NPASS Compound

Natural Product: NPC500761

Natural Product ID	NPC500761
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	schliebenone C
IUPAC Name	5,7-dihydroxy-3-[3-hydroxy-5-(3-hydroxy-3-methyl-but-1-enyl)-4-methoxy-phenyl]chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0002586] O-methylated isoflavonoids [CHEMONTID:0002606] 4'-O-methylated isoflavonoids [CHEMONTID:0003651] 3'-hydroxy,4'-methoxyisoflavonoids

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 48 50 0 0 0 0 0 0 0 0999 V2000 -2.5160 -1.6956 -4.0780 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2302 -0.4993 -3.4246 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1970 -0.2922 -2.5304 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0166 0.1307 -3.0130 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2223 0.3536 -4.3857 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0427 0.3355 -2.1164 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8976 0.1331 -0.7621 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9602 0.3432 0.1941 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1966 -0.5843 1.1793 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1735 -0.3444 2.0207 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9450 0.7005 2.0067 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9574 0.8479 2.9589 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7763 1.9559 2.9451 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7967 2.1221 3.8908 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5492 2.8951 1.9605 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5534 2.7614 1.0148 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3247 3.7095 0.0215 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7313 1.6468 1.0306 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7261 1.4804 0.1010 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5307 2.3528 -0.7974 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3380 -0.2933 -0.3059 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3943 -0.5121 -1.1611 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6930 -0.9567 -0.7095 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9784 -1.1915 0.5439 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3250 -1.6500 0.9933 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2482 -1.6582 -0.2031 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8131 -0.7455 2.0869 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2496 -2.9604 1.4639 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5174 -1.5945 -5.1973 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8361 -2.5242 -3.8212 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5435 -2.0118 -3.7675 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2833 1.1045 -4.8319 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0253 0.6713 -2.4511 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5919 -1.5022 1.2686 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1264 0.1048 3.7266 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3560 1.3267 4.1996 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1759 3.7788 1.9216 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3054 4.7044 0.2857 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4530 -0.4543 0.7715 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4722 -1.1044 -1.4393 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2531 -1.0679 1.3395 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2921 -1.9351 0.0935 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3053 -0.6702 -0.6620 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9217 -2.4349 -0.9110 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8063 -0.3396 1.7731 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1186 0.1097 2.1705 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8959 -1.2938 3.0623 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2999 -3.2520 1.5437 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 4 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 13 15 2 0 15 16 1 0 16 17 1 0 16 18 2 0 18 19 1 0 19 20 2 0 7 21 1 0 21 22 2 0 22 23 1 0 23 24 2 3 24 25 1 0 25 26 1 0 25 27 1 0 25 28 1 0 22 3 1 0 19 8 1 0 18 11 1 0 1 29 1 0 1 30 1 0 1 31 1 0 5 32 1 0 6 33 1 0 9 34 1 0 12 35 1 0 14 36 1 0 15 37 1 0 17 38 1 0 21 39 1 0 23 40 1 0 24 41 1 0 26 42 1 0 26 43 1 0 26 44 1 0 27 45 1 0 27 46 1 0 27 47 1 0 28 48 1 0 M END

Standard InCHIKey	HZMQJHMUAPRPTR-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C21H20O7/c1-21(2,26)5-4-11-6-12(7-16(24)20(11)27-3)14-10-28-17-9-13(22)8-15(23)18(17)19(14)25/h4-10,22-24,26H,1-3H3
SMILES	COC1=C(O)C=C(C2=COC3=CC(O)=CC(O)=C3C2=O)C=C1C=CC(C)(C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	384.12	Volume:	383.906 ? Van der Waals volume.
Dense:	1.001	LogP:	2.206 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.1 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.846 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	19.0
TPSA:	120.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.544	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.036	Fsp³:	0.19
MCE-18:	22.0 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.453	Fluc inhibitor:	0.578 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.921 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.656 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.319	Promiscuous compounds:	0.556

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.307	MDCK Permeability:	-4.896
Pgp-inhibitor:	0.003	Pgp-substrate:	0.605
PAMPA:	0.389 ? 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%):	0.014	30% Bioavailability (F30%):	0.143
50% Bioavailability (F50%):	0.958

