NPASS Compound

Natural Product: NPC580405

Natural Product ID	NPC580405
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	96238-95-8
IUPAC Name	3,5,7,8-tetrahydroxy-2-(4-methoxyphenyl)chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 35 37 0 0 0 0 0 0 0 0999 V2000 6.3502 0.2094 0.6140 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3012 -0.3084 1.3988 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0057 -0.1686 0.9512 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9737 -0.6672 1.7035 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6751 -0.5358 1.2708 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3522 0.0981 0.0702 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0470 0.1911 -0.3078 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4954 0.7864 -1.4572 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3564 1.3633 -2.3789 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8804 0.7971 -1.6835 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2992 1.3400 -2.7331 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7711 0.2370 -0.7981 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1365 0.2387 -1.0050 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6419 0.8285 -2.1528 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0149 -0.3280 -0.1057 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4800 -0.9102 1.0327 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3181 -1.4962 1.9731 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1175 -0.9048 1.2264 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5902 -1.4922 2.3730 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2182 -0.3364 0.3270 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9394 -0.3474 0.5379 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3924 0.5780 -0.6469 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7213 0.4531 -0.2214 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3005 0.1470 1.1774 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1059 1.2764 0.3684 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4213 -0.4078 -0.3090 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2183 -1.1585 2.6331 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8958 -0.9546 1.9157 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1159 1.3924 -3.3633 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8128 1.8336 -2.2328 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0876 -0.3394 -0.2452 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7707 -2.3871 1.8386 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3044 -0.9722 3.1806 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2480 1.0743 -1.5708 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4916 0.8702 -0.8647 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 8 10 1 0 10 11 2 0 10 12 1 0 12 13 2 0 13 14 1 0 13 15 1 0 15 16 2 0 16 17 1 0 16 18 1 0 18 19 1 0 18 20 2 0 20 21 1 0 6 22 1 0 22 23 2 0 23 3 1 0 21 7 1 0 20 12 1 0 1 24 1 0 1 25 1 0 1 26 1 0 4 27 1 0 5 28 1 0 9 29 1 0 14 30 1 0 15 31 1 0 17 32 1 0 19 33 1 0 22 34 1 0 23 35 1 0 M END

Standard InCHIKey	JENUDBBUZMVAMW-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H12O7/c1-22-8-4-2-7(3-5-8)15-14(21)13(20)11-9(17)6-10(18)12(19)16(11)23-15/h2-6,17-19,21H,1H3
SMILES	COC1=CC=C(C2=C(O)C(=O)C3=C(O)C=C(O)C(O)=C3O2)C=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	316.06	Volume:	300.063 ? Van der Waals volume.
Dense:	1.053	LogP:	1.998 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.099 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.048 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
TPSA:	120.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.423	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.442	Fsp³:	0.062
MCE-18:	19.0 ? 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:	1	PAINS Alert:	1
Colloidal aggregators:	0.836	Fluc inhibitor:	0.517 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.813 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.437 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.557	Promiscuous compounds:	0.933

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.553	MDCK Permeability:	-4.872
Pgp-inhibitor:	0.283	Pgp-substrate:	0.023
PAMPA:	0.508 ? 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):	0.324
20% Bioavailability (F20%):	0.268	30% Bioavailability (F30%):	0.913
50% Bioavailability (F50%):	0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.926
Plasma Protein Binding (PPB):	98.472%	Volume Distribution (VD):	-0.717
Fu:	1.111% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.969
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.952
BSEP inhibitor:	0.431

ADMET: Metabolism

CYP1A2-inhibitor:	0.262	CYP1A2-substrate:	0.015
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.519
CYP2C9-inhibitor:	0.763	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.923	CYP2D6-substrate:	0.144
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.003
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.991
HLM stability:	0.949 ? 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):

8.118

Half-life (T1/2):

1.448

ADMET: Toxicity

hERG Blockers:	0.061	hERG Blockers (10um):	0.419
Human Hepatotoxicity (H-HT):	0.409	Drug-induced Liver Injury (DILI):	0.936
AMES Toxicity:	0.697	Rat Oral Acute Toxicity:	0.438
Maximum Recommended Daily Dose:	0.565	Skin Sensitization:	0.612
Carcinogencity:	0.632	Eye Corrosion:	0.102
Eye Irritation:	0.986	Respiratory Toxicity:	0.735
Drug-induced Neurotoxicity:	0.014	Ototoxicity:	0.181
Hematotoxicity:	0.133	Drug-induced Nephrotoxicity:	0.066
Genotoxicity:	0.829	RPMI-8226 Immunitoxicity:	0.051
A549 Cytotoxicity:	0.461	Hek293 Cytotoxicity:	0.326
BCF:	1.11 ? 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:	3.972 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.764 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.386 ? 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
NPO21049	Pentagramma triangularis	Species	Pteridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17642	Chondropetalum paniculatum	Species	Restionaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17642	Chondropetalum paniculatum	Species	Restionaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21049	Pentagramma triangularis	Species	Pteridaceae	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 NPC580405 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	27556
0.1-0.2	18899
0.2-0.3	2579
0.3-0.4	656
0.4-0.5	129
0.5-0.6	25
0.6-0.7	6
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
0.7255	Intermediate Similarity	NPC225731
0.7059	Intermediate Similarity	NPC27208
0.6909	Remote Similarity	NPC201451
0.6909	Remote Similarity	NPC241838
0.623	Remote Similarity	NPC607815
0.6207	Remote Similarity	NPC86485
0.614	Remote Similarity	NPC44079
0.6032	Remote Similarity	NPC273538
0.5932	Remote Similarity	NPC32420
0.5932	Remote Similarity	NPC49824
0.5932	Remote Similarity	NPC480465
0.5833	Remote Similarity	NPC54394
0.5821	Remote Similarity	NPC605541
0.5593	Remote Similarity	NPC287979
0.5574	Remote Similarity	NPC200740
0.5574	Remote Similarity	NPC159103
0.55	Remote Similarity	NPC59951
0.55	Remote Similarity	NPC87125
0.55	Remote Similarity	NPC276905
0.55	Remote Similarity	NPC143799
0.55	Remote Similarity	NPC281207
0.55	Remote Similarity	NPC605146
0.55	Remote Similarity	NPC605755
0.5333	Remote Similarity	NPC152042
0.5323	Remote Similarity	NPC166753
0.5246	Remote Similarity	NPC50403
0.5246	Remote Similarity	NPC231772
0.5156	Remote Similarity	NPC133953
0.5085	Remote Similarity	NPC179271
0.5082	Remote Similarity	NPC219330
0.5082	Remote Similarity	NPC98661
0.5082	Remote Similarity	NPC262094
0.5082	Remote Similarity	NPC600177

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC580405 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4856
0.1-0.2	4207
0.2-0.3	82
0.3-0.4	3
0.4-0.5	1
0.5-0.6	0
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	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.6032	Remote Similarity	NPD4378	Phase 3

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