NPASS Compound

Natural Product: NPC546525

Natural Product ID	NPC546525
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{S})-7,8-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one
IUPAC Name	(2~{S})-7,8-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 32 34 0 0 0 0 0 0 0 0999 V2000 1.7004 -3.2556 0.7124 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2821 -2.1385 0.3221 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1753 -1.9684 0.0966 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4956 -0.6751 -0.5930 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8789 -0.2279 -0.3899 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8693 -0.9943 0.1883 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1717 -0.5166 0.3577 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4639 0.7605 -0.0697 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7507 1.2793 0.0791 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5102 1.5451 -0.6450 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2384 1.0413 -0.7955 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4100 0.3686 -0.2002 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7676 0.2102 -0.1546 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2519 -1.0758 0.1137 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6126 -1.2964 0.1721 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4848 -0.2492 -0.0341 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0128 1.0331 -0.3015 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9664 2.0209 -0.4947 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6544 1.2478 -0.3587 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2140 2.5267 -0.6251 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5097 -2.8377 -0.5065 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6837 -2.0649 1.0877 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3293 -0.8077 -1.6847 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6377 -1.9883 0.5194 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9418 -1.1264 0.8128 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8585 2.2104 0.4781 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7830 2.5518 -0.9701 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4975 1.6824 -1.2550 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9804 -2.3038 0.3821 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5469 -0.4237 0.0120 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2270 2.3779 -1.4068 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6843 3.0944 0.0159 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 2 0 16 17 1 0 17 18 1 0 17 19 2 0 19 20 1 0 14 2 1 0 11 5 1 0 19 13 1 0 3 21 1 0 3 22 1 0 4 23 1 6 6 24 1 0 7 25 1 0 9 26 1 0 10 27 1 0 11 28 1 0 15 29 1 0 16 30 1 0 18 31 1 0 20 32 1 0 M END

Standard InCHIKey	IXQZKAVXZDCYDY-ZDUSSCGKSA-N
Standard InCHI	InChI=1S/C15H12O5/c16-9-3-1-8(2-4-9)13-7-12(18)10-5-6-11(17)14(19)15(10)20-13/h1-6,13,16-17,19H,7H2/t13-/m0/s1
SMILES	O=C1C[C@@H](C2=CC=C(O)C=C2)OC2=C1C=CC(O)=C2O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	272.07	Volume:	267.823 ? Van der Waals volume.
Dense:	1.016	LogP:	2.226 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.365 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.883 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	86.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.694	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.887	Fsp³:	0.133
MCE-18:	55.0 ? 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:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.71	Fluc inhibitor:	0.591 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.197 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.237 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.622	Promiscuous compounds:	0.103

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.188	MDCK Permeability:	-4.782
Pgp-inhibitor:	0.521	Pgp-substrate:	0.091
PAMPA:	0.653 ? 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%):	0.007	30% Bioavailability (F30%):	0.927
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.934
Plasma Protein Binding (PPB):	91.138%	Volume Distribution (VD):	-0.341
Fu:	10.571% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.553
OATP1B3 inhibitor:	0.977	BCRP inhibitor:	0.999
BSEP inhibitor:	0.293

ADMET: Metabolism

CYP1A2-inhibitor:	0.008	CYP1A2-substrate:	0.368
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.972
CYP2C9-inhibitor:	0.015	CYP2C9-substrate:	0.004
CYP2D6-inhibitor:	0.244	CYP2D6-substrate:	0.883
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.82
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.55
HLM stability:	0.97 ? 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):

7.779

Half-life (T1/2):

1.668

ADMET: Toxicity

hERG Blockers:	0.126	hERG Blockers (10um):	0.559
Human Hepatotoxicity (H-HT):	0.654	Drug-induced Liver Injury (DILI):	0.281
AMES Toxicity:	0.677	Rat Oral Acute Toxicity:	0.386
Maximum Recommended Daily Dose:	0.559	Skin Sensitization:	0.918
Carcinogencity:	0.573	Eye Corrosion:	0.064
Eye Irritation:	0.994	Respiratory Toxicity:	0.08
Drug-induced Neurotoxicity:	0.59	Ototoxicity:	0.473
Hematotoxicity:	0.092	Drug-induced Nephrotoxicity:	0.261
Genotoxicity:	0.903	RPMI-8226 Immunitoxicity:	0.037
A549 Cytotoxicity:	0.481	Hek293 Cytotoxicity:	0.46
BCF:	1.12 ? 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:	3.711 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.566 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.184 ? 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
NPO42311	Acacia spp.	Genus	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 NPC546525 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	23598
0.1-0.2	21991
0.2-0.3	3720
0.3-0.4	401
0.4-0.5	111
0.5-0.6	30
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	Natural Product ID
0.7955	Intermediate Similarity	NPC103991
0.6739	Remote Similarity	NPC329225
0.6739	Remote Similarity	NPC147686
0.5882	Remote Similarity	NPC1612
0.5882	Remote Similarity	NPC183959
0.58	Remote Similarity	NPC476480
0.58	Remote Similarity	NPC84585
0.566	Remote Similarity	NPC210084
0.5577	Remote Similarity	NPC167624
0.5577	Remote Similarity	NPC166482
0.549	Remote Similarity	NPC225153
0.549	Remote Similarity	NPC479876
0.5472	Remote Similarity	NPC324386
0.5439	Remote Similarity	NPC164980
0.5385	Remote Similarity	NPC32441
0.5385	Remote Similarity	NPC264083
0.5385	Remote Similarity	NPC79943
0.5385	Remote Similarity	NPC603284
0.5185	Remote Similarity	NPC300668
0.5185	Remote Similarity	NPC329203
0.5185	Remote Similarity	NPC222342
0.5185	Remote Similarity	NPC610021
0.5172	Remote Similarity	NPC169591
0.5172	Remote Similarity	NPC298223
0.5172	Remote Similarity	NPC604412
0.5091	Remote Similarity	NPC485881
0.5091	Remote Similarity	NPC469764
0.5091	Remote Similarity	NPC475267
0.5091	Remote Similarity	NPC606248
0.5085	Remote Similarity	NPC39329
0.5085	Remote Similarity	NPC472580
0.5085	Remote Similarity	NPC51032
0.5079	Remote Similarity	NPC28589

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC546525 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3331
0.1-0.2	5652
0.2-0.3	156
0.3-0.4	6
0.4-0.5	3
0.5-0.6	1
0.6-0.7	1
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
0.6739	Remote Similarity	NPD1549	Phase 2
0.5385	Remote Similarity	NPD1552	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