NPASS Compound

Natural Product: NPC12297

Natural Product ID	NPC12297
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Clerodin
IUPAC Name	[(4R,4aR,5S,7R,8S,8aR)-8-[(3aS,5S,6aS)-3a,4,5,6a-tetrahydrofuro[2,3-b]furan-5-yl]-5-acetyloxy-7,8-dimethylspiro[2,3,5,6,7,8a-hexahydro-1H-naphthalene-4,2'-oxirane]-4a-yl]methyl acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2269422
PubChem CID	442014
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001816] Furofurans

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 65 69 0 0 0 0 0 0 0 0999 V2000 0.2825 -2.1433 1.8988 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0113 -0.9244 1.4810 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3775 0.3828 1.9098 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9457 0.5958 1.2714 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9000 0.3725 -0.2129 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0044 -0.5805 -0.6441 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2356 0.0601 -0.2503 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4557 -0.5255 -0.4869 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4478 -1.6606 -1.0704 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7612 0.0732 -0.1107 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4421 0.0782 -0.7663 C 0 0 2 0 0 0 0 0 0 0 0 0 0.2308 -0.3132 -2.2165 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5516 0.6445 -3.0141 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5256 1.5288 -2.3387 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3287 1.6997 -0.8694 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7726 2.9811 -0.3401 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0982 2.5843 -0.1832 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3252 -0.8510 -0.0133 C 0 0 2 0 0 0 0 0 0 0 0 0 1.3306 -2.2554 -0.5380 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7426 -0.3293 -0.0645 C 0 0 2 0 0 0 0 0 0 0 0 0 3.3541 -0.1705 -1.3974 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8370 0.0137 -1.0048 C 0 0 1 0 0 0 0 0 0 0 0 0 5.1495 1.4231 -0.7609 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4782 1.5886 0.5291 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4088 0.3722 1.1840 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8794 -0.6228 0.3561 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6368 -1.0680 0.6998 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8985 -0.2444 1.9066 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9453 0.2198 2.6571 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0803 1.4529 2.7983 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8656 -0.7843 3.2634 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0098 -2.8960 2.2927 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4251 -1.8487 2.7296 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3108 -2.6622 1.1529 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9776 -0.9305 2.0882 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1187 1.1815 1.6105 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3212 0.4485 3.0105 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2666 1.6479 1.5360 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9693 -1.5386 -0.1062 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0329 -0.7980 -1.7063 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1040 -0.2773 0.8823 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4868 -0.2002 -0.9107 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7040 1.1801 -0.0589 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9804 1.0787 -0.8396 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2191 -0.4447 -2.7543 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2032 -1.3487 -2.2670 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1395 0.0406 -3.7736 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1281 1.2575 -3.6808 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4978 2.5360 -2.8049 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5923 1.1825 -2.4824 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0884 2.9752 0.5308 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5540 3.8159 -1.0399 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9352 -2.4037 -1.4458 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6937 -2.9180 0.2983 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3161 -2.6442 -0.7827 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7305 0.6909 0.4210 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1056 0.7585 -1.9345 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3709 -1.0839 -2.0221 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5159 -0.5119 -1.6723 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1308 2.2384 -1.4814 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7510 2.5328 0.9671 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5950 -1.4844 0.3678 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2582 -1.6590 3.6058 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4103 -0.3623 4.1309 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5262 -1.1505 2.4660 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 1 6 7 1 0 7 8 1 0 8 9 2 0 8 10 1 0 5 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 11 18 1 0 18 19 1 6 18 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 1 0 26 27 1 0 4 28 1 0 28 29 1 0 29 30 2 0 29 31 1 0 18 2 1 0 27 20 1 0 15 5 1 0 26 22 1 0 15 17 1 1 1 32 1 0 1 33 1 0 1 34 1 0 2 35 1 1 3 36 1 0 3 37 1 0 4 38 1 6 6 39 1 0 6 40 1 0 10 41 1 0 10 42 1 0 10 43 1 0 11 44 1 6 12 45 1 0 12 46 1 0 13 47 1 0 13 48 1 0 14 49 1 0 14 50 1 0 16 51 1 0 16 52 1 0 19 53 1 0 19 54 1 0 19 55 1 0 20 56 1 1 21 57 1 0 21 58 1 0 22 59 1 6 23 60 1 0 24 61 1 0 26 62 1 6 31 63 1 0 31 64 1 0 31 65 1 0 M END

Standard InCHIKey	CNIWQELMLPUFOS-NVSXQWMQSA-N
Standard InCHI	InChI=1S/C24H34O7/c1-14-10-20(30-16(3)26)24(13-28-15(2)25)18(6-5-8-23(24)12-29-23)22(14,4)19-11-17-7-9-27-21(17)31-19/h7,9,14,17-21H,5-6,8,10-13H2,1-4H3/t14-,17-,18-,19+,20+,21+,22+,23+,24+/m1/s1
SMILES	C[C@@H]1C[C@@H]([C@]2(COC(=O)C)[C@H](CCC[C@@]32CO3)[C@@]1(C)[C@@H]1C[C@H]2C=CO[C@H]2O1)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	434.23	Volume:	434.5 ? Van der Waals volume.
Dense:	0.999	LogP:	2.083 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.318 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.171 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	25.0
TPSA:	83.59 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.496	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.72	Fsp³:	0.833
MCE-18:	117.818 ? 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:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.585	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.011 ? 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:	0.271	Promiscuous compounds:	0.859

