NPASS Compound

Natural Product: NPC585185

Natural Product ID	NPC585185
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-(2,4-dihydroxyphenyl)-5,7-dihydroxy-chroman-4-one
IUPAC Name	(2~{R})-2-(2,4-dihydroxyphenyl)-5,7-dihydroxy-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 33 35 0 0 0 0 0 0 0 0999 V2000 1.9863 -3.0676 -0.4082 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4016 -1.9954 -0.1412 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0453 -1.9996 0.0936 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5388 -0.9148 0.9993 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7030 -0.2000 0.4184 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5194 0.9078 -0.3786 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6100 1.5623 -0.9117 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8986 1.1354 -0.6678 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0064 1.7936 -1.2046 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0709 0.0243 0.1322 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9807 -0.6456 0.6765 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1109 -1.7654 1.4850 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4229 0.0543 1.3230 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6198 0.2619 0.6960 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3325 1.4393 0.7743 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5316 1.5934 0.1230 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2011 2.7977 0.2388 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0580 0.5510 -0.6388 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3687 -0.6264 -0.7312 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8460 -1.7127 -1.4824 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1546 -0.7747 -0.0684 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3315 -2.9991 0.4973 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5730 -1.9397 -0.8998 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8455 -1.3812 1.9741 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5083 1.2575 -0.5806 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4827 2.4398 -1.5440 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2950 2.6894 -0.8407 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0561 -0.3675 0.3662 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7048 -2.5133 1.1346 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9535 2.2663 1.3556 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7395 3.6606 0.4491 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9991 0.6437 -1.1621 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6657 -2.1752 -1.0770 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 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 11 12 1 0 4 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 16 18 2 0 18 19 1 0 19 20 1 0 19 21 2 0 21 2 1 0 11 5 1 0 21 14 1 0 3 22 1 0 3 23 1 0 4 24 1 1 6 25 1 0 7 26 1 0 9 27 1 0 10 28 1 0 12 29 1 0 15 30 1 0 17 31 1 0 18 32 1 0 20 33 1 0 M END

Standard InCHIKey	QBLQLKNOKUHRCH-CYBMUJFWSA-N
Standard InCHI	InChI=1S/C15H12O6/c16-7-1-2-9(10(18)3-7)13-6-12(20)15-11(19)4-8(17)5-14(15)21-13/h1-5,13,16-19H,6H2/t13-/m1/s1
SMILES	O=C1C[C@H](C2=CC=C(O)C=C2O)OC2=CC(O)=CC(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	288.06	Volume:	276.613 ? Van der Waals volume.
Dense:	1.041	LogP:	2.151 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.329 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.429 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	107.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.641	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.045	Fsp³:	0.133
MCE-18:	58.235 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.666	Fluc inhibitor:	0.683 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.303 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.217 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.524	Promiscuous compounds:	0.073

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.19	MDCK Permeability:	-4.801
Pgp-inhibitor:	0.225	Pgp-substrate:	0.181
PAMPA:	0.138 ? 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):	0.001
20% Bioavailability (F20%):	0.081	30% Bioavailability (F30%):	0.948
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.776
Plasma Protein Binding (PPB):	92.158%	Volume Distribution (VD):	-0.19
Fu:	9.652% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.968
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.987
BSEP inhibitor:	0.424

ADMET: Metabolism

CYP1A2-inhibitor:	0.753	CYP1A2-substrate:	0.763
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.879
CYP2C9-inhibitor:	0.043	CYP2C9-substrate:	0.111
CYP2D6-inhibitor:	0.725	CYP2D6-substrate:	0.994
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.943
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.994
HLM stability:	0.959 ? 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):

3.297

Half-life (T1/2):

