NPASS Compound

Natural Product: NPC548042

Natural Product ID	NPC548042
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{R})-2-(3,4-dihydroxyphenyl)-5-hydroxy-7-methoxy-8-(3-methylbut-2-enyl)chroman-4-one
IUPAC Name	(2~{R})-2-(3,4-dihydroxyphenyl)-5-hydroxy-7-methoxy-8-(3-methylbut-2-enyl)chroman-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 49 51 0 0 0 0 0 0 0 0999 V2000 -5.0236 0.5867 -0.9254 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9477 0.6485 -0.0127 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6778 1.0002 -0.4686 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5051 1.2812 -1.8133 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2442 1.6290 -2.2546 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0428 1.9159 -3.6003 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2249 1.6779 -1.3336 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1259 2.0580 -1.7942 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4564 1.9603 -2.9906 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0610 2.5599 -0.7629 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0183 1.6166 0.4164 C 0 0 2 0 0 0 0 0 0 0 0 0 2.7623 0.3796 0.1864 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2101 -0.7185 -0.4338 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0057 -1.8448 -0.6106 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3167 -1.9259 -0.2007 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0922 -3.0679 -0.3907 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8562 -0.8111 0.4218 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1694 -0.7972 0.8698 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0745 0.3081 0.6007 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7135 1.4747 0.8777 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3532 1.4062 0.0099 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6379 1.0527 0.4558 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8544 0.7863 1.8746 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0300 -0.5857 2.3296 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0348 -1.7204 1.7127 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2527 -2.9811 2.5259 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8443 -1.8931 0.2719 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7861 0.0255 -1.8518 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8799 0.0727 -0.4371 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3297 1.6130 -1.2604 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3082 1.2428 -2.5378 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9610 2.9010 -3.8355 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7993 3.6017 -0.4516 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1052 2.5286 -1.1691 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5876 2.1930 1.2366 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1990 -0.7488 -0.7864 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5984 -2.7244 -1.0957 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7483 -3.7261 -1.0903 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5689 0.0046 1.2992 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5459 1.1703 1.1000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7307 1.3787 2.2795 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9784 1.2255 2.4613 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1986 -0.6977 3.4593 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3372 -3.5927 2.3477 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3334 -2.7590 3.6014 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1002 -3.5656 2.1229 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0327 -1.3153 -0.1727 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5515 -2.9922 0.1105 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8136 -1.8318 -0.2913 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 1 0 5 7 2 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 15 17 1 0 17 18 1 0 17 19 2 0 11 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 24 25 2 3 25 26 1 0 25 27 1 0 22 3 1 0 21 7 1 0 19 12 1 0 1 28 1 0 1 29 1 0 1 30 1 0 4 31 1 0 6 32 1 0 10 33 1 0 10 34 1 0 11 35 1 1 13 36 1 0 14 37 1 0 16 38 1 0 18 39 1 0 19 40 1 0 23 41 1 0 23 42 1 0 24 43 1 0 26 44 1 0 26 45 1 0 26 46 1 0 27 47 1 0 27 48 1 0 27 49 1 0 M END

Standard InCHIKey	QTHZKQQTHZVUHQ-GOSISDBHSA-N
Standard InCHI	InChI=1S/C21H22O6/c1-11(2)4-6-13-19(26-3)10-17(25)20-16(24)9-18(27-21(13)20)12-5-7-14(22)15(23)8-12/h4-5,7-8,10,18,22-23,25H,6,9H2,1-3H3/t18-/m1/s1
SMILES	COC1=CC(O)=C2C(=O)C[C@H](C3=CC=C(O)C(O)=C3)OC2=C1CC=C(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	370.14	Volume:	377.752 ? Van der Waals volume.
Dense:	0.98	LogP:	4.199 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.484 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.337 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	19.0
TPSA:	96.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.555	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.299	Fsp³:	0.286
MCE-18:	62.963 ? 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:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.753	Fluc inhibitor:	0.675 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.638 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.501 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.286	Promiscuous compounds:	0.143

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.984	MDCK Permeability:	-4.755
Pgp-inhibitor:	0.951	Pgp-substrate:	0.004
PAMPA:	0.151 ? 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):	0.029
20% Bioavailability (F20%):	0.439	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.927
Plasma Protein Binding (PPB):	95.81%	Volume Distribution (VD):	0.025
Fu:	3.951% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.999
BSEP inhibitor:	0.804

ADMET: Metabolism

CYP1A2-inhibitor:	0.022	CYP1A2-substrate:	0.993
CYP2C19-inhibitor:	0.947	CYP2C19-substrate:	0.859
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.015	CYP2D6-substrate:	0.98
CYP3A4-inhibitor:	0.004	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
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):

