NPASS Compound

Natural Product: NPC254558

Natural Product ID	NPC254558
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	UPKPCBUBBFEYEF-OVJAYBENSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL443569
PubChem CID	11763676
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0002995] Pentacarboxylic acids 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 2D 85 89 0 0 0 0 0 0 0 0999 V2000 -1.5305 -1.3311 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4980 -2.4192 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1000 -3.7949 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5903 -3.9648 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4827 -2.7591 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8943 -1.3846 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3943 -1.3846 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8943 -1.3846 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6443 -2.6836 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2309 -4.1255 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1443 -2.6836 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6443 -0.0855 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8943 1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3077 2.6554 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2760 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 -1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 -0.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5241 0.5932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3442 2.2172 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3907 1.0037 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0788 2.4709 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8068 3.2659 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1935 3.4746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7934 0.8787 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2029 0.3656 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8131 -1.0046 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3520 1.3298 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7615 0.8168 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9106 1.7810 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6501 3.2582 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2406 3.7712 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0915 2.8070 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5151 -3.8472 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9737 -3.4972 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0252 -2.4275 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0061 -4.5853 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5800 -6.0235 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6124 -7.1117 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0710 -6.7616 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4972 -5.3234 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4647 -4.2353 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1642 -5.4030 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1966 -6.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6870 -6.3215 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7705 -7.9293 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6879 -0.3769 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6186 -2.3635 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7245 -0.0660 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7489 -3.2470 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3586 -4.1449 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1914 -5.2921 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9327 -4.6342 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9472 -2.4347 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0986 -0.0602 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3943 -2.8846 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6331 -2.5007 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5073 -4.1390 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1443 -1.1836 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0626 -0.5738 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8578 2.6401 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6004 -0.7041 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0159 0.4364 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8615 2.0548 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5503 -0.9066 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6560 3.6844 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8384 2.0865 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0040 2.8749 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3083 4.4783 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1898 4.5893 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1972 2.3599 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0220 -0.6604 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 10.3201 1.2679 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7992 4.2224 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9801 5.2484 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6820 3.3201 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1750 -6.5488 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1863 -8.5499 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1035 -7.8498 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9557 -4.9734 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3780 -3.0454 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3444 -9.3675 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2087 -8.3555 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3323 -7.5032 0.0000 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 1 7 8 1 0 8 9 1 0 9 10 2 0 9 11 1 0 6 12 1 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 1 0 16 17 1 0 17 18 1 6 18 19 1 0 19 20 1 0 19 21 1 0 16 22 1 0 22 23 1 0 23 24 2 0 23 25 1 0 12 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 5 35 1 0 35 36 1 0 36 37 2 0 36 38 1 0 38 39 2 0 39 40 1 0 40 41 2 0 41 42 1 0 42 43 2 0 4 44 1 0 44 45 1 0 45 46 2 0 45 47 1 0 17 2 1 0 34 29 1 0 43 38 1 0 17 6 1 0 19 15 1 0 1 48 1 0 1 49 1 0 1 50 1 0 2 51 1 6 3 52 1 0 3 53 1 0 4 54 1 6 5 55 1 6 7 56 1 0 7 57 1 0 11 58 1 0 11 59 1 0 11 60 1 0 12 61 1 6 15 62 1 1 16 63 1 6 20 64 1 0 20 65 1 0 20 66 1 0 21 67 1 0 21 68 1 0 21 69 1 0 25 70 1 0 25 71 1 0 25 72 1 0 30 73 1 0 31 74 1 0 32 75 1 0 33 76 1 0 34 77 1 0 39 78 1 0 40 79 1 0 41 80 1 0 42 81 1 0 43 82 1 0 47 83 1 0 47 84 1 0 47 85 1 0 M END

