NPASS Compound

Natural Product: NPC470494

Natural Product ID	NPC470494
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	XCXYVTYOGSYQQL-ZKIGBFCOSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2047418
PubChem CID	66572355
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001560] Withanolides 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 93 98 0 0 0 0 0 0 0 0999 V2000 0.0500 -0.8588 -0.8857 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1646 0.6182 -0.7897 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3172 0.9456 0.0738 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5386 2.4485 0.2215 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0167 2.6702 0.4251 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5030 1.2769 0.6368 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6801 0.5632 -0.4528 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9759 1.2297 -1.7800 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0089 -0.8758 -0.4937 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5195 -0.9540 -0.8273 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2216 -0.4093 0.4011 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.9522 1.0701 0.5602 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.5434 1.4501 1.9227 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0161 1.2120 1.9000 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.5255 0.1012 1.2255 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.6558 -0.7675 0.3971 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.1809 -0.7634 -1.0446 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7856 -2.1819 0.8623 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8043 -2.9867 0.8596 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.0559 -2.7073 1.3448 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0131 -1.8643 1.6134 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8896 -0.4171 1.4595 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.8186 -0.0007 0.4906 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6048 1.4524 0.6130 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0707 1.4310 -0.5695 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8484 1.1628 0.6376 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0853 0.3841 0.5277 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6920 0.0893 -0.6023 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0432 0.5993 -1.8102 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5924 0.3395 -2.9180 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8711 1.3376 -1.7226 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9385 -0.7000 -0.6407 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9902 0.0046 -1.2218 O 0 0 0 0 0 0 0 0 0 0 0 0 7.4312 -0.8794 -1.2697 Si 0 0 0 0 0 4 0 0 0 0 0 0 8.7800 -0.1137 -0.2461 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6561 -0.4775 1.2151 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7296 1.3966 -0.3427 C 0 0 0 0 0 0 0 0 0 0 0 0 10.1279 -0.5977 -0.7377 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2099 -2.6461 -0.7188 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0288 -0.9221 -3.0487 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7178 -0.1190 1.7784 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2557 -1.3127 -1.8516 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5475 -1.3496 -0.0941 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1057 -1.1485 -0.6336 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4959 0.9211 -1.8380 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2452 0.5396 1.0985 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2356 3.0201 -0.6577 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0385 2.7838 1.1654 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4870 3.1912 -0.4335 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2370 3.2864 1.3177 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1270 0.9286 1.6187 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2295 1.9651 -2.0878 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0068 0.4502 -2.5769 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9761 1.7082 -1.7451 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5323 -1.3533 -1.3617 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8264 -1.3844 0.4750 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8372 -1.9744 -1.0112 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6822 -0.3378 -1.7204 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7378 -0.9110 1.2792 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4834 1.6761 -0.1985 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0965 0.7010 2.6387 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2285 2.4363 2.2572 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5547 1.6392 2.7737 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2704 -0.8942 -1.0136 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7762 -1.6696 -1.5627 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8523 0.1376 -1.5914 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1716 -3.7952 1.4685 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9519 -2.2614 1.9707 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2658 0.0444 2.4203 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4853 0.8526 0.1211 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7246 2.4960 -0.5493 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2736 0.7199 1.4851 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1798 2.1623 1.0712 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2641 -1.0054 0.3737 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8318 -1.6382 -1.2317 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7943 -1.1350 1.4284 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5717 -1.0183 1.5798 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5890 0.4286 1.8728 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4945 1.7552 -1.3521 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0809 1.8150 0.4429 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7690 1.7591 -0.0931 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4111 -0.1365 -1.7051 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0938 -1.6996 -0.8604 H 0 0 0 0 0 0 0 0 0 0 0 0 10.9098 -0.3472 -0.0039 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7745 -3.2863 -1.5163 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1874 -3.0930 -0.4471 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5448 -2.7011 0.1687 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5032 0.0320 -3.3408 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6894 -1.8011 -3.1551 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1123 -1.0931 -3.6695 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1598 0.2059 2.6886 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7727 -1.2154 1.8211 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7252 0.3666 1.8703 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 7 8 1 6 7 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 6 16 18 1 0 18 19 2 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 15 24 1 6 2 25 1 0 25 26 1 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 29 31 1 0 28 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 35 37 1 0 35 38 1 0 34 39 1 0 34 40 1 0 27 41 1 0 7 3 1 0 16 11 1 0 31 25 1 0 12 6 1 0 24 14 1 0 22 15 1 0 1 42 1 0 1 43 1 0 1 44 1 0 2 45 1 6 3 46 1 1 4 47 1 0 4 48 1 0 5 49 1 0 5 50 1 0 6 51 1 1 8 52 1 0 8 53 1 0 8 54 1 0 9 55 1 0 9 56 1 0 10 57 1 0 10 58 1 0 11 59 1 1 12 60 1 6 13 61 1 0 13 62 1 0 14 63 1 1 17 64 1 0 17 65 1 0 17 66 1 0 20 67 1 0 21 68 1 0 22 69 1 1 23 70 1 0 25 71 1 1 26 72 1 0 26 73 1 0 32 74 1 0 32 75 1 0 36 76 1 0 36 77 1 0 36 78 1 0 37 79 1 0 37 80 1 0 37 81 1 0 38 82 1 0 38 83 1 0 38 84 1 0 39 85 1 0 39 86 1 0 39 87 1 0 40 88 1 0 40 89 1 0 40 90 1 0 41 91 1 0 41 92 1 0 41 93 1 0 M END