1.87

ADMET: Toxicity

hERG Blockers:	0.083	hERG Blockers (10um):	0.5
Human Hepatotoxicity (H-HT):	0.722	Drug-induced Liver Injury (DILI):	0.374
AMES Toxicity:	0.676	Rat Oral Acute Toxicity:	0.702
Maximum Recommended Daily Dose:	0.886	Skin Sensitization:	0.909
Carcinogencity:	0.335	Eye Corrosion:	0.075
Eye Irritation:	0.997	Respiratory Toxicity:	0.942
Drug-induced Neurotoxicity:	0.527	Ototoxicity:	0.291
Hematotoxicity:	0.034	Drug-induced Nephrotoxicity:	0.315
Genotoxicity:	0.991	RPMI-8226 Immunitoxicity:	0.137
A549 Cytotoxicity:	0.821	Hek293 Cytotoxicity:	0.834
BCF:	1.244 ? 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:	3.732 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.474 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.859 ? 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
NPO5495	Broussonetia papyrifera	Species	Moraceae	Eukaryota	n.a.	root	n.a.	PMID[11395279]
NPO5495	Broussonetia papyrifera	Species	Moraceae	Eukaryota	whole plants	Shawnee National Forest, Harrisburg, IL, US	n.a.	PMID[11678652]
NPO5495	Broussonetia papyrifera	Species	Moraceae	Eukaryota	whole plants	n.a.	n.a.	PMID[11678652]
NPO10498	Artocarpus dadah	Species	Moraceae	Eukaryota	bark and twigs	Tewah, Central Kalimantan, Indonesia (N 38 57.003; W 094 44.767)	1999-Oct	PMID[11858749]
NPO5495	Broussonetia papyrifera	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12419367]
NPO5495	Broussonetia papyrifera	Species	Moraceae	Eukaryota	leaves	Kaohsiung, Taiwan	2006-SEP	PMID[18986201]
NPO5495	Broussonetia papyrifera	Species	Moraceae	Eukaryota	Fruits	n.a.	n.a.	PMID[19296617]
NPO5495	Broussonetia papyrifera	Species	Moraceae	Eukaryota	n.a.	formosan	n.a.	PMID[8864236]
NPO5495	Broussonetia papyrifera	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9358644]
NPO15163	Euphorbia stepposa	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO50654	Cudrania cochinchinensis var. gerontogea	Genus	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10498	Artocarpus dadah	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24383	Ficus formosana	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5495	Broussonetia papyrifera	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10498	Artocarpus dadah	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5495	Broussonetia papyrifera	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10498	Artocarpus dadah	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5495	Broussonetia papyrifera	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15163	Euphorbia stepposa	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO5495	Broussonetia papyrifera	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO5495	Broussonetia papyrifera	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO24383	Ficus formosana	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15163	Euphorbia stepposa	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5495	Broussonetia papyrifera	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10498	Artocarpus dadah	Species	Moraceae	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 NPC585185 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	26659
0.1-0.2	19445
0.2-0.3	2851
0.3-0.4	635
0.4-0.5	178
0.5-0.6	55
0.6-0.7	10
0.7-0.8	2
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC295261
1.0	High Similarity	NPC296490
0.8261	Intermediate Similarity	NPC107586
0.7826	Intermediate Similarity	NPC32441
0.7826	Intermediate Similarity	NPC79943
0.7551	Intermediate Similarity	NPC310135
0.7447	Intermediate Similarity	NPC472460
0.7083	Intermediate Similarity	NPC243083
0.7083	Intermediate Similarity	NPC13768
0.7083	Intermediate Similarity	NPC287246
0.7083	Intermediate Similarity	NPC12296
0.7	Intermediate Similarity	NPC321011
0.7	Intermediate Similarity	NPC294852
0.7	Intermediate Similarity	NPC188679
0.6875	Remote Similarity	NPC182421
0.68	Remote Similarity	NPC274784
0.68	Remote Similarity	NPC20709
0.6491	Remote Similarity	NPC223500
0.6481	Remote Similarity	NPC236637
0.6471	Remote Similarity	NPC338131
0.6415	Remote Similarity	NPC302950
0.614	Remote Similarity	NPC477841
0.6034	Remote Similarity	NPC109223
0.6034	Remote Similarity	NPC10937
0.5965	Remote Similarity	NPC324436
0.5965	Remote Similarity	NPC78
0.5962	Remote Similarity	NPC279417
0.5962	Remote Similarity	NPC49130
0.5806	Remote Similarity	NPC611447
0.5789	Remote Similarity	NPC258630
0.5738	Remote Similarity	NPC470647
0.5652	Remote Similarity	NPC105584
0.5625	Remote Similarity	NPC96408
0.5625	Remote Similarity	NPC610511
0.5606	Remote Similarity	NPC58805
0.5574	Remote Similarity	NPC108456
0.5556	Remote Similarity	NPC329203
0.5556	Remote Similarity	NPC324386
0.5556	Remote Similarity	NPC222342
0.5556	Remote Similarity	NPC88964
0.55	Remote Similarity	NPC17170
0.5484	Remote Similarity	NPC485620
0.5472	Remote Similarity	NPC201227
0.5472	Remote Similarity	NPC258474
0.541	Remote Similarity	NPC106976
0.541	Remote Similarity	NPC285555
0.5397	Remote Similarity	NPC312973
0.5397	Remote Similarity	NPC475790
0.5385	Remote Similarity	NPC328164
0.537	Remote Similarity	NPC4743
0.5323	Remote Similarity	NPC174953
0.5323	Remote Similarity	NPC85121
0.5312	Remote Similarity	NPC278249
0.5312	Remote Similarity	NPC223812
0.5312	Remote Similarity	NPC69531
0.5306	Remote Similarity	NPC482958
0.5303	Remote Similarity	NPC473016
0.5303	Remote Similarity	NPC279650
0.5273	Remote Similarity	NPC300668
0.5238	Remote Similarity	NPC134783
0.5231	Remote Similarity	NPC131579
0.5231	Remote Similarity	NPC485613
0.5192	Remote Similarity	NPC329225
0.5192	Remote Similarity	NPC147686
0.5185	Remote Similarity	NPC264083
0.5185	Remote Similarity	NPC603284
0.5179	Remote Similarity	NPC469764
0.5179	Remote Similarity	NPC606248
0.5167	Remote Similarity	NPC91560
0.5161	Remote Similarity	NPC134171
0.5156	Remote Similarity	NPC470890
0.5156	Remote Similarity	NPC200761
0.5094	Remote Similarity	NPC482472
0.5091	Remote Similarity	NPC62290
0.5091	Remote Similarity	NPC142731
0.5091	Remote Similarity	NPC326506
0.5077	Remote Similarity	NPC473990
0.5075	Remote Similarity	NPC485617
0.5072	Remote Similarity	NPC67396

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC585185 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4696
0.1-0.2	4340
0.2-0.3	100
0.3-0.4	10
0.4-0.5	0
0.5-0.6	1
0.6-0.7	1
0.7-0.8	2
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
0.7826	Intermediate Similarity	NPD1552	Clinical (unspecified phase)
0.7083	Intermediate Similarity	NPD1550	Phase 2
0.6415	Remote Similarity	NPD1934	Phase 0
0.5192	Remote Similarity	NPD1549	Phase 2

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