NPASS Compound

Natural Product: NPC84562

Natural Product ID	NPC84562
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(3Ar,5As,9As,9Br)-3A,6,6,9A-Tetramethyl-1,4,5,5A,7,8,9,9B-Octahydrobenzo[E][1]Benzofuran-2-One
IUPAC Name	(3aR,5aS,9aS,9bR)-3a,6,6,9a-tetramethyl-1,4,5,5a,7,8,9,9b-octahydrobenzo[e][1]benzofuran-2-one
Synonyms	(3aR)-(+)-Sclareolide
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL304461
PubChem CID	929262
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001634] Naphthofurans

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 44 46 0 0 0 0 0 0 0 0999 V2000 5.0188 -1.1669 -0.2741 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8588 -0.8069 0.0315 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6118 -1.3690 -0.6133 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5752 -0.7045 0.2172 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2265 0.6224 0.5138 C 0 0 1 0 0 0 0 0 0 0 0 0 3.4964 0.1435 0.9864 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5212 1.4552 -0.6854 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4342 1.3372 1.5286 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0268 1.5258 0.9649 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6010 0.2110 0.6455 C 0 0 2 0 0 0 0 0 0 0 0 0 0.2066 -0.6447 -0.2953 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0531 -0.3187 -1.7295 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4242 -2.0403 -0.1232 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8565 -2.0442 -0.5318 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7071 -0.9699 0.0117 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0401 0.3445 0.2889 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3138 1.3711 -0.7857 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7195 0.8883 1.5638 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5754 -1.1533 -1.6859 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5841 -2.4718 -0.4600 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5546 -1.2511 1.2077 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4607 2.0405 -0.4451 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7976 0.8715 -1.5922 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7638 2.2439 -0.8937 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8458 2.3820 1.6320 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4274 0.9115 2.5296 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0240 2.2617 0.1696 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5631 1.9672 1.8146 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5912 -0.3595 1.6273 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9931 -0.3818 -2.0508 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4655 0.6161 -2.0794 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5859 -1.1337 -2.3039 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1230 -2.7735 -0.7399 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3612 -2.3494 0.9484 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2723 -3.0381 -0.1803 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9667 -2.1240 -1.6552 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5117 -0.7520 -0.7543 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3012 -1.3532 0.8947 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4130 1.8241 -1.2095 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9545 0.9155 -1.5903 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9369 2.2367 -0.4179 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2210 0.4588 2.4558 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6945 1.9913 1.5307 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7945 0.5865 1.5342 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 1 0 5 7 1 6 5 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 16 18 1 0 6 2 1 0 16 10 1 0 11 4 1 0 3 19 1 0 3 20 1 0 4 21 1 1 7 22 1 0 7 23 1 0 7 24 1 0 8 25 1 0 8 26 1 0 9 27 1 0 9 28 1 0 10 29 1 1 12 30 1 0 12 31 1 0 12 32 1 0 13 33 1 0 13 34 1 0 14 35 1 0 14 36 1 0 15 37 1 0 15 38 1 0 17 39 1 0 17 40 1 0 17 41 1 0 18 42 1 0 18 43 1 0 18 44 1 0 M END

Standard InCHIKey	IMKJGXCIJJXALX-SHUKQUCYSA-N
Standard InCHI	InChI=1S/C16H26O2/c1-14(2)7-5-8-15(3)11(14)6-9-16(4)12(15)10-13(17)18-16/h11-12H,5-10H2,1-4H3/t11-,12+,15-,16+/m0/s1
SMILES	O=C1C[C@H]2[C@@](O1)(C)CC[C@@H]1[C@]2(C)CCCC1(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	250.19	Volume:	274.567 ? Van der Waals volume.
Dense:	0.911	LogP:	3.002 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.079 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.663 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	16.0
TPSA:	26.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.609	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.941	Fsp³:	0.938
MCE-18:	56.903 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.242	Fluc inhibitor:	0.142 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? 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:	0.958	Promiscuous compounds:	0.368

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.814	MDCK Permeability:	-4.762
Pgp-inhibitor:	0.753	Pgp-substrate:	0.005
PAMPA:	0.066 ? 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):	0.006
20% Bioavailability (F20%):	0.075	30% Bioavailability (F30%):	0.155
50% Bioavailability (F50%):	0.76

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.281	MRP1:	0.301
Plasma Protein Binding (PPB):	97.123%	Volume Distribution (VD):	0.355
Fu:	3.634% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.78
BSEP inhibitor:	0.916

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.692
CYP2C19-inhibitor:	0.376	CYP2C19-substrate:	0.166
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.726
CYP2D6-inhibitor:	0.023	CYP2D6-substrate:	0.108
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.992
HLM stability:	0.845 ? 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):

11.269

Half-life (T1/2):

