NPASS Compound

Natural Product: NPC561039

Natural Product ID	NPC561039
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{S})-6-[(2~{R})-5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-chroman-6-yl]-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one
IUPAC Name	(2~{S})-6-[(2~{R})-5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-chroman-6-yl]-5,7-dihydroxy-2-(4-hydroxyphenyl)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 62 67 0 0 0 0 0 0 0 0999 V2000 2.9644 -2.8524 0.7493 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6058 -1.7702 0.7271 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0566 -1.8234 0.9216 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6880 -0.4862 1.1595 C 0 0 1 0 0 0 0 0 0 0 0 0 6.9619 -0.4359 0.4014 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9516 -0.1597 -0.9694 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1028 -0.1049 -1.7021 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3221 -0.3230 -1.1028 C 0 0 0 0 0 0 0 0 0 0 0 0 10.5159 -0.2758 -1.8139 O 0 0 0 0 0 0 0 0 0 0 0 0 9.3775 -0.6014 0.2610 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1857 -0.6510 0.9841 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9135 0.6039 0.7862 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5687 0.6460 0.5485 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8860 1.8503 0.3435 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5319 1.8095 0.1100 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8582 3.0291 -0.0945 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7968 0.6426 0.0648 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6254 0.6271 -0.1827 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0812 0.5344 -1.4876 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1591 0.4592 -2.5216 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4262 0.5150 -1.7870 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3766 0.5887 -0.7756 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7231 0.5740 -1.0066 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7389 1.0249 -0.1631 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.9670 0.1878 -0.2500 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2240 0.7467 -0.3373 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.3728 -0.0052 -0.4183 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2588 -1.3900 -0.4117 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.4212 -2.1432 -0.4937 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.0198 -1.9884 -0.3257 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8898 -1.1834 -0.2460 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3571 1.1682 1.2712 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9600 0.7574 1.5662 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6321 0.4608 2.7434 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9359 0.6817 0.5340 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5917 0.6987 0.7986 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1933 0.7926 2.1183 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4945 -0.5324 0.2704 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8507 -1.7674 0.2460 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8644 -0.5401 0.5101 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4916 -2.3303 0.0155 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2911 -2.5005 1.7794 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9207 -0.3821 2.2540 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9734 0.0060 -1.4040 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0728 0.1093 -2.7565 H 0 0 0 0 0 0 0 0 0 0 0 0 11.1679 0.4569 -1.5199 H 0 0 0 0 0 0 0 0 0 0 0 0 10.3319 -0.7717 0.7280 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1951 -0.8681 2.0610 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4760 2.7505 0.3823 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3158 3.7956 -0.6007 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3021 1.1100 -3.3021 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7829 0.4435 -2.7928 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0213 2.0542 -0.5354 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3130 1.8240 -0.3426 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3623 0.4219 -0.4872 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.2397 -1.8057 -0.0067 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9886 -3.0680 -0.3245 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9147 -1.6426 -0.1784 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4333 2.2365 1.6302 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0472 0.5987 1.9340 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2328 0.0221 2.7725 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1410 -1.8249 0.4402 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 4 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 15 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 19 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 28 30 1 0 30 31 2 0 24 32 1 0 32 33 1 0 33 34 2 0 33 35 1 0 35 36 2 0 36 37 1 0 17 38 1 0 38 39 1 0 38 40 2 0 40 2 1 0 11 5 1 0 40 13 1 0 36 18 1 0 35 22 1 0 31 25 1 0 3 41 1 0 3 42 1 0 4 43 1 1 6 44 1 0 7 45 1 0 9 46 1 0 10 47 1 0 11 48 1 0 14 49 1 0 16 50 1 0 20 51 1 0 21 52 1 0 24 53 1 6 26 54 1 0 27 55 1 0 29 56 1 0 30 57 1 0 31 58 1 0 32 59 1 0 32 60 1 0 37 61 1 0 39 62 1 0 M END

Standard InCHIKey	LJHQEYHSSFSFCF-SZPZYZBQSA-N
Standard InCHI	InChI=1S/C30H22O10/c31-15-5-1-13(2-6-15)21-9-17(33)25-23(39-21)11-19(35)27(29(25)37)28-20(36)12-24-26(30(28)38)18(34)10-22(40-24)14-3-7-16(32)8-4-14/h1-8,11-12,21-22,31-32,35-38H,9-10H2/t21-,22+
SMILES	O=C1C[C@@H](C2=CC=C(O)C=C2)OC2=CC(O)=C(C3=C(O)C=C4O[C@@H](C5=CC=C(O)C=C5)CC(=O)C4=C3O)C(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	542.12	Volume:	527.089 ? Van der Waals volume.
Dense:	1.029	LogP:	3.854 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.231 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.949 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	36.0
TPSA:	173.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	6.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.207	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.758	Fsp³:	0.133
MCE-18:	116.471 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.987	Fluc inhibitor:	0.616 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.361 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.603 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.457	Promiscuous compounds:	0.093

