NPASS Compound

Natural Product: NPC79202

Natural Product ID	NPC79202
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(R)-(+)-Menthofuran
IUPAC Name	(6R)-3,6-dimethyl-4,5,6,7-tetrahydro-1-benzofuran
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3526658
PubChem CID	442478
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001549] Monoterpenoids [CHEMONTID:0000051] Aromatic monoterpenoids

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 26 0 0 0 0 0 0 0 0999 V2000 -3.1957 0.0751 0.4751 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8112 -0.4392 0.0778 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9519 -0.3713 1.3029 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2199 0.5861 1.1716 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9400 0.2000 -0.0635 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2288 -0.1020 -0.4419 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3631 -0.0917 0.5235 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2331 -0.3900 -1.7922 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9979 -0.2656 -2.2058 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1934 0.0801 -1.2309 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2627 0.3607 -1.0888 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4675 0.8806 -0.2383 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9206 -0.7705 0.4309 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1964 0.5131 1.4901 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9182 -1.4924 -0.3119 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5421 -0.1642 2.2231 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4800 -1.3916 1.4193 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2197 1.6030 1.0723 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8331 0.4732 2.0768 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2620 -0.5639 0.0531 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0628 -0.6037 1.4609 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6612 0.9510 0.7586 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1261 -0.6589 -2.3343 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3485 1.4548 -0.8266 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8069 0.1275 -2.0078 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 1 0 5 6 1 0 6 7 1 0 6 8 2 0 8 9 1 0 9 10 1 0 10 11 1 0 11 2 1 0 10 5 2 0 1 12 1 0 1 13 1 0 1 14 1 0 2 15 1 6 3 16 1 0 3 17 1 0 4 18 1 0 4 19 1 0 7 20 1 0 7 21 1 0 7 22 1 0 8 23 1 0 11 24 1 0 11 25 1 0 M END

Standard InCHIKey	YGWKXXYGDYYFJU-SSDOTTSWSA-N
Standard InCHI	InChI=1S/C10H14O/c1-7-3-4-9-8(2)6-11-10(9)5-7/h6-7H,3-5H2,1-2H3/t7-/m1/s1
SMILES	C[C@@H]1CCc2c(C)coc2C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	150.1	Volume:	167.921 ? Van der Waals volume.
Dense:	0.894	LogP:	3.775 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.077 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.978 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	10.0
TPSA:	13.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	1.0
H-Bond Donor:	0.0	Rings:	2.0
Heavy Atoms:	1.0

MedChem Properties

QED Drug-Likeness Score:	0.554	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.337	Fsp³:	0.6
MCE-18:	35.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.054	Fluc inhibitor:	0.32 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.08 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.003 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.879	Promiscuous compounds:	0.021

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.493	MDCK Permeability:	-4.578
Pgp-inhibitor:	0.903	Pgp-substrate:	0.24
PAMPA:	0.035 ? 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):	0.001
20% Bioavailability (F20%):	0.163	30% Bioavailability (F30%):	0.204
50% Bioavailability (F50%):	0.466

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.562	MRP1:	0.947
Plasma Protein Binding (PPB):	84.867%	Volume Distribution (VD):	0.399
Fu:	14.584% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.966	BCRP inhibitor:	0.352
BSEP inhibitor:	0.991

ADMET: Metabolism

CYP1A2-inhibitor:	0.75	CYP1A2-substrate:	0.79
CYP2C19-inhibitor:	0.769	CYP2C19-substrate:	0.47
CYP2C9-inhibitor:	0.923	CYP2C9-substrate:	0.107
CYP2D6-inhibitor:	0.799	CYP2D6-substrate:	0.111
CYP3A4-inhibitor:	0.853	CYP3A4-substrate:	0.847
CYP2B6-substrate:	0.789	CYP2C8-inhibitor:	0.834
HLM stability:	0.551 ? 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):

9.303

Half-life (T1/2):

0.663

ADMET: Toxicity

hERG Blockers:	0.116	hERG Blockers (10um):	0.371
Human Hepatotoxicity (H-HT):	0.484	Drug-induced Liver Injury (DILI):	0.582
AMES Toxicity:	0.652	Rat Oral Acute Toxicity:	0.465
Maximum Recommended Daily Dose:	0.662	Skin Sensitization:	0.468
Carcinogencity:	0.903	Eye Corrosion:	0.663
Eye Irritation:	0.992	Respiratory Toxicity:	0.725
Drug-induced Neurotoxicity:	0.165	Ototoxicity:	0.207
Hematotoxicity:	0.284	Drug-induced Nephrotoxicity:	0.192
Genotoxicity:	0.138	RPMI-8226 Immunitoxicity:	0.051
A549 Cytotoxicity:	0.262	Hek293 Cytotoxicity:	0.25
BCF:	2.648 ? 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:	4.068 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.748 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.711 ? 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
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12350137]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	rhizome	n.a.	n.a.	PMID[12617587]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	Rhizomes	n.a.	n.a.	PMID[23153397]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	leaf	n.a.	PMID[23901173]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28068085]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9584408]
NPO1880	Schizonepeta tenuisfolia	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8789	Schizonepeta tenuifolia	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	Root	n.a.	n.a.	Database[FooDB]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	Rhizome Essent. Oil	n.a.	n.a.	Database[FooDB]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	Rhizome	n.a.	n.a.	Database[FooDB]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	Essential Oil	n.a.	n.a.	Database[FooDB]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO8789	Schizonepeta tenuifolia	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.		Database[Phenol-Explorer]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8789	Schizonepeta tenuifolia	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8789	Schizonepeta tenuifolia	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8789	Schizonepeta tenuifolia	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO1880	Schizonepeta tenuisfolia	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO24124	Curcuma longa	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO8789	Schizonepeta tenuifolia	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24124	Curcuma longa	Species	Zingiberaceae	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
Ki	2
Kd	2

Activity Type	# Activity
Individual protein	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT240	Individual protein	Cytochrome P450 2A6	Homo sapiens	Ki	=	2000.0	nM	PMID[22696418]
NPT240	Individual protein	Cytochrome P450 2A6	Homo sapiens	Kd	=	4500.0	nM	PMID[22696418]
NPT2599	Individual protein	Cytochrome P450 2A13	Homo sapiens	Kd	=	580.0	nM	PMID[22696418]
NPT2599	Individual protein	Cytochrome P450 2A13	Homo sapiens	Ki	=	54000.0	nM	PMID[22696418]

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 NPC79202 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	41098
0.1-0.2	8558
0.2-0.3	187
0.3-0.4	13
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	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC59035

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC79202 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6900
0.1-0.2	2223
0.2-0.3	27
0.3-0.4	0
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