NPASS Compound

Natural Product: NPC145442

Natural Product ID	NPC145442
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	AIFNAMVERSBWPS-ZCFIWIBFSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	83412
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000123] Benzopyrans [CHEMONTID:0003411] 2-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 27 28 0 0 0 0 0 0 0 0999 V2000 -3.7280 0.6718 -0.9971 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5053 0.6342 -0.0884 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2410 0.5300 -0.8735 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0903 0.0347 -0.0979 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2238 0.2683 -0.5096 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3114 -0.1863 0.1992 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1318 -0.9017 1.3624 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8392 -1.1361 1.7748 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2740 -0.6764 1.0585 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6238 -0.9356 1.5171 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7825 -1.5994 2.5959 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6976 -0.4641 0.7847 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5617 -1.8443 2.9289 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6061 0.0828 -0.2695 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8258 0.8125 -1.4570 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6055 1.4407 -1.7782 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6026 0.9788 -0.3638 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9683 -0.3332 -1.4039 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5206 1.5787 0.4941 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9508 1.5137 -1.2952 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3639 -0.1556 -1.7550 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3715 0.8264 -1.4172 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9766 -1.2724 1.9413 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5338 -2.8642 2.8527 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9154 0.8923 -1.5959 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3445 1.8100 -1.3021 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3123 0.2945 -2.3052 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 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 10 12 1 0 8 13 1 0 6 14 1 0 14 15 1 0 12 2 1 0 9 4 1 0 1 16 1 0 1 17 1 0 1 18 1 0 2 19 1 1 3 20 1 0 3 21 1 0 5 22 1 0 7 23 1 0 13 24 1 0 15 25 1 0 15 26 1 0 15 27 1 0 M END

Standard InCHIKey	AIFNAMVERSBWPS-ZCFIWIBFSA-N
Standard InCHI	InChI=1S/C11H12O4/c1-6-3-7-4-8(14-2)5-9(12)10(7)11(13)15-6/h4-6,12H,3H2,1-2H3/t6-/m1/s1
SMILES	C[C@@H]1Cc2cc(cc(c2C(=O)O1)O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	208.07	Volume:	206.314 ? Van der Waals volume.
Dense:	1.009	LogP:	2.34 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.54 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.224 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	12.0
TPSA:	55.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.71	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.772	Fsp³:	0.364
MCE-18:	39.2 ? 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:	0.201	Fluc inhibitor:	0.217 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.283 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.24 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.662	Promiscuous compounds:	0.473

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.728	MDCK Permeability:	-4.671
Pgp-inhibitor:	0.856	Pgp-substrate:	0.018
PAMPA:	0.047 ? 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):	0.033
20% Bioavailability (F20%):	0.071	30% Bioavailability (F30%):	0.65
50% Bioavailability (F50%):	0.884

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.168	MRP1:	0.788
Plasma Protein Binding (PPB):	84.099%	Volume Distribution (VD):	0.04
Fu:	15.351% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.797
BSEP inhibitor:	0.991

ADMET: Metabolism

CYP1A2-inhibitor:	0.813	CYP1A2-substrate:	0.646
CYP2C19-inhibitor:	0.024	CYP2C19-substrate:	0.034
CYP2C9-inhibitor:	0.835	CYP2C9-substrate:	0.919
CYP2D6-inhibitor:	0.088	CYP2D6-substrate:	0.681
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.335
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.264
HLM stability:	0.847 ? 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):

5.603

Half-life (T1/2):

1.12

ADMET: Toxicity

hERG Blockers:	0.067	hERG Blockers (10um):	0.341
Human Hepatotoxicity (H-HT):	0.472	Drug-induced Liver Injury (DILI):	0.783
AMES Toxicity:	0.825	Rat Oral Acute Toxicity:	0.317
Maximum Recommended Daily Dose:	0.488	Skin Sensitization:	0.93
Carcinogencity:	0.671	Eye Corrosion:	0.462
Eye Irritation:	0.983	Respiratory Toxicity:	0.529
Drug-induced Neurotoxicity:	0.563	Ototoxicity:	0.293
Hematotoxicity:	0.243	Drug-induced Nephrotoxicity:	0.797
Genotoxicity:	0.596	RPMI-8226 Immunitoxicity:	0.125
A549 Cytotoxicity:	0.318	Hek293 Cytotoxicity:	0.224
BCF:	1.155 ? 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:	3.697 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.072 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.169 ? 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
NPO64914	Astragalus membranaceus + Aspergillus sp. symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[ 33716326]
NPO64672	Ectyoplasia ferox + Coniothyrium sp. symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[ 9917295]
NPO64914	Astragalus membranaceus + Aspergillus sp. symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	DOI[10.1007/s10600-020-03100-4]
NPO33476	microsphaeropsis sp.	Species	n.a.	Eukaryota	n.a.	n.a.	n.a.	PMID[10869191]
NPO33476	microsphaeropsis sp.	Species	n.a.	Eukaryota	n.a.	n.a.	n.a.	PMID[12027766]
NPO33476	microsphaeropsis sp.	Species	n.a.	Eukaryota	n.a.	n.a.	n.a.	PMID[32243151]
NPO40084	Coniothyrium sp.	Species	Coniothyriaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9917295]
NPO33476	microsphaeropsis sp.	Species	n.a.	Eukaryota	n.a.	n.a.	n.a.	PMID[9917295]
NPO40084	Coniothyrium sp.	Species	Coniothyriaceae	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
MIC	2
EC90	1
EC50	1

Activity Type	# Activity
Organism	4

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
NPT1198	Organism	Magnaporthe grisea	Magnaporthe grisea	MIC	=	200.0	ug.mL-1	PMID[14738379]
NPT1198	Organism	Magnaporthe grisea	Magnaporthe grisea	EC90	=	106.0	ug ml-1	PMID[14738379]
NPT1198	Organism	Magnaporthe grisea	Magnaporthe grisea	EC50	=	47.0	ug.mL-1	PMID[14738379]
NPT1780	Organism	Davidiella tassiana	Davidiella tassiana	MIC	=	25.0	ug	PMID[14738379]

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 NPC145442 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	19019
0.1-0.2	24676
0.2-0.3	5672
0.3-0.4	405
0.4-0.5	73
0.5-0.6	11
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
0.68	Remote Similarity	NPC469542
0.6296	Remote Similarity	NPC212484
0.5909	Remote Similarity	NPC235115
0.5614	Remote Similarity	NPC610162
0.5556	Remote Similarity	NPC214702
0.5556	Remote Similarity	NPC470831
0.5556	Remote Similarity	NPC599777
0.5417	Remote Similarity	NPC610217
0.5349	Remote Similarity	NPC180905
0.5217	Remote Similarity	NPC135837
0.5208	Remote Similarity	NPC487520
0.5106	Remote Similarity	NPC90411
0.5079	Remote Similarity	NPC602776

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC145442 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3328
0.1-0.2	5499
0.2-0.3	317
0.3-0.4	6
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