Standard InCHIKey	XCXYVTYOGSYQQL-ZKIGBFCOSA-N
Standard InCHI	InChI=1S/C34H52O6Si/c1-19-16-26(39-30(37)22(19)18-38-41(8,9)31(3,4)5)20(2)23-10-11-24-21-17-29-34(40-29)28(36)13-12-27(35)33(34,7)25(21)14-15-32(23,24)6/h12-13,20-21,23-26,28-29,36H,10-11,14-18H2,1-9H3/t20-,21-,23+,24-,25-,26+,28-,29+,32+,33-,34+/m0/s1
SMILES	C[C@@H]([C@H]1CC[C@@H]2[C@]1(C)CC[C@H]1[C@H]2C[C@@H]2[C@]3([C@]1(C)C(=O)C=C[C@@H]3O)O2)[C@H]1CC(=C(C(=O)O1)CO[Si](C(C)(C)C)(C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	584.35	Volume:	38792970.28 ? Van der Waals volume.
Dense:	0.0	LogP:	4.83 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.228 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.09 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	30.0
TPSA:	85.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	6.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.229	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.853	Fsp³:	0.824
MCE-18:	158.226 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.746	Fluc inhibitor:	0.06 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? 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:	0.099	Promiscuous compounds:	0.115

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.252	MDCK Permeability:	-4.984
Pgp-inhibitor:	0.287	Pgp-substrate:	0.005
PAMPA:	0.012 ? 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%):	0.012	30% Bioavailability (F30%):	0.213
50% Bioavailability (F50%):	0.94

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.086
Plasma Protein Binding (PPB):	91.479%	Volume Distribution (VD):	0.067
Fu:	7.845% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.003
BSEP inhibitor:	0.922

ADMET: Metabolism

CYP1A2-inhibitor:	0.138	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.004	CYP2C9-substrate:	0.03
CYP2D6-inhibitor:	0.177	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.941	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

9.035

Half-life (T1/2):

1.11

ADMET: Toxicity

hERG Blockers:	0.069	hERG Blockers (10um):	0.317
Human Hepatotoxicity (H-HT):	0.144	Drug-induced Liver Injury (DILI):	0.17
AMES Toxicity:	0.031	Rat Oral Acute Toxicity:	0.079
Maximum Recommended Daily Dose:	0.473	Skin Sensitization:	1.0
Carcinogencity:	0.954	Eye Corrosion:	0.855
Eye Irritation:	0.985	Respiratory Toxicity:	0.985
Drug-induced Neurotoxicity:	0.005	Ototoxicity:	0.42
Hematotoxicity:	0.48	Drug-induced Nephrotoxicity:	0.963
Genotoxicity:	0.004	RPMI-8226 Immunitoxicity:	0.02
A549 Cytotoxicity:	0.014	Hek293 Cytotoxicity:	0.539
BCF:	2.239 ? 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:	4.939 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.475 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.127 ? 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
NPO20281	Withania aristata	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22705001]
NPO20281	Withania aristata	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20281	Withania aristata	Species	Solanaceae	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	18
Ratio IC50	1

