NPASS Compound

Natural Product: NPC99728

Natural Product ID	NPC99728
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Periplorhamnoside
IUPAC Name	3-[(3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-3-[(2S,3R,4R,5R,6S)-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]phenanthren-17-yl]-2H-furan-5-one
Synonyms	Periplorhamnoside
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1169855
PubChem CID	49799055
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 10.0377 -0.4419 -1.4618 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8356 -0.0738 -1.2291 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1995 0.8454 -2.0357 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9051 1.0265 -1.5107 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7871 0.1665 -0.3364 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9354 -0.4732 -0.1885 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6095 0.0199 0.5755 C 0 0 1 0 0 0 0 0 0 0 0 0 5.2606 1.3885 1.1782 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7494 1.3587 1.1535 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4872 0.7157 -0.1797 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3803 -0.4980 -0.0939 C 0 0 1 0 0 0 0 0 0 0 0 0 4.5681 -1.0626 -1.4578 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8063 -1.5626 0.8064 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3667 -1.8870 0.5285 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5528 -0.6359 0.6550 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0764 0.3051 -0.4091 C 0 0 1 0 0 0 0 0 0 0 0 0 1.1337 1.4325 -0.6338 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0715 0.8376 -1.3679 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4013 -0.5449 -0.8845 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0682 -0.8492 0.4949 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1650 -2.3510 0.7239 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7107 -0.1493 1.5786 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8376 0.6805 1.1188 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6505 0.1400 -0.0048 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9015 -0.7079 -0.9771 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7915 -0.4877 0.4931 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9605 0.1377 0.1570 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.7170 -0.7462 -0.6101 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8428 -0.1948 -1.1484 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.7171 -1.3556 -1.6476 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6803 0.6109 -0.2206 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.9309 1.4071 0.7908 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.8143 0.5282 1.3408 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.3932 -0.6419 1.8359 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7923 1.8278 1.7828 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.4452 1.4972 -0.9954 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1377 -1.5377 -1.7351 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8730 1.5782 -1.1776 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8361 2.1121 -1.2700 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2118 0.7654 -2.3555 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1547 -1.1829 0.5940 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9157 -0.5948 1.4653 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5936 2.1739 0.4426 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6880 1.5325 2.1696 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4446 0.7398 2.0186 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3383 2.3869 1.2233 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9434 -2.0031 -1.5316 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6000 -1.4248 -1.6573 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1540 -0.4179 -2.2630 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3963 -2.4862 0.6360 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9080 -1.2918 1.8636 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0788 -2.6794 1.2506 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2336 -2.3253 -0.4823 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7065 -0.2492 1.6858 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0831 -0.3054 -1.3609 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8318 1.9649 0.2898 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6388 2.1683 -1.3241 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2867 0.7172 -2.4335 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9169 1.5227 -1.4140 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1237 -2.5206 1.7973 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3685 -2.9753 0.0150 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2486 -2.5984 0.6867 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0705 -0.8411 2.3770 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0202 0.5277 2.1112 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5346 0.8290 1.9976 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4728 1.7301 0.9097 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0389 1.0365 -0.5759 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2123 -1.7879 -0.9136 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1635 -0.4292 -2.0419 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7991 1.0581 -0.4685 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6361 0.4106 -2.0755 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2988 -1.8398 -2.5289 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7843 -2.0478 -0.7572 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7537 -0.9850 -1.8023 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4164 -0.0308 0.3315 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4179 2.2627 0.2739 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2855 1.1105 2.0952 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5418 -0.6116 2.8025 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9855 2.8024 1.6593 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8825 2.1155 -0.3301 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1664 -1.1524 -2.6542 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7896 2.5109 -0.8316 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 6 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 1 20 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 24 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 29 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 32 35 1 0 31 36 1 0 19 37 1 6 10 38 1 6 6 2 1 0 11 7 1 0 20 15 1 0 33 27 1 0 16 10 1 0 25 19 1 0 4 39 1 0 4 40 1 0 6 41 1 0 7 42 1 1 8 43 1 0 8 44 1 0 9 45 1 0 9 46 1 0 12 47 1 0 12 48 1 0 12 49 1 0 13 50 1 0 13 51 1 0 14 52 1 0 14 53 1 0 15 54 1 1 16 55 1 6 17 56 1 0 17 57 1 0 18 58 1 0 18 59 1 0 21 60 1 0 21 61 1 0 21 62 1 0 22 63 1 0 22 64 1 0 23 65 1 0 23 66 1 0 24 67 1 6 25 68 1 0 25 69 1 0 27 70 1 6 29 71 1 6 30 72 1 0 30 73 1 0 30 74 1 0 31 75 1 1 32 76 1 6 33 77 1 1 34 78 1 0 35 79 1 0 36 80 1 0 37 81 1 0 38 82 1 0 M END