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.67	MDCK Permeability:	-4.864
Pgp-inhibitor:	0.969	Pgp-substrate:	0.015
PAMPA:	0.903 ? 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):	0.0
20% Bioavailability (F20%):	0.0	30% Bioavailability (F30%):	0.378
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.998
Plasma Protein Binding (PPB):	96.435%	Volume Distribution (VD):	-0.009
Fu:	5.128% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.965
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.985
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.811
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.999
CYP2C9-inhibitor:	0.032	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.085	CYP2D6-substrate:	0.145
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.415
HLM stability:	0.967 ? 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):

3.266

Half-life (T1/2):

2.102

ADMET: Toxicity

hERG Blockers:	0.074	hERG Blockers (10um):	0.469
Human Hepatotoxicity (H-HT):	0.877	Drug-induced Liver Injury (DILI):	0.366
AMES Toxicity:	0.704	Rat Oral Acute Toxicity:	0.761
Maximum Recommended Daily Dose:	0.962	Skin Sensitization:	0.95
Carcinogencity:	0.267	Eye Corrosion:	0.0
Eye Irritation:	0.987	Respiratory Toxicity:	0.581
Drug-induced Neurotoxicity:	0.65	Ototoxicity:	0.454
Hematotoxicity:	0.031	Drug-induced Nephrotoxicity:	0.82
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.366
A549 Cytotoxicity:	0.985	Hek293 Cytotoxicity:	0.963
BCF:	1.184 ? 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:	4.319 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.955 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.592 ? 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
NPO48483	Rhus succedanea	Species	Anacardiaceae	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 NPC561039 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	23665
0.1-0.2	21941
0.2-0.3	3518
0.3-0.4	503
0.4-0.5	161
0.5-0.6	52
0.6-0.7	8
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC300668
0.7778	Intermediate Similarity	NPC134171
0.7119	Intermediate Similarity	NPC51760
0.68	Remote Similarity	NPC32441
0.68	Remote Similarity	NPC79943
0.6538	Remote Similarity	NPC324386
0.6415	Remote Similarity	NPC606248
0.6226	Remote Similarity	NPC329203
0.6226	Remote Similarity	NPC222342
0.62	Remote Similarity	NPC329225
0.62	Remote Similarity	NPC147686
0.5962	Remote Similarity	NPC225153
0.5962	Remote Similarity	NPC479876
0.5915	Remote Similarity	NPC604941
0.5818	Remote Similarity	NPC321011
0.5818	Remote Similarity	NPC294852
0.5818	Remote Similarity	NPC469764
0.5818	Remote Similarity	NPC188679
0.5818	Remote Similarity	NPC475267
0.5625	Remote Similarity	NPC611447
0.5574	Remote Similarity	NPC470135
0.5556	Remote Similarity	NPC243083
0.5556	Remote Similarity	NPC13768
0.5556	Remote Similarity	NPC287246
0.5556	Remote Similarity	NPC603284
0.5455	Remote Similarity	NPC1612
0.5455	Remote Similarity	NPC183959
0.5455	Remote Similarity	NPC167624
0.5455	Remote Similarity	NPC166482
0.541	Remote Similarity	NPC69674
0.537	Remote Similarity	NPC476480
0.537	Remote Similarity	NPC84585
0.5357	Remote Similarity	NPC274784
0.5357	Remote Similarity	NPC20709
0.5323	Remote Similarity	NPC220998
0.5316	Remote Similarity	NPC485523
0.5273	Remote Similarity	NPC295261
0.5273	Remote Similarity	NPC296490
0.5273	Remote Similarity	NPC204515
0.5263	Remote Similarity	NPC485881
0.5263	Remote Similarity	NPC210084
0.5246	Remote Similarity	NPC39329
0.5246	Remote Similarity	NPC51032
0.5224	Remote Similarity	NPC228504
0.5179	Remote Similarity	NPC312391
0.5167	Remote Similarity	NPC236637
0.5161	Remote Similarity	NPC477841
0.5152	Remote Similarity	NPC69531
0.5147	Remote Similarity	NPC472629
0.5091	Remote Similarity	NPC182421
0.5088	Remote Similarity	NPC255106
0.5088	Remote Similarity	NPC482119
0.5088	Remote Similarity	NPC235165
0.5088	Remote Similarity	NPC482120
0.5082	Remote Similarity	NPC169591
0.5082	Remote Similarity	NPC298223
0.5082	Remote Similarity	NPC604412
0.5079	Remote Similarity	NPC109223
0.5079	Remote Similarity	NPC470131
0.5079	Remote Similarity	NPC470133
0.5079	Remote Similarity	NPC470132
0.5079	Remote Similarity	NPC10937
0.5072	Remote Similarity	NPC488556

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC561039 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3995
0.1-0.2	5016
0.2-0.3	129
0.3-0.4	3
0.4-0.5	4
0.5-0.6	1
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	Drug ID	Developmental Stage
0.68	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.62	Remote Similarity	NPD1549	Phase 2
0.5556	Remote Similarity	NPD1550	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