13.453

Half-life (T1/2):

1.659

ADMET: Toxicity

hERG Blockers:	0.079	hERG Blockers (10um):	0.573
Human Hepatotoxicity (H-HT):	0.687	Drug-induced Liver Injury (DILI):	0.536
AMES Toxicity:	0.809	Rat Oral Acute Toxicity:	0.778
Maximum Recommended Daily Dose:	0.599	Skin Sensitization:	0.973
Carcinogencity:	0.517	Eye Corrosion:	0.0
Eye Irritation:	0.939	Respiratory Toxicity:	0.42
Drug-induced Neurotoxicity:	0.458	Ototoxicity:	0.759
Hematotoxicity:	0.221	Drug-induced Nephrotoxicity:	0.691
Genotoxicity:	0.979	RPMI-8226 Immunitoxicity:	0.058
A549 Cytotoxicity:	0.805	Hek293 Cytotoxicity:	0.496
BCF:	1.81 ? 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:	4.629 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.255 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.524 ? 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
NPO63406	Flourensia heterolepis	Genus	Asteraceae	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

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 NPC548042 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	18379
0.1-0.2	24754
0.2-0.3	5669
0.3-0.4	733
0.4-0.5	250
0.5-0.6	60
0.6-0.7	4
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8421	Intermediate Similarity	NPC220998
0.7049	Intermediate Similarity	NPC156190
0.6406	Remote Similarity	NPC610133
0.6061	Remote Similarity	NPC76338
0.6061	Remote Similarity	NPC250242
0.6	Remote Similarity	NPC328164
0.597	Remote Similarity	NPC291878
0.5915	Remote Similarity	NPC213896
0.5909	Remote Similarity	NPC480990
0.5846	Remote Similarity	NPC107572
0.5846	Remote Similarity	NPC32739
0.5758	Remote Similarity	NPC148757
0.5714	Remote Similarity	NPC35038
0.5672	Remote Similarity	NPC66515
0.5652	Remote Similarity	NPC161506
0.5645	Remote Similarity	NPC321011
0.5645	Remote Similarity	NPC294852
0.5645	Remote Similarity	NPC188679
0.5588	Remote Similarity	NPC125855
0.5588	Remote Similarity	NPC480158
0.5556	Remote Similarity	NPC484416
0.5541	Remote Similarity	NPC261063
0.5522	Remote Similarity	NPC69674
0.5522	Remote Similarity	NPC175504
0.5467	Remote Similarity	NPC321779
0.5455	Remote Similarity	NPC76372
0.5455	Remote Similarity	NPC37496
0.5441	Remote Similarity	NPC17170
0.5441	Remote Similarity	NPC109223
0.5441	Remote Similarity	NPC10937
0.5417	Remote Similarity	NPC125894
0.5417	Remote Similarity	NPC142405
0.5405	Remote Similarity	NPC479210
0.5397	Remote Similarity	NPC192083
0.5385	Remote Similarity	NPC259685
0.5373	Remote Similarity	NPC1089
0.5373	Remote Similarity	NPC39329
0.5373	Remote Similarity	NPC51032
0.5362	Remote Similarity	NPC106976
0.5294	Remote Similarity	NPC149026
0.5294	Remote Similarity	NPC265040
0.5294	Remote Similarity	NPC102540
0.5294	Remote Similarity	NPC250214
0.5286	Remote Similarity	NPC608140
0.5263	Remote Similarity	NPC83357
0.5238	Remote Similarity	NPC194432
0.5224	Remote Similarity	NPC164980
0.5224	Remote Similarity	NPC169591
0.5224	Remote Similarity	NPC298223
0.5224	Remote Similarity	NPC604412
0.5217	Remote Similarity	NPC68104
0.5211	Remote Similarity	NPC36217
0.52	Remote Similarity	NPC224851
0.5195	Remote Similarity	NPC312273
0.5147	Remote Similarity	NPC324436
0.5147	Remote Similarity	NPC78
0.5147	Remote Similarity	NPC150408
0.5147	Remote Similarity	NPC306829
0.5147	Remote Similarity	NPC476342
0.5079	Remote Similarity	NPC1612
0.5079	Remote Similarity	NPC183959
0.5077	Remote Similarity	NPC474208
0.5072	Remote Similarity	NPC221432
0.5072	Remote Similarity	NPC257097
0.5065	Remote Similarity	NPC192686
0.5065	Remote Similarity	NPC278778

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC548042 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3351
0.1-0.2	5641
0.2-0.3	149
0.3-0.4	4
0.4-0.5	4
0.5-0.6	1
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
0.5397	Remote Similarity	NPD2393	Clinical (unspecified phase)

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