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.102	MRP1:	0.513
Plasma Protein Binding (PPB):	91.887%	Volume Distribution (VD):	-0.483
Fu:	4.881% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.576
OATP1B3 inhibitor:	0.893	BCRP inhibitor:	0.975
BSEP inhibitor:	0.145

ADMET: Metabolism

CYP1A2-inhibitor:	0.999	CYP1A2-substrate:	0.475
CYP2C19-inhibitor:	0.208	CYP2C19-substrate:	0.02
CYP2C9-inhibitor:	0.84	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.968	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	0.207	CYP3A4-substrate:	0.254
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	1.0
HLM stability:	0.134 ? 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):

2.846

Half-life (T1/2):

1.433

ADMET: Toxicity

hERG Blockers:	0.103	hERG Blockers (10um):	0.463
Human Hepatotoxicity (H-HT):	0.538	Drug-induced Liver Injury (DILI):	0.609
AMES Toxicity:	0.683	Rat Oral Acute Toxicity:	0.595
Maximum Recommended Daily Dose:	0.901	Skin Sensitization:	0.567
Carcinogencity:	0.728	Eye Corrosion:	0.001
Eye Irritation:	0.936	Respiratory Toxicity:	0.835
Drug-induced Neurotoxicity:	0.067	Ototoxicity:	0.301
Hematotoxicity:	0.091	Drug-induced Nephrotoxicity:	0.222
Genotoxicity:	0.985	RPMI-8226 Immunitoxicity:	0.131
A549 Cytotoxicity:	0.448	Hek293 Cytotoxicity:	0.723
BCF:	0.9 ? 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:	3.537 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.784 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.102 ? 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
NPO40124	Erythrina schliebenii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28112509]
NPO40124	Erythrina schliebenii	Species	Fabaceae	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 NPC500761 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	22356
0.1-0.2	24122
0.2-0.3	2750
0.3-0.4	507
0.4-0.5	80
0.5-0.6	31
0.6-0.7	8
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
0.8308	Intermediate Similarity	NPC482075
0.75	Intermediate Similarity	NPC74178
0.6957	Remote Similarity	NPC128774
0.6515	Remote Similarity	NPC194653
0.6515	Remote Similarity	NPC481044
0.6216	Remote Similarity	NPC52889
0.6176	Remote Similarity	NPC254702
0.6154	Remote Similarity	NPC78341
0.6061	Remote Similarity	NPC294409
0.6061	Remote Similarity	NPC490701
0.5882	Remote Similarity	NPC200316
0.5867	Remote Similarity	NPC107838
0.5735	Remote Similarity	NPC19980
0.5735	Remote Similarity	NPC239363
0.5733	Remote Similarity	NPC474052
0.5714	Remote Similarity	NPC483637
0.5714	Remote Similarity	NPC193792
0.5714	Remote Similarity	NPC45291
0.5692	Remote Similarity	NPC38065
0.5676	Remote Similarity	NPC233918
0.5676	Remote Similarity	NPC268059
0.5652	Remote Similarity	NPC309154
0.5625	Remote Similarity	NPC39426
0.5584	Remote Similarity	NPC108859
0.5493	Remote Similarity	NPC142876
0.5493	Remote Similarity	NPC264550
0.5479	Remote Similarity	NPC238279
0.5417	Remote Similarity	NPC104728
0.5395	Remote Similarity	NPC479305
0.5385	Remote Similarity	NPC608554
0.5366	Remote Similarity	NPC278968
0.5352	Remote Similarity	NPC279668
0.5352	Remote Similarity	NPC278323
0.5342	Remote Similarity	NPC167595
0.5263	Remote Similarity	NPC475705
0.5244	Remote Similarity	NPC303174
0.52	Remote Similarity	NPC213659
0.52	Remote Similarity	NPC326109
0.5125	Remote Similarity	NPC474960
0.5063	Remote Similarity	NPC231763
0.5063	Remote Similarity	NPC303197

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC500761 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4521
0.1-0.2	4584
0.2-0.3	40
0.3-0.4	4
0.4-0.5	0
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
0.5625	Remote Similarity	NPD1510	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