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.839	MDCK Permeability:	-4.682
Pgp-inhibitor:	0.762	Pgp-substrate:	0.129
PAMPA:	0.442 ? 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%):	0.115	30% Bioavailability (F30%):	0.169
50% Bioavailability (F50%):	0.593

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.028	MRP1:	0.858
Plasma Protein Binding (PPB):	36.836%	Volume Distribution (VD):	-0.206
Fu:	60.271% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.938	BCRP inhibitor:	0.478
BSEP inhibitor:	0.978

ADMET: Metabolism

CYP1A2-inhibitor:	0.582	CYP1A2-substrate:	0.008
CYP2C19-inhibitor:	0.323	CYP2C19-substrate:	0.006
CYP2C9-inhibitor:	0.045	CYP2C9-substrate:	0.678
CYP2D6-inhibitor:	0.006	CYP2D6-substrate:	0.028
CYP3A4-inhibitor:	0.017	CYP3A4-substrate:	0.135
CYP2B6-substrate:	0.167	CYP2C8-inhibitor:	0.754
HLM stability:	0.588 ? 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):

6.286

Half-life (T1/2):

1.025

ADMET: Toxicity

hERG Blockers:	0.082	hERG Blockers (10um):	0.567
Human Hepatotoxicity (H-HT):	0.593	Drug-induced Liver Injury (DILI):	0.387
AMES Toxicity:	0.774	Rat Oral Acute Toxicity:	0.795
Maximum Recommended Daily Dose:	0.905	Skin Sensitization:	0.985
Carcinogencity:	0.541	Eye Corrosion:	0.026
Eye Irritation:	0.47	Respiratory Toxicity:	0.502
Drug-induced Neurotoxicity:	0.275	Ototoxicity:	0.349
Hematotoxicity:	0.306	Drug-induced Nephrotoxicity:	0.205
Genotoxicity:	0.792	RPMI-8226 Immunitoxicity:	0.175
A549 Cytotoxicity:	0.07	Hek293 Cytotoxicity:	0.316
BCF:	1.0 ? 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:	3.799 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.653 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.056 ? 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
NPO33100	clerodendron sp.	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12617583]
NPO16812	Ajuga bracteosa	Species	Lamiaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[21539300]
NPO16812	Ajuga bracteosa	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16812	Ajuga bracteosa	Species	Lamiaceae	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
AFI	2
Activity	20
TIME	8
mortality	4

Activity Type	# Activity
Organism	34

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
NPT1193	Organism	Athalia rosae ruficornis	Athalia rosae ruficornis	Activity	=	80.0	%	DOI[10.1016/S0305-1978(03)00160-1]
NPT1193	Organism	Athalia rosae ruficornis	Athalia rosae ruficornis	Activity	=	40.0	%	DOI[10.1016/S0305-1978(03)00160-1]
NPT776	Organism	Spodoptera littoralis	Spodoptera littoralis	Activity	=	100.0	%	PMID[12617583]
NPT1192	Organism	Spodoptera frugiperda	Spodoptera frugiperda	AFI	=	78.0	%	DOI[10.1016/S0040-4020(99)00612-2]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	TIME	=	192.0	hr	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	TIME	=	168.0	hr	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	TIME	=	201.6	hr	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	Activity	=	8.0	%	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	Activity	=	9.6	%	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	Activity	=	64.0	%	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	Activity	=	63.2	%	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	Activity	=	270.2	mg	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	Activity	=	250.2	mg	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	TIME	=	261.6	hr	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	TIME	=	278.4	hr	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	TIME	=	343.2	hr	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	TIME	=	355.2	hr	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	Activity	=	72.0	%	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	Activity	=	80.0	%	PMID[12617583]
NPT1191	Organism	Spodoptera exempta	Spodoptera exempta	AFI	=	76.0	%	DOI[10.1016/S0040-4020(99)00612-2]
NPT1194	Organism	Earias vitella	Earias vitella	Activity	=	4.0	%	PMID[12617583]
NPT1194	Organism	Earias vitella	Earias vitella	Activity	=	8.0	%	PMID[12617583]
NPT1194	Organism	Earias vitella	Earias vitella	Activity	=	68.6	%	PMID[12617583]
NPT1194	Organism	Earias vitella	Earias vitella	Activity	=	60.0	%	PMID[12617583]
NPT1194	Organism	Earias vitella	Earias vitella	Activity	=	60.4	mg	PMID[12617583]
NPT1194	Organism	Earias vitella	Earias vitella	Activity	=	62.87	%	PMID[12617583]
NPT1194	Organism	Earias vitella	Earias vitella	Activity	=	72.13	%	PMID[12617583]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1175	Organism	Spodoptera litura	Spodoptera litura	mortality	=	27.0	%	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	mortality	=	24.5	%	PMID[12617583]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	mortality	=	35.2	%	PMID[12617583]

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 NPC12297 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	22752
0.1-0.2	25587
0.2-0.3	1487
0.3-0.4	17
0.4-0.5	7
0.5-0.6	3
0.6-0.7	3
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	Natural Product ID
0.7344	Intermediate Similarity	NPC113976
0.7344	Intermediate Similarity	NPC198549
0.6567	Remote Similarity	NPC235402
0.6164	Remote Similarity	NPC291414
0.6	Remote Similarity	NPC305939
0.5921	Remote Similarity	NPC86217
0.5286	Remote Similarity	NPC93411
0.5217	Remote Similarity	NPC609068

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC12297 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7097
0.1-0.2	2037
0.2-0.3	16
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