NPASS Compound

Natural Product: NPC507662

Natural Product ID	NPC507662
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2S)-2-(3,5-dihydroxy-4-methoxyphenyl)-7-hydroxy-2,3-dihydrochromen-4-one
IUPAC Name	(2~{S})-2-(3,5-dihydroxy-4-methoxy-phenyl)-7-hydroxy-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 36 38 0 0 0 0 0 0 0 0999 V2000 5.9923 0.2476 -0.0457 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9899 0.5868 0.8590 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6373 0.3420 0.6651 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7908 1.2408 0.0479 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3129 2.4325 -0.3945 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4457 0.9926 -0.1427 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9123 -0.2026 0.2987 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5339 -0.5168 0.1162 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7707 -0.9988 -1.2971 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2057 -1.0324 -1.6090 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5711 -1.6762 -2.6346 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1531 -0.3384 -0.7483 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4988 -0.4972 -0.9829 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3784 0.1657 -0.1601 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9650 0.9787 0.8848 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8888 1.6344 1.6973 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6227 1.1289 1.1084 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7084 0.4667 0.2874 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3418 0.5741 0.4571 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7362 -1.1332 0.9259 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0770 -0.8464 1.0972 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8985 -1.7678 1.7195 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9751 0.4931 0.4522 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0548 -0.8400 -0.2658 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9773 0.7867 -0.9946 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8161 2.4559 -1.2646 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7781 1.7026 -0.6301 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8000 -1.3678 0.7864 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3675 -2.0308 -1.3554 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2570 -0.3942 -2.0528 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8319 -1.1380 -1.8067 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4403 0.0559 -0.3255 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8707 1.5636 1.4511 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2599 1.7589 1.9193 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2900 -2.0676 1.2643 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7810 -2.7595 1.4597 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 1 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 15 17 1 0 17 18 2 0 18 19 1 0 7 20 1 0 20 21 2 0 21 22 1 0 21 3 1 0 19 8 1 0 18 12 1 0 1 23 1 0 1 24 1 0 1 25 1 0 5 26 1 0 6 27 1 0 8 28 1 1 9 29 1 0 9 30 1 0 13 31 1 0 14 32 1 0 16 33 1 0 17 34 1 0 20 35 1 0 22 36 1 0 M END

Standard InCHIKey	FCBRIPJNIPRUCV-AWEZNQCLSA-N
Standard InCHI	InChI=1S/C16H14O6/c1-21-16-12(19)4-8(5-13(16)20)14-7-11(18)10-3-2-9(17)6-15(10)22-14/h2-6,14,17,19-20H,7H2,1H3/t14-/m0/s1
SMILES	COC1=C(O)C=C([C@@H]2CC(=O)C3=CC=C(O)C=C3O2)C=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	302.08	Volume:	293.909 ? Van der Waals volume.
Dense:	1.028	LogP:	2.236 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.418 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.949 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
TPSA:	96.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.789	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.04	Fsp³:	0.188
MCE-18:	57.789 ? 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:	0
Colloidal aggregators:	0.54	Fluc inhibitor:	0.831 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.288 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.435 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.383	Promiscuous compounds:	0.075

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.006	MDCK Permeability:	-4.79
Pgp-inhibitor:	0.085	Pgp-substrate:	0.02
PAMPA:	0.346 ? 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):	0.002
20% Bioavailability (F20%):	0.186	30% Bioavailability (F30%):	0.695
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.008	MRP1:	0.809
Plasma Protein Binding (PPB):	93.481%	Volume Distribution (VD):	-0.534
Fu:	6.874% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.94
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.826
BSEP inhibitor:	0.192

ADMET: Metabolism

CYP1A2-inhibitor:	0.942	CYP1A2-substrate:	0.894
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.997
CYP2C9-inhibitor:	0.01	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.784
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.541 ? 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):

4.776

Half-life (T1/2):

1.665

ADMET: Toxicity

hERG Blockers:	0.133	hERG Blockers (10um):	0.514
Human Hepatotoxicity (H-HT):	0.729	Drug-induced Liver Injury (DILI):	0.849
AMES Toxicity:	0.676	Rat Oral Acute Toxicity:	0.709
Maximum Recommended Daily Dose:	0.794	Skin Sensitization:	0.883
Carcinogencity:	0.636	Eye Corrosion:	0.167
Eye Irritation:	0.993	Respiratory Toxicity:	0.924
Drug-induced Neurotoxicity:	0.748	Ototoxicity:	0.285
Hematotoxicity:	0.198	Drug-induced Nephrotoxicity:	0.538
Genotoxicity:	0.966	RPMI-8226 Immunitoxicity:	0.117
A549 Cytotoxicity:	0.719	Hek293 Cytotoxicity:	0.632
BCF:	0.73 ? 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:	3.191 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.479 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.886 ? 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
NPO51588	Dioclea reflexa	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 NPC507662 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	24282
0.1-0.2	20339
0.2-0.3	4462
0.3-0.4	601
0.4-0.5	121
0.5-0.6	30
0.6-0.7	8
0.7-0.8	1
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
0.7708	Intermediate Similarity	NPC264083
0.7447	Intermediate Similarity	NPC329225
0.7447	Intermediate Similarity	NPC147686
0.72	Intermediate Similarity	NPC1612
0.72	Intermediate Similarity	NPC183959
0.7143	Intermediate Similarity	NPC476480
0.7143	Intermediate Similarity	NPC84585
0.6346	Remote Similarity	NPC472460
0.6333	Remote Similarity	NPC474033
0.6271	Remote Similarity	NPC68104
0.6182	Remote Similarity	NPC609065
0.6111	Remote Similarity	NPC480993
0.6034	Remote Similarity	NPC143896
0.6032	Remote Similarity	NPC474034
0.6	Remote Similarity	NPC210084
0.5873	Remote Similarity	NPC291508
0.5849	Remote Similarity	NPC225153
0.5849	Remote Similarity	NPC479876
0.5833	Remote Similarity	NPC221432
0.5833	Remote Similarity	NPC257097
0.5714	Remote Similarity	NPC486095
0.5714	Remote Similarity	NPC606248
0.5556	Remote Similarity	NPC188243
0.5556	Remote Similarity	NPC110228
0.5536	Remote Similarity	NPC99597
0.5517	Remote Similarity	NPC302950
0.5469	Remote Similarity	NPC23728
0.5439	Remote Similarity	NPC480995
0.5439	Remote Similarity	NPC477503
0.537	Remote Similarity	NPC265871
0.537	Remote Similarity	NPC205093
0.5294	Remote Similarity	NPC170475
0.5286	Remote Similarity	NPC209040
0.5263	Remote Similarity	NPC274784
0.5263	Remote Similarity	NPC20709
0.5263	Remote Similarity	NPC329203
0.5263	Remote Similarity	NPC222342
0.5263	Remote Similarity	NPC610021
0.5179	Remote Similarity	NPC32441
0.5179	Remote Similarity	NPC79943
0.5172	Remote Similarity	NPC470356
0.5172	Remote Similarity	NPC480992
0.5172	Remote Similarity	NPC475267
0.5085	Remote Similarity	NPC18727
0.5082	Remote Similarity	NPC236637

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC507662 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3792
0.1-0.2	5189
0.2-0.3	149
0.3-0.4	15
0.4-0.5	2
0.5-0.6	2
0.6-0.7	0
0.7-0.8	1
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
0.7447	Intermediate Similarity	NPD1549	Phase 2
0.5517	Remote Similarity	NPD1934	Phase 0
0.5179	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