NPASS Compound

Natural Product: NPC6511

Natural Product ID	NPC6511
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Erythraddison A
IUPAC Name	5-hydroxy-10-(hydroxymethyl)-7-(4-hydroxyphenyl)-2,2-dimethylpyrano[3,2-g]chromen-6-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1271772
PubChem CID	50899658
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0001612] Isoflavans [CHEMONTID:0001827] Isoflavanones [CHEMONTID:0003526] 6-prenylated isoflavanones

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 45 48 0 0 0 0 0 0 0 0999 V2000 -5.4480 0.7250 0.9957 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6715 0.1642 -0.2138 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6961 -0.7000 -0.9459 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2755 1.3243 -1.0026 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0142 1.6273 -1.1988 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9308 0.8294 -0.6455 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6086 1.1222 -0.8328 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3864 0.3163 -0.2739 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7227 0.5746 -0.4366 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0259 1.5890 -1.1257 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6438 -0.2576 0.1401 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1903 -1.3370 0.8718 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9209 -1.5758 1.0216 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0384 -0.7945 0.4802 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2979 -1.0714 0.6558 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6887 -2.2571 1.4538 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5189 -3.4306 0.7398 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3065 -0.2684 0.0991 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6287 -0.5681 0.2910 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0575 -0.0047 -0.0245 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6170 0.2877 -1.2523 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9599 0.5234 -1.4117 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7705 0.4661 -0.3129 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2724 0.1771 0.9498 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9196 -0.0543 1.0744 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1517 0.6930 -0.3874 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2667 2.2234 -1.5806 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3421 1.8218 1.0799 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5289 0.5267 0.9228 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0792 0.3045 1.9425 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2572 -1.3961 -1.6576 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2453 -1.2566 -0.1668 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4247 0.0270 -1.3805 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0513 1.9907 -1.4641 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7837 2.5199 -1.8056 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8993 -2.0089 1.3362 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9983 -2.2814 2.3428 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7018 -2.1276 1.8344 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9082 -4.0518 1.1689 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9551 0.3311 -2.1274 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3603 0.7463 -2.3698 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8933 0.1295 1.8097 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4984 -0.2818 2.0475 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4789 1.5874 -0.0030 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0895 3.0959 -1.1039 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 15 18 2 0 18 19 1 0 11 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 23 26 1 0 7 27 1 0 19 2 1 0 25 20 1 0 18 6 1 0 14 8 2 0 1 28 1 0 1 29 1 0 1 30 1 0 3 31 1 0 3 32 1 0 3 33 1 0 4 34 1 0 5 35 1 0 12 36 1 0 16 37 1 0 16 38 1 0 17 39 1 0 21 40 1 0 22 41 1 0 24 42 1 0 25 43 1 0 26 44 1 0 27 45 1 0 M END

Standard InCHIKey	YJZULEGLRQGVFQ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C21H18O6/c1-21(2)8-7-13-17(24)16-18(25)15(11-3-5-12(23)6-4-11)10-26-20(16)14(9-22)19(13)27-21/h3-8,10,22-24H,9H2,1-2H3
SMILES	CC1(C)C=Cc2c(c3c(=O)c(coc3c(CO)c2O1)c1ccc(cc1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	366.11	Volume:	366.56 ? Van der Waals volume.
Dense:	0.999	LogP:	2.2 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.257 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.131 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	23.0
TPSA:	100.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	4.0
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:	3.029	Fsp³:	0.19
MCE-18:	52.0 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.42	Fluc inhibitor:	0.513 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.683 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.664 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.136	Promiscuous compounds:	0.356

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.015	MDCK Permeability:	-4.751
Pgp-inhibitor:	0.112	Pgp-substrate:	0.024
PAMPA:	0.929 ? 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):	0.011
20% Bioavailability (F20%):	0.704	30% Bioavailability (F30%):	0.964
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.258	MRP1:	0.753
Plasma Protein Binding (PPB):	93.925%	Volume Distribution (VD):	-0.027
Fu:	5.082% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.986
OATP1B3 inhibitor:	0.574	BCRP inhibitor:	0.806
BSEP inhibitor:	0.984

