NPASS Compound

Natural Product: NPC574493

Natural Product ID	NPC574493
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5,7-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4H-chromen-4-one
IUPAC Name	5,7-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)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 46 48 0 0 0 0 0 0 0 0999 V2000 6.1668 0.0390 3.0824 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1052 -0.1427 1.7009 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9406 -0.0678 0.9467 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7106 0.1955 1.4786 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5805 0.2627 0.7072 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6842 0.0555 -0.6712 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4691 0.1299 -1.4818 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5175 -0.0625 -2.8271 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3563 0.0060 -3.6218 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4170 -0.1738 -4.8619 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8078 0.2781 -2.9383 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9891 0.3615 -3.6467 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9510 0.1662 -5.0246 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1582 0.6332 -2.9719 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1826 0.8254 -1.5996 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3938 1.0956 -0.9805 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0139 0.7454 -0.8816 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9494 0.9370 0.5890 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4428 -0.2222 1.3633 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4140 -0.1538 2.2546 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1180 1.1115 2.5756 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8196 -1.4178 2.9736 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8209 0.4679 -1.5726 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2982 0.3891 -0.9001 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9133 -0.2068 -1.1973 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0524 -0.2716 -0.3995 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0245 -0.5747 3.4663 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2649 -0.2666 3.6327 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3994 1.0810 3.3812 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6483 0.3531 2.5464 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5897 0.4751 1.1352 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4418 -0.2731 -3.3296 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9932 -0.7482 -5.4498 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1031 0.7042 -3.5085 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2291 0.5176 -1.1420 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9075 1.2124 0.8593 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5913 1.8349 0.8073 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9705 -1.1759 1.1782 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4978 1.7424 3.2390 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0585 0.8686 3.1342 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4205 1.6421 1.6765 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5105 -1.9626 2.3192 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3600 -1.1710 3.9074 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9051 -1.9550 3.2317 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0339 -0.3765 -2.2846 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9940 -0.4855 -0.8955 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 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 12 14 1 0 14 15 2 0 15 16 1 0 15 17 1 0 17 18 1 0 18 19 1 0 19 20 2 3 20 21 1 0 20 22 1 0 17 23 2 0 23 24 1 0 6 25 1 0 25 26 2 0 26 3 1 0 24 7 1 0 23 11 1 0 1 27 1 0 1 28 1 0 1 29 1 0 4 30 1 0 5 31 1 0 8 32 1 0 13 33 1 0 14 34 1 0 16 35 1 0 18 36 1 0 18 37 1 0 19 38 1 0 21 39 1 0 21 40 1 0 21 41 1 0 22 42 1 0 22 43 1 0 22 44 1 0 25 45 1 0 26 46 1 0 M END

Standard InCHIKey	XPDHBXBLKMCNKB-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C21H20O5/c1-12(2)4-9-15-16(22)10-17(23)20-18(24)11-19(26-21(15)20)13-5-7-14(25-3)8-6-13/h4-8,10-11,22-23H,9H2,1-3H3
SMILES	COC1=CC=C(C2=CC(=O)C3=C(O)C=C(O)C(CC=C(C)C)=C3O2)C=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	352.13	Volume:	366.326 ? Van der Waals volume.
Dense:	0.961	LogP:	4.479 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.614 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.919 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	19.0
TPSA:	79.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.681	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.562	Fsp³:	0.19
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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.907	Fluc inhibitor:	0.69 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.993 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.853 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.241	Promiscuous compounds:	0.166

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.945	MDCK Permeability:	-4.67
Pgp-inhibitor:	0.742	Pgp-substrate:	0.167
PAMPA:	0.094 ? 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):	0.141
20% Bioavailability (F20%):	0.724	30% Bioavailability (F30%):	0.926
50% Bioavailability (F50%):	0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.91
Plasma Protein Binding (PPB):	96.746%	Volume Distribution (VD):	0.126
Fu:	2.777% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.988
OATP1B3 inhibitor:	0.974	BCRP inhibitor:	0.887
BSEP inhibitor:	0.933

ADMET: Metabolism

CYP1A2-inhibitor:	0.016	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.99	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.593	CYP2C9-substrate:	0.988
CYP2D6-inhibitor:	0.999	CYP2D6-substrate:	0.912
CYP3A4-inhibitor:	0.024	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

4.86

Half-life (T1/2):

1.107

ADMET: Toxicity

hERG Blockers:	0.057	hERG Blockers (10um):	0.506
Human Hepatotoxicity (H-HT):	0.467	Drug-induced Liver Injury (DILI):	0.92
AMES Toxicity:	0.745	Rat Oral Acute Toxicity:	0.678
Maximum Recommended Daily Dose:	0.691	Skin Sensitization:	0.74
Carcinogencity:	0.654	Eye Corrosion:	0.008
Eye Irritation:	0.928	Respiratory Toxicity:	0.973
Drug-induced Neurotoxicity:	0.112	Ototoxicity:	0.128
Hematotoxicity:	0.151	Drug-induced Nephrotoxicity:	0.173
Genotoxicity:	0.969	RPMI-8226 Immunitoxicity:	0.075
A549 Cytotoxicity:	0.275	Hek293 Cytotoxicity:	0.632
BCF:	1.839 ? 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:	4.66 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.096 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.508 ? 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
NPO772	Bosistoa floydii	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO772	Bosistoa floydii	Species	Rutaceae	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 NPC574493 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	19209
0.1-0.2	25397
0.2-0.3	4199
0.3-0.4	813
0.4-0.5	199
0.5-0.6	29
0.6-0.7	3
0.7-0.8	1
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
0.7759	Intermediate Similarity	NPC606140
0.7627	Intermediate Similarity	NPC220062
0.7419	Intermediate Similarity	NPC273538
0.7213	Intermediate Similarity	NPC88804
0.7121	Intermediate Similarity	NPC471982
0.7049	Intermediate Similarity	NPC482025
0.6875	Remote Similarity	NPC216978
0.6615	Remote Similarity	NPC601414
0.6081	Remote Similarity	NPC471985
0.5968	Remote Similarity	NPC600177
0.5873	Remote Similarity	NPC231772
0.5679	Remote Similarity	NPC278419
0.5679	Remote Similarity	NPC179198
0.5625	Remote Similarity	NPC482938
0.5588	Remote Similarity	NPC482709
0.5538	Remote Similarity	NPC603662
0.5522	Remote Similarity	NPC9117
0.5522	Remote Similarity	NPC63187
0.5479	Remote Similarity	NPC604255
0.5479	Remote Similarity	NPC605541
0.5469	Remote Similarity	NPC52611
0.5469	Remote Similarity	NPC29353
0.5342	Remote Similarity	NPC241100
0.5278	Remote Similarity	NPC479160
0.5231	Remote Similarity	NPC274327
0.5231	Remote Similarity	NPC156222
0.5211	Remote Similarity	NPC293053
0.5205	Remote Similarity	NPC130589
0.52	Remote Similarity	NPC610891
0.5152	Remote Similarity	NPC184136
0.5152	Remote Similarity	NPC176775
0.5152	Remote Similarity	NPC57030
0.5152	Remote Similarity	NPC145379
0.5152	Remote Similarity	NPC604462
0.5143	Remote Similarity	NPC607815
0.5139	Remote Similarity	NPC36852
0.5072	Remote Similarity	NPC610914
0.5068	Remote Similarity	NPC482019

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC574493 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3144
0.1-0.2	5854
0.2-0.3	141
0.3-0.4	8
0.4-0.5	2
0.5-0.6	0
0.6-0.7	0
0.7-0.8	1
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
0.7419	Intermediate 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