.6364	Remote Similarity	NPC244402
0.6364	Remote Similarity	NPC50305
0.6333	Remote Similarity	NPC76572
0.6333	Remote Similarity	NPC193382
0.6146	Remote Similarity	NPC471357
0.6146	Remote Similarity	NPC469757
0.6146	Remote Similarity	NPC117702
0.6111	Remote Similarity	NPC196429
0.6044	Remote Similarity	NPC157376
0.6044	Remote Similarity	NPC17896
0.6044	Remote Similarity	NPC469755
0.6044	Remote Similarity	NPC284406
0.6044	Remote Similarity	NPC197707
0.6044	Remote Similarity	NPC251866
0.6044	Remote Similarity	NPC142066
0.6044	Remote Similarity	NPC603972
0.5934	Remote Similarity	NPC309034
0.587	Remote Similarity	NPC5311
0.587	Remote Similarity	NPC480915
0.5816	Remote Similarity	NPC240070
0.5699	Remote Similarity	NPC77299
0.5699	Remote Similarity	NPC480906
0.5638	Remote Similarity	NPC480914
0.5591	Remote Similarity	NPC84987
0.5455	Remote Similarity	NPC30483
0.5455	Remote Similarity	NPC470897
0.5408	Remote Similarity	NPC480907
0.54	Remote Similarity	NPC236973
0.5361	Remote Similarity	NPC179412
0.5361	Remote Similarity	NPC471356
0.5361	Remote Similarity	NPC471353
0.5347	Remote Similarity	NPC480910
0.5347	Remote Similarity	NPC480909
0.5319	Remote Similarity	NPC471633
0.5312	Remote Similarity	NPC199428
0.5312	Remote Similarity	NPC109448
0.5312	Remote Similarity	NPC310341
0.5263	Remote Similarity	NPC486129
0.5258	Remote Similarity	NPC77319
0.5258	Remote Similarity	NPC471351
0.5258	Remote Similarity	NPC83287
0.5258	Remote Similarity	NPC471355
0.5248	Remote Similarity	NPC32177
0.5248	Remote Similarity	NPC292467
0.5248	Remote Similarity	NPC469756
0.5248	Remote Similarity	NPC275901
0.5243	Remote Similarity	NPC486143
0.5243	Remote Similarity	NPC486142
0.5243	Remote Similarity	NPC486149
0.5213	Remote Similarity	NPC158344
0.5208	Remote Similarity	NPC486126
0.5196	Remote Similarity	NPC188234
0.5196	Remote Similarity	NPC486130
0.5192	Remote Similarity	NPC469749
0.5146	Remote Similarity	NPC486127
0.5102	Remote Similarity	NPC250556
0.51	Remote Similarity	NPC72260
0.5096	Remote Similarity	NPC486135
0.5096	Remote Similarity	NPC486137
0.5053	Remote Similarity	NPC474418
0.5051	Remote Similarity	NPC9499
0.5051	Remote Similarity	NPC471360
0.5051	Remote Similarity	NPC469751
0.5051	Remote Similarity	NPC471361
0.5051	Remote Similarity	NPC86159
0.5051	Remote Similarity	NPC469752
0.5051	Remote Similarity	NPC469754
0.5051	Remote Similarity	NPC70542
0.5051	Remote Similarity	NPC305574
0.5048	Remote Similarity	NPC232785
0.5048	Remote Similarity	NPC486139

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC27363 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4627
0.1-0.2	4397
0.2-0.3	110
0.3-0.4	7
0.4-0.5	4
0.5-0.6	4
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
0.6044	Remote Similarity	NPD7319	Approved
0.5258	Remote Similarity	NPD7327	Approved
0.5258	Remote Similarity	NPD7328	Phase 4
0.5102	Remote Similarity	NPD7507	Pre-clinical
0.51	Remote Similarity	NPD8294	Phase 4

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