ADMET: Metabolism

CYP1A2-inhibitor:	0.415	CYP1A2-substrate:	0.607
CYP2C19-inhibitor:	0.055	CYP2C19-substrate:	0.815
CYP2C9-inhibitor:	0.271	CYP2C9-substrate:	0.008
CYP2D6-inhibitor:	0.008	CYP2D6-substrate:	0.679
CYP3A4-inhibitor:	0.447	CYP3A4-substrate:	0.922
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	0.998
HLM stability:	0.376 ? 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):

4.906

Half-life (T1/2):

1.347

ADMET: Toxicity

hERG Blockers:	0.088	hERG Blockers (10um):	0.432
Human Hepatotoxicity (H-HT):	0.584	Drug-induced Liver Injury (DILI):	0.394
AMES Toxicity:	0.593	Rat Oral Acute Toxicity:	0.457
Maximum Recommended Daily Dose:	0.691	Skin Sensitization:	0.696
Carcinogencity:	0.851	Eye Corrosion:	0.002
Eye Irritation:	0.821	Respiratory Toxicity:	0.585
Drug-induced Neurotoxicity:	0.358	Ototoxicity:	0.413
Hematotoxicity:	0.172	Drug-induced Nephrotoxicity:	0.197
Genotoxicity:	0.814	RPMI-8226 Immunitoxicity:	0.074
A549 Cytotoxicity:	0.09	Hek293 Cytotoxicity:	0.526
BCF:	1.501 ? 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:	4.13 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.631 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.009 ? 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
NPO27387	Erythrina addisoniae	Species	Fabaceae	Eukaryota	Stems; Barks	n.a.	n.a.	PMID[12828487]
NPO27387	Erythrina addisoniae	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17517504]
NPO27387	Erythrina addisoniae	Species	Fabaceae	Eukaryota	Barks	n.a.	n.a.	PMID[18302333]
NPO27387	Erythrina addisoniae	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20934335]
NPO27387	Erythrina addisoniae	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23022281]
NPO27387	Erythrina addisoniae	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27387	Erythrina addisoniae	Species	Fabaceae	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

Activity Type	# Activity
IC50	2

Activity Type	# Activity
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT493	Individual protein	Neuraminidase	Influenza A virus	IC50	>	50.0	ug.mL-1	PMID[19715320]

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 NPC6511 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	22556
0.1-0.2	24202
0.2-0.3	2576
0.3-0.4	404
0.4-0.5	91
0.5-0.6	19
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
0.7612	Intermediate Similarity	NPC237635
0.7123	Intermediate Similarity	NPC470681
0.6806	Remote Similarity	NPC484044
0.6667	Remote Similarity	NPC170026
0.6667	Remote Similarity	NPC201731
0.6618	Remote Similarity	NPC97716
0.64	Remote Similarity	NPC200625
0.6143	Remote Similarity	NPC24673
0.5897	Remote Similarity	NPC188403
0.5844	Remote Similarity	NPC79469
0.5844	Remote Similarity	NPC282307
0.5821	Remote Similarity	NPC483565
0.5775	Remote Similarity	NPC600644
0.5714	Remote Similarity	NPC327269
0.5625	Remote Similarity	NPC91701
0.5584	Remote Similarity	NPC31627
0.5526	Remote Similarity	NPC84124
0.5373	Remote Similarity	NPC295384
0.5316	Remote Similarity	NPC484043
0.5205	Remote Similarity	NPC204985
0.519	Remote Similarity	NPC184755
0.5128	Remote Similarity	NPC184547
0.5128	Remote Similarity	NPC15435
0.5122	Remote Similarity	NPC476238
0.5063	Remote Similarity	NPC214236
0.5062	Remote Similarity	NPC233502
0.506	Remote Similarity	NPC28241

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC6511 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4215
0.1-0.2	4886
0.2-0.3	44
0.3-0.4	4
0.4-0.5	1
0.5-0.6	0
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
		NPD

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