0.739

ADMET: Toxicity

hERG Blockers:	0.065	hERG Blockers (10um):	0.34
Human Hepatotoxicity (H-HT):	0.578	Drug-induced Liver Injury (DILI):	0.309
AMES Toxicity:	0.349	Rat Oral Acute Toxicity:	0.218
Maximum Recommended Daily Dose:	0.657	Skin Sensitization:	0.993
Carcinogencity:	0.891	Eye Corrosion:	0.895
Eye Irritation:	0.987	Respiratory Toxicity:	0.401
Drug-induced Neurotoxicity:	0.523	Ototoxicity:	0.201
Hematotoxicity:	0.249	Drug-induced Nephrotoxicity:	0.898
Genotoxicity:	0.392	RPMI-8226 Immunitoxicity:	0.042
A549 Cytotoxicity:	0.083	Hek293 Cytotoxicity:	0.29
BCF:	2.279 ? 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:	4.298 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.586 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.281 ? 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
NPO5484	Arnica angustifolia	Species	Asteraceae	Eukaryota	n.a.	flower	n.a.	PMID[16644542]
NPO5484	Arnica angustifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23501116]
NPO29383	Abies holophylla	Species	Pinaceae	Eukaryota	trunk	n.a.	n.a.	PMID[24224862]
NPO29383	Abies holophylla	Species	Pinaceae	Eukaryota	Trunk	n.a.	n.a.	PMID[26812172]
NPO29383	Abies holophylla	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30063340]
NPO8104	Trocholejeunea sandvicensis	Species	Lejeuneaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1006	Ipomoea asarifolia	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29383	Abies holophylla	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8104	Trocholejeunea sandvicensis	Species	Lejeuneaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8104	Trocholejeunea sandvicensis	Species	Lejeuneaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5919	Phoebe cinnamomifolia	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8271	Aplophyllum tuberculatum	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO5919	Phoebe cinnamomifolia	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1006	Ipomoea asarifolia	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29383	Abies holophylla	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3832	Abuta pahni	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7218	Salvia montbretii	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5484	Arnica angustifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8104	Trocholejeunea sandvicensis	Species	Lejeuneaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7061	Tabernaemontana laeta	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5320	Fleischmannia multinervis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2305	Naregamia alata	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6083	Richardsonia scabra	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO7558	Primula sieboldi	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5148	Geranium saxatile	Species	Geraniaceae	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
Potency	18
Inhibition	9
IC50	2
Activity	13

Activity Type	# Activity
Individual protein	9
Cell line	15
Organism	4
Single protein	1
Others	13

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT153	Individual protein	Androgen Receptor	Homo sapiens	Potency	n.a.	54947.7	nM	PubChem BioAssay data set
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	Potency	n.a.	38570.8	nM	PubChem BioAssay data set
NPT163	Individual protein	Nuclear factor NF-kappa-B p105 subunit	Homo sapiens	Potency	n.a.	61652.4	nM	PubChem BioAssay data set
NPT67	Individual protein	Cholinesterase	Equus caballus	Inhibition	=	-1.03	%	PMID[23062825]
NPT20556	Single protein	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-4.371	%	DOI[10.6019/CHEMBL4495564]
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	6.93	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	8.2	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT8	Individual protein	DNA polymerase iota	Homo sapiens	Potency	n.a.	89125.1	nM	PubChem BioAssay data set
NPT66	Individual protein	Acetylcholinesterase	Electrophorus electricus	Inhibition	=	-6.49	%	PMID[23062825]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT737	Cell line	HUVEC	Homo sapiens	IC50	>	50.0	ug.mL-1	PMID[12781184]
NPT34	Cell line	BV-2	Mus musculus	IC50	=	20300.0	nM	PMID[30063340]
NPT34	Cell line	BV-2	Mus musculus	Activity	=	131.3	%	PMID[30063340]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	96.6	%	PMID[31022551]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	99.3	%	PMID[31022551]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	97.2	%	PMID[31022551]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	95.9	%	PMID[31022551]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	104.8	%	PMID[31022551]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	101.0	%	PMID[31022551]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	79.9	%	PMID[31022551]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	63.9	%	PMID[31022551]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	94.6	%	PMID[31022551]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	100.3	%	PMID[31022551]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	93.8	%	PMID[31022551]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	89.7	%	PMID[31022551]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	9285.0	nM	PubChem BioAssay data set
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	0.14	%	DOI[10.21203/rs.3.rs-23951/v1]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	0.22	%	DOI[10.6019/CHEMBL4495565]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	54482.7	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	48972.2	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	15486.4	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	61130.6	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	68589.6	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	30899.4	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	48557.7	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	2818.4	nM	PubChem BioAssay data set

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 NPC84562 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	18499
0.1-0.2	27258
0.2-0.3	3669
0.3-0.4	384
0.4-0.5	40
0.5-0.6	5
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	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC608369
0.6316	Remote Similarity	NPC478126
0.5682	Remote Similarity	NPC607221
0.5556	Remote Similarity	NPC42630
0.5417	Remote Similarity	NPC479669
0.5102	Remote Similarity	NPC137587
0.5088	Remote Similarity	NPC166857

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC84562 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6864
0.1-0.2	2154
0.2-0.3	131
0.3-0.4	1
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