NPASS Compound

Natural Product: NPC584661

Natural Product ID	NPC584661
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Milimorin
IUPAC Name	3,5,7-trihydroxy-2-(2-hydroxy-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]

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 35 37 0 0 0 0 0 0 0 0999 V2000 6.2706 -0.1464 0.7622 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1642 -0.7983 1.3087 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8503 -0.4837 0.9868 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8156 -1.1750 1.5707 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5207 -0.8395 1.2319 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1985 0.1647 0.3276 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2185 0.3443 0.0577 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8015 1.4459 -0.5184 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0855 2.5444 -0.9174 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1883 1.5168 -0.7316 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7051 2.5333 -1.2623 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9825 0.4676 -0.3571 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3464 0.4331 -0.5192 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9546 1.5250 -1.0962 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1179 -0.6426 -0.1294 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4956 -1.7195 0.4426 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2577 -2.8084 0.8397 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1355 -1.7071 0.6143 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3485 -0.6111 0.2172 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0665 -0.6278 0.3914 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2159 0.8446 -0.2490 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0371 1.8625 -1.1723 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5332 0.5032 0.0968 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1915 -0.5248 1.2428 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3925 -0.3411 -0.3371 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2028 0.9594 0.8516 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0240 -1.9721 2.2888 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7233 -1.4104 1.7174 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3473 3.0998 -1.7222 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7943 1.6750 -2.1004 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1800 -0.6367 -0.2706 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0473 -3.7175 0.4018 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6619 -2.5630 1.0662 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2413 1.7612 -2.1570 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3537 1.0442 -0.3598 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 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 8 10 1 0 10 11 2 0 10 12 1 0 12 13 2 0 13 14 1 0 13 15 1 0 15 16 2 0 16 17 1 0 16 18 1 0 18 19 2 0 19 20 1 0 6 21 1 0 21 22 1 0 21 23 2 0 23 3 1 0 20 7 1 0 19 12 1 0 1 24 1 0 1 25 1 0 1 26 1 0 4 27 1 0 5 28 1 0 9 29 1 0 14 30 1 0 15 31 1 0 17 32 1 0 18 33 1 0 22 34 1 0 23 35 1 0 M END

Standard InCHIKey	FIIRWIFMLHSBSP-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H12O7/c1-22-8-2-3-9(10(18)6-8)16-15(21)14(20)13-11(19)4-7(17)5-12(13)23-16/h2-6,17-19,21H,1H3
SMILES	COC1=CC=C(C2=C(O)C(=O)C3=C(O)C=C(O)C=C3O2)C(O)=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	316.06	Volume:	300.063 ? Van der Waals volume.
Dense:	1.053	LogP:	2.004 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.136 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.201 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
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:	0.572	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.51	Fsp³:	0.062
MCE-18:	19.0 ? 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:	0.788	Fluc inhibitor:	0.741 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.903 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.486 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.549	Promiscuous compounds:	0.919

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.53	MDCK Permeability:	-4.877
Pgp-inhibitor:	0.541	Pgp-substrate:	0.261
PAMPA:	0.221 ? 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):	0.137
20% Bioavailability (F20%):	0.089	30% Bioavailability (F30%):	0.814
50% Bioavailability (F50%):	0.98

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.831
Plasma Protein Binding (PPB):	97.593%	Volume Distribution (VD):	-0.527
Fu:	1.591% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.899
OATP1B3 inhibitor:	0.994	BCRP inhibitor:	0.989
BSEP inhibitor:	0.738

ADMET: Metabolism

CYP1A2-inhibitor:	0.953	CYP1A2-substrate:	0.116
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.562
CYP2C9-inhibitor:	0.958	CYP2C9-substrate:	0.086
CYP2D6-inhibitor:	0.999	CYP2D6-substrate:	0.933
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.997 ? 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):

5.32

Half-life (T1/2):

1.397

ADMET: Toxicity

hERG Blockers:	0.061	hERG Blockers (10um):	0.445
Human Hepatotoxicity (H-HT):	0.388	Drug-induced Liver Injury (DILI):	0.777
AMES Toxicity:	0.643	Rat Oral Acute Toxicity:	0.44
Maximum Recommended Daily Dose:	0.739	Skin Sensitization:	0.464
Carcinogencity:	0.73	Eye Corrosion:	0.358
Eye Irritation:	0.996	Respiratory Toxicity:	0.847
Drug-induced Neurotoxicity:	0.034	Ototoxicity:	0.093
Hematotoxicity:	0.088	Drug-induced Nephrotoxicity:	0.06
Genotoxicity:	0.897	RPMI-8226 Immunitoxicity:	0.086
A549 Cytotoxicity:	0.32	Hek293 Cytotoxicity:	0.665
BCF:	1.111 ? 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:	3.789 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.419 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.909 ? 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
NPO52976	Euphorbia mili	Genus	Euphorbiaceae	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 NPC584661 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	28257
0.1-0.2	17990
0.2-0.3	2634
0.3-0.4	766
0.4-0.5	163
0.5-0.6	34
0.6-0.7	13
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
0.7736	Intermediate Similarity	NPC241838
0.6981	Remote Similarity	NPC216361
0.6852	Remote Similarity	NPC256042
0.6842	Remote Similarity	NPC54394
0.6842	Remote Similarity	NPC159103
0.6607	Remote Similarity	NPC219330
0.6491	Remote Similarity	NPC50403
0.6491	Remote Similarity	NPC28274
0.6333	Remote Similarity	NPC125062
0.6167	Remote Similarity	NPC609179
0.6071	Remote Similarity	NPC179271
0.6066	Remote Similarity	NPC133953
0.6	Remote Similarity	NPC116775
0.6	Remote Similarity	NPC187432
0.5932	Remote Similarity	NPC59951
0.5932	Remote Similarity	NPC231772
0.5893	Remote Similarity	NPC20791
0.5893	Remote Similarity	NPC601197
0.5806	Remote Similarity	NPC279668
0.5667	Remote Similarity	NPC143799
0.5614	Remote Similarity	NPC169749
0.55	Remote Similarity	NPC44079
0.55	Remote Similarity	NPC152042
0.5484	Remote Similarity	NPC200740
0.5484	Remote Similarity	NPC166753
0.541	Remote Similarity	NPC201451
0.541	Remote Similarity	NPC87125
0.5397	Remote Similarity	NPC12200
0.5397	Remote Similarity	NPC603596
0.5352	Remote Similarity	NPC171821
0.5246	Remote Similarity	NPC184536
0.5246	Remote Similarity	NPC103342
0.5246	Remote Similarity	NPC608872
0.5238	Remote Similarity	NPC82325
0.5161	Remote Similarity	NPC286342
0.5161	Remote Similarity	NPC62536
0.5161	Remote Similarity	NPC281207
0.5161	Remote Similarity	NPC483773
0.5161	Remote Similarity	NPC605755
0.5161	Remote Similarity	NPC610359
0.5156	Remote Similarity	NPC52005
0.5156	Remote Similarity	NPC608664
0.5079	Remote Similarity	NPC49824
0.5079	Remote Similarity	NPC86485
0.5079	Remote Similarity	NPC294409
0.5079	Remote Similarity	NPC490701
0.5077	Remote Similarity	NPC252933
0.5077	Remote Similarity	NPC278323

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC584661 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5158
0.1-0.2	3914
0.2-0.3	72
0.3-0.4	3
0.4-0.5	2
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
0.5893	Remote Similarity	NPD1512	Phase 3

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