Standard InCHIKey	UPKPCBUBBFEYEF-OVJAYBENSA-N
Standard InCHI	InChI=1S/C35H38O12/c1-19-17-25(43-21(3)37)28(45-31(40)23-13-9-7-10-14-23)34(18-42-20(2)36)30(46-32(41)24-15-11-8-12-16-24)27(39)26-29(44-22(4)38)35(19,34)47-33(26,5)6/h7-16,19,25-26,28-30H,17-18H2,1-6H3/t19-,25+,26-,28+,29-,30-,34+,35-/m1/s1
SMILES	C[C@@H]1C[C@@H]([C@@H]([C@@]2(COC(=O)C)[C@@H](C(=O)[C@@H]3[C@H]([C@]12OC3(C)C)OC(=O)C)OC(=O)c1ccccc1)OC(=O)c1ccccc1)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	650.24	Volume:	644.979 ? Van der Waals volume.
Dense:	1.008	LogP:	3.452 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.207 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.002 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	13.0	Rigid Bonds:	32.0
TPSA:	157.8 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.302	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.88	Fsp³:	0.486
MCE-18:	166.615 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.413	Fluc inhibitor:	0.011 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.006 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.382 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.206	Promiscuous compounds:	0.055

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.364	MDCK Permeability:	-4.774
Pgp-inhibitor:	0.886	Pgp-substrate:	0.014
PAMPA:	0.064 ? 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):	0.0
20% Bioavailability (F20%):	0.0	30% Bioavailability (F30%):	0.003
50% Bioavailability (F50%):	0.469

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.958	MRP1:	1.0
Plasma Protein Binding (PPB):	92.294%	Volume Distribution (VD):	-0.387
Fu:	8.916% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.983	BCRP inhibitor:	0.001
BSEP inhibitor:	0.675

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.156
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.304
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.033
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.006
CYP3A4-inhibitor:	0.883	CYP3A4-substrate:	0.789
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.994 ? 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):

1.739

Half-life (T1/2):

1.17

ADMET: Toxicity

hERG Blockers:	0.028	hERG Blockers (10um):	0.309
Human Hepatotoxicity (H-HT):	0.054	Drug-induced Liver Injury (DILI):	0.993
AMES Toxicity:	0.906	Rat Oral Acute Toxicity:	0.141
Maximum Recommended Daily Dose:	0.29	Skin Sensitization:	1.0
Carcinogencity:	0.863	Eye Corrosion:	0.0
Eye Irritation:	0.421	Respiratory Toxicity:	0.02
Drug-induced Neurotoxicity:	0.874	Ototoxicity:	0.153
Hematotoxicity:	0.173	Drug-induced Nephrotoxicity:	0.806
Genotoxicity:	0.733	RPMI-8226 Immunitoxicity:	0.22
A549 Cytotoxicity:	0.821	Hek293 Cytotoxicity:	0.816
BCF:	0.721 ? 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:	3.65 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.961 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.657 ? 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
NPO33107	zinowiewia costaricensis	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15974580]
NPO33107	zinowiewia costaricensis	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
Ki	3
Imax	1
Reversal ability	6
Activity	5
Intrinsic Toxicity	6

Activity Type	# Activity
Cell line	14
Individual protein	3
Others	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT668	Individual protein	P-glycoprotein 1	Homo sapiens	Ki	=	1630.0	nM	PMID[18829331]
NPT668	Individual protein	P-glycoprotein 1	Homo sapiens	Ki	=	1621.81	nM	PMID[20634081]
NPT668	Individual protein	P-glycoprotein 1	Homo sapiens	Imax	=	81.6	%	PMID[17850057]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT886	Cell line	NIH3T3	Mus musculus	Ki	=	1633.0	nM	PMID[25856683]
NPT886	Cell line	NIH3T3	Mus musculus	Reversal ability	=	11.75	n.a.	PMID[15974580]
NPT886	Cell line	NIH3T3	Mus musculus	Reversal ability	=	6.21	n.a.	PMID[15974580]
NPT886	Cell line	NIH3T3	Mus musculus	Reversal ability	=	4.21	n.a.	PMID[15974580]
NPT886	Cell line	NIH3T3	Mus musculus	Reversal ability	=	233.37	n.a.	PMID[15974580]
NPT886	Cell line	NIH3T3	Mus musculus	Reversal ability	=	213.64	n.a.	PMID[15974580]
NPT886	Cell line	NIH3T3	Mus musculus	Reversal ability	=	5.72	n.a.	PMID[15974580]
NPT80	Cell line	Raji	Homo sapiens	Activity	=	60.0	%	PMID[17844995]
NPT886	Cell line	NIH3T3	Mus musculus	Intrinsic Toxicity	=	6.67	n.a.	PMID[15974580]
NPT886	Cell line	NIH3T3	Mus musculus	Intrinsic Toxicity	=	29.4	n.a.	PMID[15974580]
NPT886	Cell line	NIH3T3	Mus musculus	Intrinsic Toxicity	=	11.03	n.a.	PMID[15974580]
NPT886	Cell line	NIH3T3	Mus musculus	Intrinsic Toxicity	=	0.0	n.a.	PMID[15974580]
NPT886	Cell line	NIH3T3	Mus musculus	Intrinsic Toxicity	=	37.76	n.a.	PMID[15974580]
NPT886	Cell line	NIH3T3	Mus musculus	Intrinsic Toxicity	=	18.07	n.a.	PMID[15974580]
NPT2	Others	Unspecified	n.a.	Activity	=	13.3	%	PMID[19813743]
NPT2	Others	Unspecified	n.a.	Activity	=	53.3	%	PMID[18723353]
NPT2	Others	Unspecified	n.a.	Activity	=	86.7	%	PMID[19445517]
NPT2	Others	Unspecified	n.a.	Activity	=	100.0	%	PMID[16562829]