Standard InCHIKey	RAWRNCRYFFPACC-CSOOXTHUSA-N
Standard InCHI	InChI=1S/C29H44O9/c1-15-22(31)23(32)24(33)25(37-15)38-17-4-8-26(2)19-5-9-27(3)18(16-12-21(30)36-14-16)7-11-29(27,35)20(19)6-10-28(26,34)13-17/h12,15,17-20,22-25,31-35H,4-11,13-14H2,1-3H3/t15-,17-,18+,19-,20+,22-,23+,24+,25+,26+,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@]2([C@]1(C)CC[C@@H](C2)O[C@H]1O[C@@H](C)[C@@H]([C@H]([C@H]1O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	536.3	Volume:	532.64 ? Van der Waals volume.
Dense:	1.007	LogP:	1.041 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.661 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.479 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	32.0
TPSA:	145.91 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	5.0	Rings:	6.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.268	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.173	Fsp³:	0.897
MCE-18:	116.291 ? 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:	0.76	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.02 ? 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:	0.146	Promiscuous compounds:	0.349

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.422	MDCK Permeability:	-5.258
Pgp-inhibitor:	0.0	Pgp-substrate:	0.993
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):	0.111
20% Bioavailability (F20%):	0.751	30% Bioavailability (F30%):	0.653
50% Bioavailability (F50%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.367	MRP1:	0.835
Plasma Protein Binding (PPB):	75.642%	Volume Distribution (VD):	-0.435
Fu:	22.172% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.129
BSEP inhibitor:	0.009

ADMET: Metabolism

CYP1A2-inhibitor:	0.999	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.288	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.004	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.327
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.494
HLM stability:	0.041 ? 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):

2.401

Half-life (T1/2):

