NPASS Compound

Natural Product: NPC566061

Natural Product ID	NPC566061
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ent-Epifisetinidol
IUPAC Name	(2~{S},3~{S})-2-(3,4-dihydroxyphenyl)chromane-3,7-diol
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 34 36 0 0 0 0 0 0 0 0999 V2000 -5.0286 2.1715 1.2369 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2032 1.1618 0.7607 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6446 -0.1005 0.4524 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7709 -1.0777 -0.0232 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4346 -0.7815 -0.1910 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5527 -1.8506 -0.6962 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0943 -1.5249 -0.5915 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3669 -1.8795 0.6748 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2102 -0.0687 -0.8088 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6119 0.2824 -0.4821 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9898 1.6137 -0.3472 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2784 1.9962 -0.0511 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2365 1.0068 0.1189 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5415 1.4231 0.4201 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9204 -0.3221 -0.0025 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9085 -1.2958 0.1747 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6104 -0.6485 -0.3012 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6568 0.7643 -0.0547 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9980 0.4722 0.1155 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8526 1.4559 0.5894 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7011 2.7319 2.0321 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6804 -0.3321 0.5819 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2059 -2.0395 -0.2388 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8372 -2.1090 -1.7405 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7499 -2.7570 -0.0863 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4508 -2.1391 -1.3272 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4793 -2.8782 0.7091 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0541 0.2108 -1.8723 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2068 2.3478 -0.4891 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5252 3.0470 0.0442 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0548 2.0627 -0.1576 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9937 -1.6663 1.1331 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4031 -1.7010 -0.3924 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4316 2.4241 0.8098 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 1 0 7 8 1 0 7 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 13 15 1 0 15 16 1 0 15 17 2 0 9 18 1 0 18 19 1 0 19 20 2 0 20 2 1 0 19 5 1 0 17 10 1 0 1 21 1 0 3 22 1 0 4 23 1 0 6 24 1 0 6 25 1 0 7 26 1 6 8 27 1 0 9 28 1 6 11 29 1 0 12 30 1 0 14 31 1 0 16 32 1 0 17 33 1 0 20 34 1 0 M END

Standard InCHIKey	VFZYLYJWCROVLO-ZFWWWQNUSA-N
Standard InCHI	InChI=1S/C15H14O5/c16-10-3-1-8-5-13(19)15(20-14(8)7-10)9-2-4-11(17)12(18)6-9/h1-4,6-7,13,15-19H,5H2/t13-,15-/m0/s1
SMILES	OC1=CC=C2C[C@H](O)[C@H](C3=CC=C(O)C(O)=C3)OC2=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	274.08	Volume:	270.459 ? Van der Waals volume.
Dense:	1.013	LogP:	1.156 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.419 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.03 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	17.0
TPSA:	90.15 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.596	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.137	Fsp³:	0.2
MCE-18:	56.667 ? 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:	1
Colloidal aggregators:	0.654	Fluc inhibitor:	0.618 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.041 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.069 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.477	Promiscuous compounds:	0.335

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.89	MDCK Permeability:	-4.862
Pgp-inhibitor:	0.002	Pgp-substrate:	0.085
PAMPA:	0.263 ? 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%):	0.896	30% Bioavailability (F30%):	0.975
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.61
Plasma Protein Binding (PPB):	83.45%	Volume Distribution (VD):	0.029
Fu:	24.66% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.992
OATP1B3 inhibitor:	0.984	BCRP inhibitor:	0.028
BSEP inhibitor:	0.378

ADMET: Metabolism

CYP1A2-inhibitor:	0.041	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.006	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.036	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.118	CYP2D6-substrate:	0.065
CYP3A4-inhibitor:	0.058	CYP3A4-substrate:	0.01
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.1
HLM stability:	0.009 ? 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):

16.328

Half-life (T1/2):