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 NPC254558 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	18657
0.1-0.2	29323
0.2-0.3	1336
0.3-0.4	404
0.4-0.5	85
0.5-0.6	33
0.6-0.7	13
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	3
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9355	High Similarity	NPC471107
0.9355	High Similarity	NPC471100
0.9355	High Similarity	NPC605884
0.7246	Intermediate Similarity	NPC483842
0.7206	Intermediate Similarity	NPC473060
0.7	Intermediate Similarity	NPC148062
0.6986	Remote Similarity	NPC282239
0.6857	Remote Similarity	NPC147880
0.6757	Remote Similarity	NPC471102
0.6714	Remote Similarity	NPC51314
0.662	Remote Similarity	NPC479047
0.662	Remote Similarity	NPC291638
0.6575	Remote Similarity	NPC471103
0.6562	Remote Similarity	NPC216137
0.6528	Remote Similarity	NPC137718
0.6351	Remote Similarity	NPC479044
0.6267	Remote Similarity	NPC479043
0.6164	Remote Similarity	NPC4341
0.6081	Remote Similarity	NPC147217
0.5946	Remote Similarity	NPC191082
0.5897	Remote Similarity	NPC51602
0.5867	Remote Similarity	NPC43241
0.5802	Remote Similarity	NPC479040
0.5769	Remote Similarity	NPC106895
0.5658	Remote Similarity	NPC177340
0.5616	Remote Similarity	NPC481047
0.5616	Remote Similarity	NPC481045
0.56	Remote Similarity	NPC472577
0.557	Remote Similarity	NPC184747
0.5526	Remote Similarity	NPC90257
0.5526	Remote Similarity	NPC483845
0.5526	Remote Similarity	NPC69357
0.5479	Remote Similarity	NPC195647
0.5455	Remote Similarity	NPC139067
0.5395	Remote Similarity	NPC17877
0.5395	Remote Similarity	NPC483902
0.5316	Remote Similarity	NPC483844
0.527	Remote Similarity	NPC200592
0.527	Remote Similarity	NPC610542
0.5256	Remote Similarity	NPC67777
0.5125	Remote Similarity	NPC41481
0.5125	Remote Similarity	NPC306146
0.5125	Remote Similarity	NPC483841
0.5122	Remote Similarity	NPC483848
0.5067	Remote Similarity	NPC473081
0.5062	Remote Similarity	NPC252314
0.5062	Remote Similarity	NPC11685
0.5062	Remote Similarity	NPC16912
0.5062	Remote Similarity	NPC609924
0.506	Remote Similarity	NPC483849
0.5057	Remote Similarity	NPC75600
0.5057	Remote Similarity	NPC483884

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC254558 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4185
0.1-0.2	4807
0.2-0.3	158
0.3-0.4	0
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
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
		NPD

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