NPASS Compound

Natural Product: NPC276111

Natural Product ID	NPC276111
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	1-(2,6-Dihydroxyphenyl)Butan-1-One
IUPAC Name	1-(2,6-dihydroxyphenyl)butan-1-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3274339
PubChem CID	4090226
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0001831] Carbonyl compounds [CHEMONTID:0000118] Ketones [CHEMONTID:0003670] Aryl ketones [CHEMONTID:0004296] Phenylketones [CHEMONTID:0004298] Alkyl-phenylketones

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 25 25 0 0 0 0 0 0 0 0999 V2000 -3.2094 0.3259 -0.7689 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7490 0.1840 -0.3999 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7018 -0.3180 1.0473 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2975 -0.4876 1.4976 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1315 -0.8976 2.6756 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8541 -0.2091 0.6622 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4588 1.0319 0.6117 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5607 1.2413 -0.2079 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0909 0.2383 -0.9936 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4839 -0.9988 -0.9398 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3762 -1.2194 -0.1195 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7697 -2.4736 -0.0722 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9231 2.0335 1.4013 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6846 -0.6641 -0.5674 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3554 0.5854 -1.8276 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6876 1.0503 -0.0766 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2974 -0.6291 -1.0112 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1947 1.1222 -0.4797 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1840 -1.3145 1.1224 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2415 0.3945 1.7026 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0237 2.2211 -0.2361 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9513 0.4152 -1.6288 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8742 -1.7966 -1.5392 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4603 -2.8396 -0.9772 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9076 3.0044 1.1249 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 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 7 13 1 0 11 6 1 0 1 14 1 0 1 15 1 0 1 16 1 0 2 17 1 0 2 18 1 0 3 19 1 0 3 20 1 0 8 21 1 0 9 22 1 0 10 23 1 0 12 24 1 0 13 25 1 0 M END

Standard InCHIKey	GMFURTWBEPILKH-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C10H12O3/c1-2-4-7(11)10-8(12)5-3-6-9(10)13/h3,5-6,12-13H,2,4H2,1H3
SMILES	CCCC(=O)c1c(cccc1O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	180.08	Volume:	188.785 ? Van der Waals volume.
Dense:	0.954	LogP:	2.898 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.88 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.729 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	7.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	1.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.7	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.09	Fsp³:	0.3
MCE-18:	7.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.116	Fluc inhibitor:	0.038 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.279 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.052 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.956	Promiscuous compounds:	0.262

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.481	MDCK Permeability:	-4.604
Pgp-inhibitor:	0.394	Pgp-substrate:	0.102
PAMPA:	0.227 ? 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):	0.01
20% Bioavailability (F20%):	0.029	30% Bioavailability (F30%):	0.172
50% Bioavailability (F50%):	0.653

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.697	MRP1:	0.845
Plasma Protein Binding (PPB):	88.562%	Volume Distribution (VD):	-0.165
Fu:	8.855% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.837
OATP1B3 inhibitor:	0.971	BCRP inhibitor:	0.192
BSEP inhibitor:	0.838

ADMET: Metabolism

CYP1A2-inhibitor:	0.987	CYP1A2-substrate:	0.841
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.999
CYP2C9-inhibitor:	0.398	CYP2C9-substrate:	0.023
CYP2D6-inhibitor:	0.041	CYP2D6-substrate:	0.128
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.416
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.989 ? 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):

4.615

Half-life (T1/2):

1.136

ADMET: Toxicity

hERG Blockers:	0.027	hERG Blockers (10um):	0.56
Human Hepatotoxicity (H-HT):	0.206	Drug-induced Liver Injury (DILI):	0.073
AMES Toxicity:	0.439	Rat Oral Acute Toxicity:	0.398
Maximum Recommended Daily Dose:	0.289	Skin Sensitization:	0.737
Carcinogencity:	0.356	Eye Corrosion:	0.688
Eye Irritation:	0.996	Respiratory Toxicity:	0.975
Drug-induced Neurotoxicity:	0.208	Ototoxicity:	0.109
Hematotoxicity:	0.227	Drug-induced Nephrotoxicity:	0.148
Genotoxicity:	0.31	RPMI-8226 Immunitoxicity:	0.074
A549 Cytotoxicity:	0.306	Hek293 Cytotoxicity:	0.331
BCF:	0.846 ? 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:	3.512 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.669 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.972 ? 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
NPO996	Acacia confusa	Species	Fabaceae	Eukaryota	leaves	n.a.	n.a.	PMID[10843598]
NPO996	Acacia confusa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20047272]
NPO5664	Davallia mariesii	Species	Davalliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2851	Acanthella acuta	Species	Axinellidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO996	Acacia confusa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1919	Erica arborea	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4725	Isodon lihsienensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5664	Davallia mariesii	Species	Davalliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1919	Erica arborea	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5664	Davallia mariesii	Species	Davalliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1919	Erica arborea	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4725	Isodon lihsienensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1919	Erica arborea	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO5664	Davallia mariesii	Species	Davalliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO996	Acacia confusa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6619	Phoebe clemensii	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1919	Erica arborea	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2851	Acanthella acuta	Species	Axinellidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO66	Siphula decumbens	Species	Icmadophilaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4725	Isodon lihsienensis	Species	Lamiaceae	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
IC50	2
Activity	4

Activity Type	# Activity
Others	2
Cell line	2
Organism	2

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
NPT2	Others	Unspecified	n.a.	IC50	=	210000.0	nM	PMID[926120]
NPT2	Others	Unspecified	n.a.	IC50	=	50000.0	nM	PMID[926120]
NPT28949	Cell line	Mesenchymal stem cells	Homo sapiens	Activity	n.a.	n.a.	n.a.	PMID[36475432]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	218.0	%	PMID[926120]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	141.0	%	PMID[926120]

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 NPC276111 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	19542
0.1-0.2	26330
0.2-0.3	3735
0.3-0.4	223
0.4-0.5	18
0.5-0.6	5
0.6-0.7	1
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8571	High Similarity	NPC600129
0.8	Intermediate Similarity	NPC121259
0.6923	Remote Similarity	NPC118288
0.5641	Remote Similarity	NPC195262
0.5429	Remote Similarity	NPC149246
0.5366	Remote Similarity	NPC188814
0.5366	Remote Similarity	NPC608141
0.5238	Remote Similarity	NPC196976

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC276111 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3426
0.1-0.2	5423
0.2-0.3	294
0.3-0.4	6
0.4-0.5	1
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