Activity Type	# Activity
Cell line	19

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
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	900.0	nM	PMID[26176165]
NPT81	Cell line	A549	Homo sapiens	IC50	=	1500.0	nM	PMID[22928967]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	1000.0	nM	PubChem BioAssay data set
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	700.0	nM	PMID[19805565]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	700.0	nM	DrugMatrix in vitro pharmacology data
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	900.0	nM	PubChem BioAssay data set
NPT189	Cell line	Vero	Chlorocebus aethiops	Ratio IC50	=	1.0	n.a.	PMID[18077363]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	3100.0	nM	PMID[28923386]
NPT81	Cell line	A549	Homo sapiens	IC50	=	4000.0	nM	PMID[28923386]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	1200.0	nM	PMID[28923386]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	800.0	nM	PMID[28923386]
NPT179	Cell line	A2780	Homo sapiens	IC50	=	47.5	nM	PMID[31008605]
NPT21798	Cell line	ARPE-19	Homo sapiens	IC50	=	12.4	nM	PMID[31008605]

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 NPC470494 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	19008
0.1-0.2	26736
0.2-0.3	3937
0.3-0.4	97
0.4-0.5	34
0.5-0.6	33
0.6-0.7	6
0.7-0.8	1
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8592	High Similarity	NPC20302
0.8	Intermediate Similarity	NPC286528
0.7922	Intermediate Similarity	NPC3381
0.7778	Intermediate Similarity	NPC140055
0.7778	Intermediate Similarity	NPC167606
0.7349	Intermediate Similarity	NPC231240
0.7333	Intermediate Similarity	NPC470495
0.6711	Remote Similarity	NPC50774
0.6667	Remote Similarity	NPC474370
0.6623	Remote Similarity	NPC709
0.6559	Remote Similarity	NPC316915
0.6296	Remote Similarity	NPC251226
0.6049	Remote Similarity	NPC183580
0.5926	Remote Similarity	NPC609580
0.5904	Remote Similarity	NPC312824
0.5904	Remote Similarity	NPC264954
0.5854	Remote Similarity	NPC88326
0.5802	Remote Similarity	NPC122056
0.5802	Remote Similarity	NPC470265
0.575	Remote Similarity	NPC243065
0.5663	Remote Similarity	NPC470493
0.561	Remote Similarity	NPC284915
0.561	Remote Similarity	NPC268530
0.5542	Remote Similarity	NPC154491
0.5542	Remote Similarity	NPC473274
0.5476	Remote Similarity	NPC470878
0.5422	Remote Similarity	NPC270929
0.5422	Remote Similarity	NPC30923
0.5422	Remote Similarity	NPC610236
0.5412	Remote Similarity	NPC153700
0.5349	Remote Similarity	NPC8369
0.5349	Remote Similarity	NPC67569
0.5349	Remote Similarity	NPC600975
0.5349	Remote Similarity	NPC602010
0.5341	Remote Similarity	NPC23786
0.5341	Remote Similarity	NPC473593
0.5294	Remote Similarity	NPC159456
0.5233	Remote Similarity	NPC473253
0.5172	Remote Similarity	NPC470492
0.5172	Remote Similarity	NPC608655
0.5116	Remote Similarity	NPC61520
0.5114	Remote Similarity	NPC609769
0.5114	Remote Similarity	NPC610140
0.5111	Remote Similarity	NPC120994
0.5057	Remote Similarity	NPC473256
0.5056	Remote Similarity	NPC606886

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470494 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6428
0.1-0.2	2569
0.2-0.3	151
0.3-0.4	1
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	1
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
0.7778	Intermediate Similarity	NPD7115	Discovery

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