NPASS Compound

Natural Product: NPC235115

Natural Product ID	NPC235115
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(+)-6-Hydroxymellein
IUPAC Name	(3S)-6,8-dihydroxy-3-methyl-3,4-dihydroisochromen-1-one
Synonyms	(+)-6-Hydroxymellein
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL446047
PubChem CID	14353462
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002279] Benzene and substituted derivatives [CHEMONTID:0000176] Benzoic acids and derivatives [CHEMONTID:0001248] Hydroxybenzoic acid derivatives

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 24 25 0 0 0 0 0 0 0 0999 V2000 -3.4995 -0.6301 0.1577 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1066 -0.0553 0.2061 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.9599 0.9018 -0.8274 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7294 1.5399 -0.9093 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5902 2.7129 -1.3626 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4230 0.7793 -0.4382 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2841 -0.4994 0.0577 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0567 -1.1383 0.1243 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4062 -1.2000 0.5003 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6754 -0.6587 0.4630 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7963 0.6223 -0.0365 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6919 1.3224 -0.4763 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7905 2.6179 -0.9847 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7932 -1.3675 0.9082 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1882 0.1679 -0.1699 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8177 -0.9354 1.1735 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5417 -1.4505 -0.5806 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0157 0.4868 1.1695 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1003 -1.7258 1.0580 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2333 -1.7910 -0.7437 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3106 -2.1942 0.8877 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7910 1.0714 -0.0758 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5998 3.3624 -0.3223 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2771 -1.9387 0.2211 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 4 6 1 0 6 7 2 0 7 8 1 0 7 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 10 14 1 0 8 2 1 0 12 6 1 0 1 15 1 0 1 16 1 0 1 17 1 0 2 18 1 1 8 19 1 0 8 20 1 0 9 21 1 0 11 22 1 0 13 23 1 0 14 24 1 0 M END

Standard InCHIKey	DHLPMLVSBRRUGA-YFKPBYRVSA-N
Standard InCHI	InChI=1S/C10H10O4/c1-5-2-6-3-7(11)4-8(12)9(6)10(13)14-5/h3-5,11-12H,2H2,1H3/t5-/m0/s1
SMILES	C[C@@H]1OC(=O)c2c(C1)cc(cc2O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	194.06	Volume:	189.018 ? Van der Waals volume.
Dense:	1.027	LogP:	1.501 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.747 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.731 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	12.0
TPSA:	66.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.609	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.934	Fsp³:	0.3
MCE-18:	39.692 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.294	Fluc inhibitor:	0.137 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.273 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.287 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.734	Promiscuous compounds:	0.784

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.002	MDCK Permeability:	-4.741
Pgp-inhibitor:	0.487	Pgp-substrate:	0.095
PAMPA:	0.279 ? 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):	0.031
20% Bioavailability (F20%):	0.306	30% Bioavailability (F30%):	0.934
50% Bioavailability (F50%):	0.98

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.205	MRP1:	0.862
Plasma Protein Binding (PPB):	86.822%	Volume Distribution (VD):	-0.108
Fu:	11.483% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.989
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.812
BSEP inhibitor:	0.893

ADMET: Metabolism

CYP1A2-inhibitor:	0.831	CYP1A2-substrate:	0.479
CYP2C19-inhibitor:	0.156	CYP2C19-substrate:	0.161
CYP2C9-inhibitor:	0.72	CYP2C9-substrate:	0.912
CYP2D6-inhibitor:	0.068	CYP2D6-substrate:	0.972
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.394
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.979
HLM stability:	0.959 ? 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):

6.101

Half-life (T1/2):

1.282

ADMET: Toxicity

hERG Blockers:	0.041	hERG Blockers (10um):	0.355
Human Hepatotoxicity (H-HT):	0.425	Drug-induced Liver Injury (DILI):	0.469
AMES Toxicity:	0.789	Rat Oral Acute Toxicity:	0.281
Maximum Recommended Daily Dose:	0.551	Skin Sensitization:	0.973
Carcinogencity:	0.581	Eye Corrosion:	0.687
Eye Irritation:	0.996	Respiratory Toxicity:	0.404
Drug-induced Neurotoxicity:	0.364	Ototoxicity:	0.206
Hematotoxicity:	0.102	Drug-induced Nephrotoxicity:	0.531
Genotoxicity:	0.849	RPMI-8226 Immunitoxicity:	0.088
A549 Cytotoxicity:	0.338	Hek293 Cytotoxicity:	0.391
BCF:	1.125 ? 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:	3.612 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.46 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.801 ? 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
NPO25302	Viola philippica	Species	Violaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14519932]
NPO487	Tabebuia avellanedae	Species	Bignoniaceae	Eukaryota	n.a.	bark	n.a.	PMID[17950604]
NPO487	Tabebuia avellanedae	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17950604]
NPO487	Tabebuia avellanedae	Species	Bignoniaceae	Eukaryota	n.a.	Brazilian	n.a.	PMID[19674905]
NPO28287	Magnaporthe oryzae	Species	Magnaporthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26258762]
NPO487	Tabebuia avellanedae	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32044231]
NPO6773	Bryoria implexa	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4567	Senecio chrysocoma	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO318	Glycosmis trichanthera	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28287	Magnaporthe oryzae	Species	Magnaporthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3641	Polyporus tuberaster	Species	Polyporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16391	Protea neriifolia	Species	Proteaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25302	Viola philippica	Species	Violaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3751	Orthantha lutea	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO487	Tabebuia avellanedae	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25302	Viola philippica	Species	Violaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25302	Viola philippica	Species	Violaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO6773	Bryoria implexa	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4567	Senecio chrysocoma	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO318	Glycosmis trichanthera	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16391	Protea neriifolia	Species	Proteaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3751	Orthantha lutea	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO3641	Polyporus tuberaster	Species	Polyporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28287	Magnaporthe oryzae	Species	Magnaporthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO487	Tabebuia avellanedae	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12083	Hydnellum zonatum	Species	Thelephoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25302	Viola philippica	Species	Violaceae	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

