NPASS Compound

Natural Product: NPC30006

Natural Product ID	NPC30006
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	JGIIGTJEQMRDLG-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	86091752
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000123] Benzopyrans [CHEMONTID:0003410] 1-benzopyrans [CHEMONTID:0003522] 2,2-dimethyl-1-benzopyrans

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 30 31 0 0 0 0 0 0 0 0999 V2000 -3.5835 0.0242 -1.6134 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8109 -0.0017 -0.2939 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7708 -0.4602 0.8284 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3853 1.3736 -0.0349 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1469 1.7078 0.1640 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0978 0.7014 0.1374 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2260 1.0745 0.3525 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1957 0.1002 0.3213 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8279 -1.2073 0.0795 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5252 -1.5753 -0.1322 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4527 -0.6024 -0.1023 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7983 -0.9623 -0.3179 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5958 0.4862 0.5475 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9108 1.6863 0.7670 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6079 -0.6012 0.5040 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8850 -0.1446 0.7263 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2662 -0.8227 -1.7125 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8806 0.0984 -2.4430 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2071 0.9570 -1.5877 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2256 -1.4163 0.4710 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4981 0.3139 1.0674 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1078 -0.7460 1.6736 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1658 2.1422 -0.0122 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8221 2.7324 0.3578 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4525 2.1232 0.5382 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5975 -1.9891 0.0534 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2383 -2.6145 -0.3238 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2971 -1.3362 1.3021 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5915 -1.1433 -0.4778 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2680 0.1018 -0.1716 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 8 13 1 0 13 14 2 0 13 15 1 0 15 16 1 0 12 2 1 0 11 6 1 0 1 17 1 0 1 18 1 0 1 19 1 0 3 20 1 0 3 21 1 0 3 22 1 0 4 23 1 0 5 24 1 0 7 25 1 0 9 26 1 0 10 27 1 0 15 28 1 0 15 29 1 0 16 30 1 0 M END

Standard InCHIKey	JGIIGTJEQMRDLG-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C13H14O3/c1-13(2)6-5-10-7-9(11(15)8-14)3-4-12(10)16-13/h3-7,14H,8H2,1-2H3
SMILES	CC1(C)C=Cc2cc(ccc2O1)C(=O)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	218.09	Volume:	229.48 ? Van der Waals volume.
Dense:	0.95	LogP:	2.42 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.449 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.625 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	12.0
TPSA:	46.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.773	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.644	Fsp³:	0.308
MCE-18:	27.529 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.076	Fluc inhibitor:	0.336 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.218 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.136 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.718	Promiscuous compounds:	0.351

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.661	MDCK Permeability:	-4.611
Pgp-inhibitor:	0.279	Pgp-substrate:	0.147
PAMPA:	0.368 ? 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):	0.031
20% Bioavailability (F20%):	0.246	30% Bioavailability (F30%):	0.446
50% Bioavailability (F50%):	0.855

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.646	MRP1:	0.476
Plasma Protein Binding (PPB):	81.787%	Volume Distribution (VD):	0.109
Fu:	20.736% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.816
OATP1B3 inhibitor:	0.923	BCRP inhibitor:	0.627
BSEP inhibitor:	0.876

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.149
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.277
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.011
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.068
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.765
HLM stability:	0.695 ? 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):

7.298

Half-life (T1/2):

1.025

ADMET: Toxicity

hERG Blockers:	0.111	hERG Blockers (10um):	0.392
Human Hepatotoxicity (H-HT):	0.331	Drug-induced Liver Injury (DILI):	0.164
AMES Toxicity:	0.719	Rat Oral Acute Toxicity:	0.486
Maximum Recommended Daily Dose:	0.324	Skin Sensitization:	0.315
Carcinogencity:	0.695	Eye Corrosion:	0.172
Eye Irritation:	0.952	Respiratory Toxicity:	0.931
Drug-induced Neurotoxicity:	0.485	Ototoxicity:	0.346
Hematotoxicity:	0.373	Drug-induced Nephrotoxicity:	0.155
Genotoxicity:	0.203	RPMI-8226 Immunitoxicity:	0.054
A549 Cytotoxicity:	0.055	Hek293 Cytotoxicity:	0.205
BCF:	0.949 ? 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:	3.613 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.074 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.414 ? 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
NPO19134	Boronia bipinnata	Species	Rutaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[18662038]
NPO28004	Pseudodistoma megalarva	Species	Pseudodistomidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9358640]
NPO18310	Pecten jacobaeus	Species	Pectinidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16661	Duboisia myoporoides	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26523	Alicyclobacillus acidocaldarius	Species	Alicyclobacillaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19134	Boronia bipinnata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8147	Calea hispida	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22725	Cirsium microspicatum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17194	Linum capitatum	Species	Linaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10631	Gerbera lanuginosa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13648	Phialocephala fortinii	Species	n.a.	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28004	Pseudodistoma megalarva	Species	Pseudodistomidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18581	Pyrrosia davidii	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17285	Taraxacum udum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15676	Tricholoma scalpturatum	Species	Tricholomataceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15368	Trifolium medium	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13558	Mundulea suberosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18581	Pyrrosia davidii	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18581	Pyrrosia davidii	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19134	Boronia bipinnata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13648	Phialocephala fortinii	Species	n.a.	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18581	Pyrrosia davidii	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15676	Tricholoma scalpturatum	Species	Tricholomataceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18310	Pecten jacobaeus	Species	Pectinidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22725	Cirsium microspicatum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26523	Alicyclobacillus acidocaldarius	Species	Alicyclobacillaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO17285	Taraxacum udum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8147	Calea hispida	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28004	Pseudodistoma megalarva	Species	Pseudodistomidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16661	Duboisia myoporoides	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15368	Trifolium medium	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13558	Mundulea suberosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10631	Gerbera lanuginosa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17194	Linum capitatum	Species	Linaceae	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

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

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 NPC30006 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	16443
0.1-0.2	31146
0.2-0.3	2036
0.3-0.4	196
0.4-0.5	29
0.5-0.6	6
0.6-0.7	2
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
0.775	Intermediate Similarity	NPC259631
0.6591	Remote Similarity	NPC161696
0.6136	Remote Similarity	NPC608132
0.5745	Remote Similarity	NPC90903
0.5625	Remote Similarity	NPC165556
0.56	Remote Similarity	NPC162476
0.5417	Remote Similarity	NPC151113
0.5319	Remote Similarity	NPC229646
0.5208	Remote Similarity	NPC609025

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC30006 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2818
0.1-0.2	6163
0.2-0.3	168
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