2.53

ADMET: Toxicity

hERG Blockers:	0.141	hERG Blockers (10um):	0.71
Human Hepatotoxicity (H-HT):	0.711	Drug-induced Liver Injury (DILI):	0.104
AMES Toxicity:	0.6	Rat Oral Acute Toxicity:	0.38
Maximum Recommended Daily Dose:	0.673	Skin Sensitization:	0.931
Carcinogencity:	0.295	Eye Corrosion:	0.075
Eye Irritation:	0.994	Respiratory Toxicity:	0.441
Drug-induced Neurotoxicity:	0.105	Ototoxicity:	0.77
Hematotoxicity:	0.054	Drug-induced Nephrotoxicity:	0.1
Genotoxicity:	0.856	RPMI-8226 Immunitoxicity:	0.015
A549 Cytotoxicity:	0.407	Hek293 Cytotoxicity:	0.482
BCF:	1.108 ? 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:	3.268 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.272 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.99 ? 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
NPO12013	Colophospermum mopane	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26444248]
NPO12013	Colophospermum mopane	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12013	Colophospermum mopane	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12013	Colophospermum mopane	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

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 NPC566061 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	23518
0.1-0.2	21182
0.2-0.3	4433
0.3-0.4	537
0.4-0.5	126
0.5-0.6	49
0.6-0.7	9
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	NPC601844
0.6875	Remote Similarity	NPC261619
0.6875	Remote Similarity	NPC61477
0.6875	Remote Similarity	NPC78770
0.6875	Remote Similarity	NPC219876
0.6875	Remote Similarity	NPC126029
0.6875	Remote Similarity	NPC15658
0.6604	Remote Similarity	NPC482704
0.64	Remote Similarity	NPC246328
0.64	Remote Similarity	NPC27532
0.5932	Remote Similarity	NPC82917
0.58	Remote Similarity	NPC207179
0.58	Remote Similarity	NPC167571
0.58	Remote Similarity	NPC278552
0.5645	Remote Similarity	NPC313116
0.5645	Remote Similarity	NPC603340
0.5625	Remote Similarity	NPC93398
0.5625	Remote Similarity	NPC258979
0.5625	Remote Similarity	NPC8283
0.5556	Remote Similarity	NPC36835
0.5556	Remote Similarity	NPC246162
0.5556	Remote Similarity	NPC9743
0.5556	Remote Similarity	NPC260491
0.5556	Remote Similarity	NPC61506
0.5556	Remote Similarity	NPC240476
0.5469	Remote Similarity	NPC70409
0.5469	Remote Similarity	NPC204770
0.5469	Remote Similarity	NPC600551
0.5469	Remote Similarity	NPC601980
0.5469	Remote Similarity	NPC602065
0.5469	Remote Similarity	NPC611024
0.541	Remote Similarity	NPC58190
0.541	Remote Similarity	NPC108811
0.541	Remote Similarity	NPC170103
0.541	Remote Similarity	NPC236202
0.541	Remote Similarity	NPC262911
0.541	Remote Similarity	NPC202742
0.5357	Remote Similarity	NPC178054
0.5323	Remote Similarity	NPC246202
0.5323	Remote Similarity	NPC224161
0.5323	Remote Similarity	NPC46335
0.5323	Remote Similarity	NPC294558
0.5323	Remote Similarity	NPC18185
0.5323	Remote Similarity	NPC263940
0.5323	Remote Similarity	NPC279406
0.5323	Remote Similarity	NPC486519
0.5303	Remote Similarity	NPC600630
0.5303	Remote Similarity	NPC607896
0.5303	Remote Similarity	NPC611369
0.5192	Remote Similarity	NPC268266
0.5192	Remote Similarity	NPC42760
0.5192	Remote Similarity	NPC220825
0.5192	Remote Similarity	NPC268342
0.5185	Remote Similarity	NPC325028
0.5185	Remote Similarity	NPC256346
0.5185	Remote Similarity	NPC103799
0.5185	Remote Similarity	NPC606550
0.5172	Remote Similarity	NPC150670
0.5156	Remote Similarity	NPC28440

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC566061 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4531
0.1-0.2	4415
0.2-0.3	189
0.3-0.4	11
0.4-0.5	2
0.5-0.6	0
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
0.6875	Remote Similarity	NPD1612	Clinical (unspecified phase)
0.6875	Remote Similarity	NPD1613	Phase 4

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