3.235

ADMET: Toxicity

hERG Blockers:	0.171	hERG Blockers (10um):	0.666
Human Hepatotoxicity (H-HT):	0.783	Drug-induced Liver Injury (DILI):	0.534
AMES Toxicity:	0.882	Rat Oral Acute Toxicity:	0.971
Maximum Recommended Daily Dose:	1.0	Skin Sensitization:	1.0
Carcinogencity:	0.926	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.993
Drug-induced Neurotoxicity:	0.007	Ototoxicity:	0.68
Hematotoxicity:	0.525	Drug-induced Nephrotoxicity:	0.974
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.85
A549 Cytotoxicity:	0.934	Hek293 Cytotoxicity:	0.994
BCF:	0.698 ? 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:	3.224 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.466 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.895 ? 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	=	0.017	ug ml-1	PMID[11312774]
NPT308	Cell line	CAKI-1	Homo sapiens	ED50	=	0.014	ug ml-1	PMID[23403082]
NPT309	Cell line	1A9	Homo sapiens	ED50	=	0.012	ug ml-1	PMID[23403082]
NPT306	Cell line	PC-3	Homo sapiens	ED50	=	0.021	ug ml-1	PMID[22500574]
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	0.018	ug ml-1	PMID[22500574]
NPT81	Cell line	A549	Homo sapiens	ED50	=	0.012	ug ml-1	PMID[22500574]
NPT91	Cell line	KB	Homo sapiens	ED50	=	0.054	ug ml-1	PMID[18278869]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	0.05	uM	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	0.25	uM	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	381.0	%	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	355.0	%	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Ratio	=	11.0	n.a.	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Ratio	=	8.8	n.a.	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.044	ug ml-1	PMID[24582402]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.082	ug ml-1	PMID[24582402]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.02	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 NPC99728 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	15208
0.1-0.2	28956
0.2-0.3	5142
0.3-0.4	334
0.4-0.5	70
0.5-0.6	70
0.6-0.7	32
0.7-0.8	0
0.8-0.85	4
0.85-0.9	9
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC87250
1.0	High Similarity	NPC244402
1.0	High Similarity	NPC50305
0.875	High Similarity	NPC84987
0.863	High Similarity	NPC157376
0.863	High Similarity	NPC17896
0.863	High Similarity	NPC469755
0.863	High Similarity	NPC284406
0.863	High Similarity	NPC197707
0.863	High Similarity	NPC251866
0.863	High Similarity	NPC142066
0.863	High Similarity	NPC603972
0.8219	Intermediate Similarity	NPC158344
0.8158	Intermediate Similarity	NPC77319
0.8158	Intermediate Similarity	NPC471351
0.8158	Intermediate Similarity	NPC471355
0.7973	Intermediate Similarity	NPC474418
0.7632	Intermediate Similarity	NPC99620
0.759	Intermediate Similarity	NPC475629
0.747	Intermediate Similarity	NPC475556
0.747	Intermediate Similarity	NPC311706
0.7436	Intermediate Similarity	NPC469750
0.7342	Intermediate Similarity	NPC76572
0.7342	Intermediate Similarity	NPC193382
0.7308	Intermediate Similarity	NPC309034
0.7215	Intermediate Similarity	NPC34390
0.716	Intermediate Similarity	NPC9499
0.716	Intermediate Similarity	NPC471360
0.716	Intermediate Similarity	NPC469751
0.716	Intermediate Similarity	NPC471361
0.716	Intermediate Similarity	NPC86159
0.716	Intermediate Similarity	NPC469752
0.716	Intermediate Similarity	NPC469754
0.716	Intermediate Similarity	NPC70542
0.7089	Intermediate Similarity	NPC219085
0.7073	Intermediate Similarity	NPC471354
0.7073	Intermediate Similarity	NPC27507
0.7011	Intermediate Similarity	NPC469749
0.6875	Remote Similarity	NPC196429
0.686	Remote Similarity	NPC32793
0.686	Remote Similarity	NPC116075
0.679	Remote Similarity	NPC5311
0.6667	Remote Similarity	NPC240070
0.6627	Remote Similarity	NPC83287
0.6585	Remote Similarity	NPC77299
0.6585	Remote Similarity	NPC480906