Activity Type	# Activity
Activity	12

Activity Type	# Activity
Organism	12

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
NPT2234	Organism	Convolvulaceae	Convolvulaceae	Activity	=	24.0	mm2	DOI[10.1021/np50077a009]
NPT2236	Organism	Sorghum halepense	Sorghum halepense	Activity	=	34.0	mm2	DOI[10.1021/np50077a009]
NPT2237	Organism	Sorghum	Sorghum	Activity	=	40.0	mm2	DOI[10.1021/np50077a009]
NPT125	Organism	Chenopodium album	Chenopodium album	Activity	=	14.0	mm2	DOI[10.1021/np50077a009]
NPT2232	Organism	Senna obtusifolia	Senna obtusifolia	Activity	=	20.0	mm2	DOI[10.1021/np50077a009]
NPT2233	Organism	Sida spinosa	Sida spinosa	Activity	=	40.0	mm2	DOI[10.1021/np50077a009]
NPT2235	Organism	Datura stramonium	Datura stramonium	Activity	=	24.0	mm2	DOI[10.1021/np50077a009]
NPT2231	Organism	Cornus florida	Cornus florida	Activity	=	7.0	mm2	DOI[10.1021/np50077a009]
NPT2231	Organism	Cornus florida	Cornus florida	Activity	=	14.0	mm2	DOI[10.1021/np50077a009]
NPT2231	Organism	Cornus florida	Cornus florida	Activity	=	10.0	mm2	DOI[10.1021/np50077a009]
NPT2238	Organism	Nasturtium officinale	Nasturtium officinale	Activity	=	36.0	mm2	DOI[10.1021/np50077a009]
NPT2239	Organism	Ambrosia artemisiifolia	Ambrosia artemisiifolia	Activity	=	60.0	mm2	DOI[10.1021/np50077a009]

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 NPC235115 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	20496
0.1-0.2	26283
0.2-0.3	2794
0.3-0.4	219
0.4-0.5	31
0.5-0.6	24
0.6-0.7	8
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
0.6977	Remote Similarity	NPC609111
0.6809	Remote Similarity	NPC609639
0.6122	Remote Similarity	NPC487947
0.6098	Remote Similarity	NPC219892
0.6098	Remote Similarity	NPC214702
0.6098	Remote Similarity	NPC470831
0.6098	Remote Similarity	NPC599777
0.6	Remote Similarity	NPC53649
0.5926	Remote Similarity	NPC221352
0.5909	Remote Similarity	NPC145442
0.5833	Remote Similarity	NPC70380
0.5769	Remote Similarity	NPC764
0.5769	Remote Similarity	NPC487444
0.5714	Remote Similarity	NPC607490
0.56	Remote Similarity	NPC105456
0.56	Remote Similarity	NPC139634
0.5385	Remote Similarity	NPC608268
0.5349	Remote Similarity	NPC488349
0.5349	Remote Similarity	NPC195964
0.5349	Remote Similarity	NPC488354
0.5283	Remote Similarity	NPC191835
0.5283	Remote Similarity	NPC609527
0.5283	Remote Similarity	NPC610163
0.5283	Remote Similarity	NPC611086
0.5273	Remote Similarity	NPC472602
0.5227	Remote Similarity	NPC291454
0.5217	Remote Similarity	NPC610217
0.5185	Remote Similarity	NPC212693
0.5185	Remote Similarity	NPC94248
0.5111	Remote Similarity	NPC470842
0.5091	Remote Similarity	NPC472035
0.5091	Remote Similarity	NPC609495

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC235115 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4527
0.1-0.2	4521
0.2-0.3	97
0.3-0.4	5
0.4-0.5	0
0.5-0.6	0
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
		NPD

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