0.6585	Remote Similarity	NPC480915
0.6506	Remote Similarity	NPC10823
0.6506	Remote Similarity	NPC480914
0.6374	Remote Similarity	NPC146857
0.6374	Remote Similarity	NPC247190
0.6364	Remote Similarity	NPC27363
0.625	Remote Similarity	NPC30483
0.625	Remote Similarity	NPC470897
0.6235	Remote Similarity	NPC180079
0.6207	Remote Similarity	NPC480907
0.619	Remote Similarity	NPC6108
0.619	Remote Similarity	NPC89514
0.618	Remote Similarity	NPC236973
0.6163	Remote Similarity	NPC179412
0.6163	Remote Similarity	NPC471356
0.6163	Remote Similarity	NPC471353
0.6145	Remote Similarity	NPC471633
0.6111	Remote Similarity	NPC608063
0.6081	Remote Similarity	NPC97487
0.6044	Remote Similarity	NPC264336
0.6	Remote Similarity	NPC32177
0.6	Remote Similarity	NPC292467
0.6	Remote Similarity	NPC469756
0.6	Remote Similarity	NPC275901
0.5978	Remote Similarity	NPC59288
0.5978	Remote Similarity	NPC486143
0.5978	Remote Similarity	NPC486142
0.5978	Remote Similarity	NPC486149
0.5934	Remote Similarity	NPC188234
0.5934	Remote Similarity	NPC480910
0.5934	Remote Similarity	NPC480909
0.593	Remote Similarity	NPC199428
0.593	Remote Similarity	NPC243196
0.593	Remote Similarity	NPC109448
0.593	Remote Similarity	NPC310341
0.5918	Remote Similarity	NPC329675
0.5918	Remote Similarity	NPC194716
0.5862	Remote Similarity	NPC146456
0.5844	Remote Similarity	NPC72772
0.5843	Remote Similarity	NPC72260
0.5806	Remote Similarity	NPC486135
0.5806	Remote Similarity	NPC486137
0.5745	Remote Similarity	NPC232785
0.5745	Remote Similarity	NPC486139
0.5684	Remote Similarity	NPC486146
0.5682	Remote Similarity	NPC250556
0.5638	Remote Similarity	NPC125077
0.5618	Remote Similarity	NPC471359
0.5618	Remote Similarity	NPC305574
0.5612	Remote Similarity	NPC486144
0.5612	Remote Similarity	NPC486145
0.5612	Remote Similarity	NPC486147
0.5612	Remote Similarity	NPC486148
0.5568	Remote Similarity	NPC84949
0.5568	Remote Similarity	NPC480562
0.5568	Remote Similarity	NPC74945
0.5568	Remote Similarity	NPC31354
0.5568	Remote Similarity	NPC69576
0.5521	Remote Similarity	NPC329986
0.5521	Remote Similarity	NPC140092
0.5517	Remote Similarity	NPC484211
0.5513	Remote Similarity	NPC10232
0.5464	Remote Similarity	NPC486138
0.5464	Remote Similarity	NPC276838
0.5455	Remote Similarity	NPC329636
0.5455	Remote Similarity	NPC475590
0.5455	Remote Similarity	NPC486136
0.5444	Remote Similarity	NPC93883
0.5426	Remote Similarity	NPC471357
0.5426	Remote Similarity	NPC469757
0.5426	Remote Similarity	NPC117702
0.5426	Remote Similarity	NPC486130
0.5402	Remote Similarity	NPC473852
0.5393	Remote Similarity	NPC604978
0.5385	Remote Similarity	NPC469753
0.5368	Remote Similarity	NPC486127
0.5368	Remote Similarity	NPC610296
0.5347	Remote Similarity	NPC120390
0.5347	Remote Similarity	NPC74259
0.5347	Remote Similarity	NPC475419
0.5341	Remote Similarity	NPC486129
0.5294	Remote Similarity	NPC474908
0.5294	Remote Similarity	NPC486134
0.5294	Remote Similarity	NPC486141
0.5281	Remote Similarity	NPC486126
0.5275	Remote Similarity	NPC483822
0.5275	Remote Similarity	NPC484202
0.5189	Remote Similarity	NPC286809
0.5155	Remote Similarity	NPC55532
0.5143	Remote Similarity	NPC474423
0.51	Remote Similarity	NPC486132
0.51	Remote Similarity	NPC486131
0.5096	Remote Similarity	NPC486150
0.505	Remote Similarity	NPC486128

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC99728 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6034
0.1-0.2	2970
0.2-0.3	128
0.3-0.4	4
0.4-0.5	7
0.5-0.6	4
0.6-0.7	2
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.863	High Similarity	NPD7319	Approved
0.6627	Remote Similarity	NPD7327	Approved
0.6627	Remote Similarity	NPD7328	Phase 4
0.5843	Remote Similarity	NPD8294	Phase 4
0.5682	Remote Similarity	NPD7507	Pre-clinical
0.5275	Remote Similarity	NPD7516	Pre-clinical
0.5155	Remote Similarity	NPD8377	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